New Drug Approval -

FDA Grants Accelerated Approval to Novartis’ Vanrafia (Atrasentan): First and Only Endothelin-1 Receptor Blocker for Proteinuria Reduction in IgA Nephropathy (IgAN)

May 19, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Written by: Priyanka Khamkar (M. Pharm., Pharmacology) and Sakshi Thakare (M. Pharm., Pharmacology)

The U.S. Food and Drug Administration (FDA) have granted accelerated approval to Novartis Pharmaceuticals Corporation for Vanrafia (atrasentan). It is a potent and highly selective Endothelin A (ETA) receptor antagonist. This once-daily, oral, non-steroidal medication is approved to reduce proteinuria in adults with primary Immunoglobulin A nephropathy (IgAN) who are at high risk of rapid disease progression. Disease progression typically indicated by a urine protein-to-creatinine ratio (UPCR) of ≥1.5 g/g. Vanrafia is intended for use alongside standard supportive treatments, including renin-angiotensin system (RAS) inhibitors, with or without sodium-glucose co-transporter-2 (SGLT2) inhibitors. FDA approved Vanrafia under accelerated approval based on reduction of proteinuria and it has not been confirmed yet that it slows kidney function decline in patient with IgAN. The confirmatory trial results and clinical benefits will be verified to continue this approval. This approval marks a significant advancement in the treatment of IgAN, a chronic kidney disease that can lead to kidney failure in up to 50% of patients within 10 to 20 years of diagnosis.

What is IgAN?

Immunoglobulin A (IgA) nephropathy, also known as IgAN or Berger’s disease, is one of the most common causes of glomerulonephritis and can lead to kidney failure. This widespread kidney disorder is marked by the build-up of IgA antibodies in the glomerular basement membrane, which triggers immune-related damage where the immune system attacks the kidneys. Clinically, it is commonly seen as blood in the urine (hematuria), protein in the urine (proteinuria), and a gradual decline in kidney function. On histological examination, a range of changes in the glomeruli might be observed, with mesangial cell proliferation and prominent IgA deposits being the most notable features.

In IgA nephropathy (IgAN), the accumulation of IgA in the kidneys happens due to a problem with how the body produces and handles a specific type of antibody called IgA1. It all started when the body produced an abnormal form of IgA1, known as galactose-deficient IgA1 (Gd-IgA1), which has a faulty sugar moiety attached to it. The immune system recognized this altered IgA1 as abnormal and generated autoantibodies that bind to it, forming immune complexes in the bloodstream.

These immune complexes travel to the kidneys and become deposited in the mesangium the central part of the glomeruli, which are the kidneys’ filtering units. This deposition triggers inflammation and immune-mediated injury, progressively damaging the kidney tissue. Over time, this leads to symptoms such as blood in the urine (hematuria), protein in the urine (proteinuria), and a gradual decline in kidney function. Due to this self-directed immune response, IgAN is considered an autoimmune-like kidney disease.

Background and Need for New Treatments

Conventional treatment for IgA nephropathy primarily involves supportive care, including blood pressure control and the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to reduce proteinuria. However, these approaches are not very successful in significantly extending the progression of chronic kidney disease (CKD) to end-stage renal disease.

The role of sodium–glucose co transporter 2 (SGLT2) inhibitors in IgA nephropathy is not yet fully understood. Although nonspecific immunosuppressive treatments such as systemic or enteric-coated glucocorticoids have shown some benefit in high-risk patients, these effects are often not sustained without continued therapy. Long-term use is limited due to safety concerns and adverse side effects. As a result, there is a need for a safe and targeted therapy specifically for IgAN that can reliably slow disease progression in patients with IgA nephropathy.

Vanrafia (atrasentan): A Novel Approach

Vanrafia (atrasentan) is a once-daily, non-steroidal oral medication approved for adults with primary Immunoglobulin A Nephropathy (IgAN) to help lower protein levels in the urine (proteinuria), especially in those at high risk of fast disease progression. It works by blocking the Endothelin A (ETA) receptor, a key part of the pathway that contributes to kidney damage.

Endothelin-1 (ET-1) is elevated in IgA nephropathy (IgAN) due to ongoing inflammation and injury in the kidneys triggered by immune complex deposition. This immune activation leads to the release of various pro-inflammatory molecules, such as TNF-alpha, IL-6, TGF-beta, these substances stimulate the local production of endothelin-1 by endothelial and mesangial cells in the kidneys. Once produced, ET-1 worsens kidney injury by constricting blood vessels, reducing blood flow and oxygen to kidney tissue (ischemia), promoting mesangial cell proliferation and matrix expansion, increasing inflammation and fibrosis, and enhancing protein leakage into urine (proteinuria). This entire process is mediated by activation of Endothelin Type A Receptor (ETAR), a protein found on kidney cells. Vanrafia belongs to a class of drugs known as ETA receptor antagonists. It works by selectively blocking the ETAR, thereby helping to protect kidney function and reduce proteinuria in patients with IgAN. This unique mechanism makes Vanrafia a specific drug of choice that selectively acts on the actual cause of the IgAN.

Clinical Trials and Approval

The efficacy and safety of Vanrafia is being studied in ALIGN trial (NCT04573478), is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of atrasentan in patients with IgA nephropathy (IgAN) at risk of progressive loss of renal function. Participants receive either 0.75 mg of atrasentan or a placebo daily for 132 weeks. An open-label extension allows eligible participants to receive atrasentan for an additional 48 weeks. All participants are required to be on a stable dose of a renin-angiotensin system (RAS) inhibitor, unless contraindicated. A separate cohort includes participants on a stable dose of a sodium-glucose co-transporter-2 inhibitor (SGLT2) who have been under study. The primary endpoint of the trial is the change in proteinuria as measured by the urine protein-to-creatinine ratio (UPCR). Secondary endpoints include change in kidney function over time as measured by eGFR, safety and tolerability assessments, and quality of life evaluations.

The interim results of the Phase 3 ALIGN trial were presented at the European Reanl Association (ERA) Congress in May 2024. In the prespecified interim analysis involving 270 patients (135 per group), atrasentan achieved a 36.1% greater reduction in 24-hour urinary protein-to creatinine ratio (UPCR) compared to placebo at week 36. Specifically, the geometric mean percentage change from baseline was 38.1% in the atrasentan group versus 3.1% in the placebo group. This reduction in proteinuria is clinically meaningful, as persistent proteinuria is associated with a higher risk of progression to kidney failure in IgAN patients.

Based on these interim results, Novartis submitted an application to the U.S. Food and Drug Administration (FDA) for accelerated approval of atrasentan. In May 2025, the FDA granted accelerated approval for atrasentan based on the condition of verification of the final results of the ALIGN study, which will serve as a confirmatory trial

Safety profile

Vanrafia exhibited a favourable safety profile consistent with previously reported data. The most frequently observed adverse events (occurring in ≥2% of patients and more often than with placebo) included peripheral edema, anemia, and elevated liver transaminases. Given the potential for hepatotoxicity associated with certain endothelin receptor antagonists, liver function should be assessed before initiating Vanrafia and monitored throughout treatment as clinically indicated.

Vanrafia is strictly contraindicated during pregnancy due to the risk of serious birth defects. Pregnancy must be ruled out before starting treatment with Vanrafia. Patients should be advised to use effective contraception before beginning therapy, throughout treatment, and for at least two weeks after discontinuing Vanrafia. If a patient becomes pregnant while on Vanrafia, the medication should be discontinued as soon as possible.

Conclusion

The FDA’s accelerated approval of Vanrafia represents a significant milestone in the management of primary IgA nephropathy. With its demonstrated efficacy in reducing proteinuria and favorable safety profile, Vanrafia offers a promising new option for patients at risk of rapid disease progression. As ongoing studies continue to evaluate its long-term benefits, Vanrafia may play a crucial role in transforming the care of individuals living with IgAN.

References

Novartis receives FDA accelerated approval for Vanrafia® (atrasentan), the first and only selective endothelin A receptor antagonist for proteinuria reduction in primary IgA nephropathy (IgAN), Novartis, https://www.novartis.com/news/media-releases/novartis-receives-fda-accelerated-approval-vanrafia-atrasentan-first-and-only-selective-endothelin-receptor-antagonist-proteinuria-reduction-primary-iga-nephropathy-igan

Heerspink HJL, Jardine M, Kohan DE, Lafayette RA, Levin A, Liew A, Zhang H, Lodha A, Gray T, Wang Y, Renfurm R, Barratt J; ALIGN Study Investigators. Atrasentan in Patients with IgA Nephropathy. N Engl J Med. 2025 Feb 6;392(6):544-554. doi: 10.1056/NEJMoa2409415. Epub 2024 Oct 25. PMID: 39460694.

Rout P, Limaiem F, Hashmi MF. IgA Nephropathy (Berger Disease) [Updated 2024 Apr 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538214/

Highlights of Prescribing Information, VANRAFIA (atrasentan), https://www.novartis.com/us-en/sites/novartis_us/files/vanrafia.pdf

FDA Grants Accelerated Approval for Vanrafia (atrasentan) for Proteinuria Reduction in Primary IgA Nephropathy, Drugs.com, https://www.drugs.com/newdrugs/fda-grants-accelerated-approval-vanrafia-atrasentan-proteinuria-reduction-primary-iga-nephropathy-6493.html

Floege J, Rauen T, Tang SCW. Current treatment of IgA nephropathy. Semin Immunopathol. 2021 Oct;43(5):717-728. Doi: 10.1007/s00281-021-00888-3. Epub 2021 Sep 8. PMID: 34495361; PMCID: PMC8551131.

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FDA Approves Imaavy (nipocalimab-aahu), a Neonatal Fc Receptor (FcRn) Blocker, Offering New Hope for People Living with Generalized Myasthenia Gravis (gMG)

May 19, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Written by Priya Bhaware (M.Pharm. Pharmacology)

The Food and Drug Administration approved Imaavy (Nipocalimab-aahu) for the treatment of generalized myasthenia gravis (gMG) in adult and paediatric patients 12 years of age and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. Imaavy is a monoclonal antibody that functions as a neonatal Fc receptor (FcRn) blocker. Imaavy is developed by Johnson & Johnson and is the first treatment of its kind. It offers a new option for both adolescent and adult patients living with generalized myasthenia gravis, aiming to reduce symptoms and improve daily life.

Background and Need for New Treatments

Generalized Myasthenia Gravis (gMG) is a rare and chronic autoimmune disorder that leads to muscle weakness, making simple daily activities such as lifting your arms, chewing, swallowing, or even breathing feel extremely strenuous. The condition occurs when the immune system mistakenly attacks the neuromuscular junction and disrupts the communication pathway between nerves and muscles. This immune response, often involving harmful antibodies that target proteins like AChR or MuSK, interferes with the brain’s ability to send signals to the muscles, resulting in reduced muscle function.

Current treatments of myasthenia gravis include acetylcholinesterase inhibitors, corticosteroids, immunosuppressive drugs, plasmapheresis, plasma exchange, and intravenous immunoglobulin (IVIG). While conventional treatments can control symptoms and improve quality of life, they often come with significant side effects, invasive procedures, delayed action, flare-ups, or only temporary relief. Thus, there is a real need for more targeted and gentler treatment options, and this need and limitation have led to the development of newer, targeted therapies like monoclonal antibodies (e.g., eculizumab, ravulizumab) that aim for more precise immune modulation with fewer systemic effects, and Imaavy (nipocalimab) is the latest addition to this list of monoclonal antibodies.

Imaavy (nipocalimab-aahu): A Novel Approach

Imaavy is a targeted therapy developed to reduce specific pathogenic IgG antibodies associated with myasthenia gravis without suppressing the entire immune system. For patients who have not achieved adequate symptom control with conventional therapies, Imaavy provides a more precise mechanism of action that may improve symptom management and enhance daily functioning and quality of life.

The treatment was initially discovered by Momenta Pharmaceuticals, Inc., and subsequently licensed to Janssen Biotech, NC., a subsidiary of Johnson & Johnson, for further development and commercialization.

Imaavy exerts its therapeutic effect by binding with high affinity to the neonatal Fc receptor (FcRn) under both acidic and neutral pH conditions. This interaction prevents the recycling of IgG antibodies including the autoantibodies implicated in myeasthenia gravis leading to their accelerated degradation and substantial reduction in total circulating IgG levels.

Clinical Trials and Approval

The U.S. Food and Drug Administration (FDA) approved Imaavy based on robust efficacy and safety data from the Phase 3 Vivacity-MG3 trial (NCT04951622), supported by findings from the ongoing Vibrance-MG pediatric study (NCT05265273).

In the Vivacity-MG3 trial, 199 adults with generalized myasthenia gravis (gMG), including both antibody-positive and antibody-negative patients inadequately controlled by existing standard therapies, were randomized to receive either nipocalimab (30 mg/kg IV loading dose followed by 15 mg/kg every two weeks) in combination with standard of care or placebo plus standard of care.

Nipocalimab demonstrated clinically meaningful benefits, including a statistically significant improvement in Myasthenia Gravis–Activities of Daily Living (MG-ADL) scores. Over the 24-week treatment period, patients receiving nipocalimab experienced an average -4.70 point improvement in MG-ADL scores, compared to -3.35 points in the placebo group.

The clinical trial (NCT05265273), known as the Vibrance-MG study, is an ongoing Phase 2/3 open-label trial evaluating the safety, pharmacokinetics, and efficacy of nipocalimab in pediatric patients aged 2 to less than 18 years with generalized myasthenia gravis (gMG). The study aims to assess the effect of nipocalimab on total serum immunoglobulin G (IgG) levels, safety and tolerability, and pharmacokinetics in this population. Participants receive intravenous infusions of nipocalimab every two weeks during a 24-week active treatment phase, followed by a long-term extension phase and an 8-week safety follow-up. The primary outcome measures include changes in total serum IgG levels, while secondary endpoints assess improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.

The result of these two trials underscore Imaavy’s potential as a targeted and effective treatment option for adults and adolescents (ongoing) living with generalized myasthenia gravis

Safety Profile

Most reported adverse events (AEs) were mild to moderate in severity. The most commonly reported adverse reactions (occurring in ≥10% of patients) in individuals with generalized myasthenia gravis treated with Imaavy were respiratory tract infections, peripheral edema, and muscle spasms. Serious side effects and treatment discontinuations were less common in the group receiving nivolumab than in those receiving placebo.

Patients receiving Imaavy should be monitored for infections, and administration should be delayed in those with active infections. If a serious infection develops during treatment, appropriate therapy should be initiated, and Imaavy should be withheld until the infection resolves.

Hypersensitivity reactions such as angioedema, anaphylaxis, rash, urticaria, and eczema have been reported with Imaavy. If such a reaction occurs, the infusion should be discontinued immediately, and appropriate medical management should be provided.

In the event of a severe infusion-related reaction, treatment with Imaavy should be stopped, and appropriate intervention should be initiated. Re-administration should only be considered after carefully weighing the risks and benefits. If a mild to moderate infusion-related reaction occurs, rechallenging may be considered with close monitoring, slower infusion rates, and premedication to minimize recurrence.

Conclusion

The approval of imaavy represents a significant advancement in addressing the complex challenges of autoimmune diseases such as generalized myasthenia gravis. By specifically targeting and reducing pathogenic IgG antibodies that interfere with nerve-to-muscle communication, Imaavy provides a novel and focused treatment option for patients whose symptoms are not adequately managed by current therapies.

In essence, imaavy targeted mechanism of action offers new hope for individuals living with gMG, particularly those who have not responded well to conventional treatments. Furthermore, its potential applicability to a broader range of autoimmune conditions underscores its versatility and the meaningful impact it may have within the field of immunology.

References

IMAAVY™ (nipocalimab-aahu) approved by FDA for treatment of Myasthenia Gravis (gMG) in ) in people aged 12 and older who test positive for AChR or MuSK antibodies, April 30, 2025, available from https://www.prnewswire.com/news-releases/johnson–johnson-receives-fda-approval-for-imaavy-nipocalimab-aahu-a-new-fcrn-blocker-offering-long-lasting-disease-control-in-the-broadest-population-of-people-living-with-generalized-myasthenia-gravis-gmg-302442650.html

Dresser L, Wlodarski R, Rezania K, Soliven B. Myasthenia gravis: epidemiology, pathophysiology and clinical manifestations. Journal of clinical medicine. 2021 May 21;10(11):2235.

IMAAVY™ (nipocalimab-aahu),Highlights of Prescribing Information, available from https://www.drugs.com/imaavy.html

Nipocalimab pivotal Phase 3 trial demonstrates longest sustained disease control in FcRn class. Johnson & Johnson. June 28, 2024. https://www.jnj.com/media-center/press-releases/nipocalimab-pivotal-phase-3-trial-demonstrates-longest-sustained-disease-control-in-fcrn-class

Nipocalimab demonstrates sustained disease control in adolescents living with generalized myasthenia gravis in Phase 2/3 study. Johnson & Johnson. October 15, 2024. https://www.jnj.com/media-center/press-releases/nipocalimab-demonstrates-sustained-disease-control-in-adolescents-living-with-generalized-myasthenia-gravis-in-phase-2-3-study

Highlights of Prescribing Information, Imaavy (nipocalimab-aahu) injection, https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761430s000lbl.pdf

Antozzi C, Vu T, Ramchandren S, et al, Vivacity-MG3 Study Group. Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2025 Feb;24(2):105-116. Doi: 10.1016/S1474-4422(24)00498-8. PMID: 39862879.

A Study of Nipocalimab in Children Aged 2 to Less Than 18 Years With Generalized Myasthenia Gravis, All clinical trials, NCT05265273, https://www.allclinicaltrials.com/study/NCT05265273

The article is extensively reviewed and fact-checked by the editorial team of pharmacally.com

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FDA Approval of Atzumi Marks a New Era in Migraine Treatment with SMART MucoAdhesive Delivery

May 19, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Written by: Utkarsha Patil (M.Pharm., Pharmacology) and Shakuntala Kawhale (M.Pharm., Pharmacology)

The U.S. Food and Drug Administration (FDA) have approved Atzumi (dihydroergotamine mesylate) nasal powder for the acute treatment of adult migraine with or without aura, marking a major breakthrough in migraine care. This approval offers millions of migraine sufferers’ quick and efficient relief by introducing a new, non-invasive delivery method for a proven migraine medication. However the approval comes with some limitations like it is not indicated for preventive treatment of migraine or for the management of hemiplegic migraine or migraine with brainstem aura. Satsuma pharmaceuticals are known for their innovative products have been given this landmark approval by FDA. Atzumi has been developed on the SMART platform (Simple Mucoadhesive Release Technology) which uses to combines a proprietary advanced powder and device technology to simplify delivery of medicine.

Migraine and Need of the Novel Therapy

Migraine is defined as a severe, throbbing, and unilateral headache that is usually associated with photophobia (light sensitivity), phonophobia (sound sensitivity), nausea, and vomiting. It is generally considered a neurological disorder that comes in episodic attacks or presents in chronic form with or without aura.

Conventional therapy for migraine includes acute and preventive (prophylactic) treatment with various drug classes used depending on the frequency and severity of attacks. Like NSAIDs, triptans, ergotamines, and antiemetics. Preventive therapy includes anti-seizure drugs, beta-blockers, calcium channel blockers, antidepressants, and Botox treatment.

Despite the availability of numerous medicines and these medicine have effect to minimise migraine to some extent, many patients still suffer from terrible side effects, treatment failure, or delayed relief.

Triptans, one of the most commonly prescribed classes, act as serotonin receptor agonists and work by causing vasoconstriction. However, this mechanism makes them unsuitable for individuals with cardiovascular disease. They are most effective when taken early during a migraine attack but can cause side effects such as dizziness, fatigue, and nausea. Additionally, frequent use can lead to rebound headaches or medication-overuse headaches (MOH).

NSAIDs are often used to relieve mild to moderate migraine pain, but they are typically ineffective for more severe attacks. Prolonged or frequent use can result in gastrointestinal complications, including ulcers and bleeding.

Antiemetics, which are used to alleviate nausea associated with migraines, can cause extrapyramidal symptoms such as dystonia and akathisia. They may also lead to sedation and, with long-term use, carry a risk of tardive dyskinesia.

Although Dihydroergotamine (DHE) has been used for decades to treat migraine attacks, it is associated with poor tolerability, variable absorption, and serious side effects like vasospasm and ischemia. Their use requires careful dosing to avoid toxicity.

Atzumi: A Novel Powdered Nasal Ingredient

FDA is approved Atzumi is a powdered nasal inhaler that delivers dihydroergotamine mesylate (DHE) in the form of a dry nasal powder. It provides migraineurs with a quick-acting, convenient, and needle-free alternative. Atzumi harbour various advantages over its older form of dosage and also over other therapies which includes Innovative Delivery System where it utilizes the SMART (Simple MucoAdhesive Release Technology) platform, combining advanced powder formulation with a proprietary nasal delivery device. This system ensures consistent and accurate dosing, enhancing drug absorption and patient convenience. Rapid and Sustained Absorption: Clinical studies demonstrated that Atzumi achieves rapid absorption, with mean DHE plasma concentrations of 2.0 ng/mL within approximately 15 to 20 minutes. This rapid onset is coupled with sustained plasma levels, providing prolonged relief from migraine symptoms. Improved Tolerability: Compared to injectable and liquid nasal spray forms, Atzumi’s dry powder formulation reduces issues like nasal dripping and throat irritation. Common adverse events were generally mild, including rhinitis, nausea, and altered taste. Ease of Use: The portable, single-use device allows for self-administration without the need for refrigeration, making it more accessible for patients. Non-Oral Administration: By bypassing the gastrointestinal tract, Atzumi avoids issues related to nausea and vomiting that can come with migraines, which often hinder the effectiveness of oral medications. Suitable for Triptan Non-Responders: For patients who do not respond to or cannot tolerate triptans, Atzumi provides an alternative with a different mechanism of action.

Hence, the approval of Atzumi marks an important milestone, offering a new option for the acute treatment of migraine that blends the long-established effectiveness of DHE with a user-friendly, convenient delivery system.

Ryoichi Nagata, Satsuma Pharmaceuticals said in a statement. “We believe that Atzumi will contribute to improving the quality of life of patients struggling for relief from these highly disabling problems.”

FDA Approval and Evidence from Clinical Trials

Even though DHE is in practice since long, Atzumi approval comes from rigorous clinical trials in which DHE underwent A Phase 1 pharmacokinetics (PK) trial and the Phase 3 open-label trials called ASCEND Trial, aassessed the long-term safety and tolerability of Atzumi in adults with migraine.

Phase 1 study (NCT03874832), is randomized, open-label, three-period crossover study that evaluated the pharmacokinetics, safety, and tolerability of STS101 (Atzumi), a dihydroergotamine (DHE) nasal powder, in 43 healthy adult volunteers. The study compared single doses of STS101 with intravenous (IV) DHE and DHE nasal spray, aiming to assess parameters like maximum plasma concentration (C_max) and time to reach maximum concentration (T_max). STS101 demonstrated rapid absorption, reaching effective plasma levels within 10 minutes, and achieved higher bioavailability than the DHE nasal spray. It also showed a favorable safety profile, with lower C_max than IV DHE, reducing the risk of nausea. These promising results supported the advancement of STS101 into later-phase trials, including the Phase 3 ASCEND study (NCT04406649).

The ASCEND trial (NCT04406649) was a Phase 3, open-label, multicenter study evaluating the long-term safety, tolerability, and exploratory efficacy of STS101 (Atzumi), for the acute treatment of migraine in adults aged 18 to 65 years. Participants with a history of migraine with or without aura self-administered STS101 as needed over a 12-month period, with some continuing up to 18 months. The study found that STS101 was well tolerated, with a low incidence of treatment-emergent adverse events (TEAEs), most of which were mild or moderate. Efficacy assessments showed that 36.6% of treated attacks achieved pain freedom at 2 hours post-dose, increasing to 85.5% at 24 hours. Additionally, freedom from the most bothersome symptom was reported in 54.3% of attacks at 2 hours, rising to 91.3% at 24 hours. The favorable safety and efficacy profiles observed in the ASCEND trial supported the FDA approval of Atzumi for the acute treatment of migraine with or without aura in adults.

Safety Profile

During clinical trials Atzumi shows common adverse reactions (incidence > 1%) including rhinitis, nausea, altered sense of taste, application site reactions, dizziness, vomiting, somnolence, pharyngitis, and diarrhea. However Atzumi carries a warning of serious drug interaction with strong CYP3A4 inhibitors where serious and potentially life-threatening peripheral ischemia has been linked to the combined use of dihydroergotamine and strong CYP3A4 inhibitors. These inhibitors can raise dihydroergotamine blood levels, increasing the risk of vasospasm, which may lead to cerebral or limb ischemia. Therefore, Atzumi should not be used in combination with strong CYP3A4 inhibitors.

Conclusion

Atzumi approval marks a significant advancement in migraine therapy by addressing the limitations of conventional DHE formulations. Unlike intravenous DHE, which requires administration in clinical settings and is often associated with nausea, or nasal sprays with inconsistent absorption, Atzumi delivers rapid, consistent, and sustained drug levels through a user-friendly nasal powder system. However, due to the risk of vasospasm and ischemia, Atzumi is contraindicated in patients taking strong CYP3A4 inhibitors, which can elevate DHE plasma concentrations. Overall, Atzumi provides an effective, non-invasive, and well-tolerated treatment alternative for patients seeking fast and reliable relief from migraine attacks, with clear advantages over traditional DHE therapies.

Referances

Satsuma Pharmaceuticals (2025, April 30). Satsuma Pharmaceuticals Announces U.S. FDA Approval for Atzumi™ (Dihydroergotamine) Nasal Powder for the Acute Treatment of Migraine. [News Release]. Retrieved May 2025 https://investors.satsumarx.com/2025-04-30-Satsuma-Pharmaceuticals-Announces-U-S-FDA-Approval-for-Atzumi-TM-Dihydroergotamine-Nasal-Powder-for-the-Acute-Treatment-of-Migraine

Burch R. (2024). Acute Treatment of Migraine. Continuum (Minneap Minn), 30(2), 344–363. https://doi.org/10.1212/CON.0000000000001402. PMID: 38568487.

Villar-Martinez MD, Goadsby PJ. (2022). Pathophysiology and Therapy of Associated Features of Migraine. Cells, 11(17), 2767. https://doi.org/10.3390/cells11172767. PMID: 36078174; PMCID: PMC9455236

U.S. Food & Drug Administration (FDA). (2025). Drugs@FDA: FDA-Approved Drugs – Atzumi (Dihydroergotamine Mesylate). https://www.accessdata.fda.gov

Satsuma Pharmaceuticals. (2025). Product Pipeline and Clinical Trial Data – Atzumi https://www.satsumarx.com/pipeline

Johra Khan, Lubna Ibrahim Al Asoom, et al, Genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine, Biomedicine & Pharmacotherapy, Volume 139, 2021, 111557, https://doi.org/10.1016/j.biopha.2021.111557

Albrecht D, Iwashima M, Dillon D, Harris S, Levy J. A Phase 1, Randomized, Open-Label, Safety, Tolerability, and Comparative Bioavailability Study of Intranasal Dihydroergotamine Powder (STS101), Intramuscular Dihydroergotamine Mesylate, and Intranasal DHE Mesylate Spray in Healthy Adult Subjects. Headache. 2020 Apr; 60(4):701-712. Doi: 10.1111/head.13737. Epub 2020 Jan 27. PMID: 31985049; PMCID: PMC7154716.

Tepper SJ, Albrecht D, Ailani J, Kirby L, Strom S, Rapoport AM. Long-Term (12-Month) Safety and Tolerability of STS101 (Dihydroergotamine Nasal Powder) in the Acute Treatment of Migraine: Data from the Phase 3 Open-Label ASCEND Study. CNS Drugs. 2024 Dec; 38(12):1017-1027. Doi: 10.1007/s40263-024-01118-8. Epub 2024 Oct 7. PMID: 39373843; PMCID: PMC11543709.

The article is extensively reviewed and fact-checked by editorial team of pharmacally.com

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FDA Approves PD-1 Inhibitor Penpulimab-kcqx for Advanced Nasopharyngeal Carcinoma (NPC)

May 17, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Written By: Samiksha Benke (M.Pharm., Pharmacology) and Dr. Vinay Manocha (Pharm.D)

In the landmark development, U.S. Food and Drug Administration have approved innovative PD-1 monoclonal antibody, penpulimab-kcqx, in combination with cisplatin or carboplatin and gemcitabine for the initial treatment of adult recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). Penpulimab-kcqx has also been approved as a monotherapy for adult metastatic non-keratinizing NPC in patients who had progression on or after platinum-based therapy and have at least one previous line of treatment. The Food and Drug Administration has approved Penpulimab to Akeso Biopharma Co. Ltd..

Present Data and Background

Based on the WHO 2020 Global Cancer Statistics, more than 133,000 new cases of NPC occur each year worldwide, and more than 70% of the patients have locally advanced disease. Recurrent or metastatic NPC is not only associated with a poor prognosis but also with short survival. Approval of penpulimab-kcqx by the FDA will increase the number of NPC patients who can benefit from its treatment.

Nasopharyngeal carcinoma is a virulent form of squamous cell carcinoma of nasopharyngeal epithelial tissue. It is distinct from other types of head and neck cancers due to its unique epidemiology, pathology, and strong association with the Epstein-Barr virus (EBV). Penpulimab-kcqx is a PD-1 inhibitor antibody that functions to inhibit NPC tumor growth by binding to PD-1 and preventing its engagement with PD-L1 and PD-L2.

Penpulimab has earlier been approved in China for multiple indications, including as a first-line treatment along with chemotherapy for locally advanced or metastatic squamous non-small cell lung cancer, third-line treatment of relapsed or refractory classical Hodgkin’s lymphoma, and third-line treatment of recurrent or metastatic NPC.

Penpulimab: A Novel Approach

Penpulimab, also referred to as AK105, is a human IgG1 monoclonal antibody targeting PD-1. It features a distinct Fc region mutation that eliminates interactions with Fc gamma receptors (FcƴRs) and the complement component C1 system, effectively preventing antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). These functions are typically triggered by binding to FcγR-IIIa, FcγR-Ia, and C1q, respectively. Moreover, the IgG1 backbone provides structural stability, helping to reduce immune escape.

Clinical trials and approval

The approval of penpulimab-kcqx as a first-line treatment was based on the randomized, double-blind AK105-304 trial (ClinicalTrials.gov Identifier: NCT04974398), and the approval of penpulimab-kcqx as a single agent for NPC was based on the open-label, single-arm AK105-202 study (ClinicalTrials.gov Identifier: NCT03866967).

The AK105-304 trial was a Phase III, multi-center, randomized, double-blind, placebo-controlled study designed to assess the efficacy of Penpulimab (AK105) in combination with chemotherapy as a first-line treatment for non-keratinizing nasopharyngeal carcinoma (NPC). A total of 291 patients with histologically confirmed NPC who had not received prior systemic therapy for metastatic disease were enrolled and randomized in a 1:1 ratio to receive Penpulimab plus chemotherapy or placebo plus chemotherapy.

The chemotherapy regimen consisted of cisplatin (80 mg/m²) and gemcitabine (1,000 mg/m²), administered every three weeks for up to six cycles. Patients in the experimental arm received Penpulimab (200 mg IV) every two weeks, followed by Penpulimab monotherapy as maintenance. In the control arm, patients were allowed to switch to Penpulimab monotherapy upon disease progression.

Penpulimab demonstrated a 55% reduction in the risk of disease progression or death. The median progression-free survival (PFS) was 9.6 months in the Penpulimab group compared to 7.0 months in the placebo group. At the 12-month mark, 31% of patients in the Penpulimab arm remained progression-free, versus only 11% in the placebo arm.

The AK105-202 trial was a Phase II, open-label, single-arm study involving 125 patients with metastatic or unresectable non-keratinizing nasopharyngeal carcinoma (NPC) who had experienced disease progression following platinum-based chemotherapy and at least one additional prior line of therapy. Participants received penpulimab-kcqx monotherapy for up to 24 months, or until disease progression or unacceptable toxicity occurred.

The primary endpoints objective response rate (ORR) and duration of response (DOR) were assessed by an independent radiology review committee based on RECIST v1.1 criteria. The results showed a partial response in 27% of patients, with an ORR of 28% the median DOR was not reached and 46% of responders maintained a DOR of at least 12 months.

Safety profile

Penpulimab, when used in combination with cisplatin, carboplatin, and gemcitabine, was most commonly associated with adverse events such as vomiting, nausea, hypothyroidism, constipation, decreased appetite, weight loss, cough, COVID-19, infections, fatigue, rash, and fever, each reported in at least 20% of patients.

For patients treated with penpulimab as a single agent, the most frequently observed adverse events, affecting at least 20% of individuals, were musculoskeletal pain and hypothyroidism.

Serious and potentially fatal adverse drug reactions, including pneumonitis, colitis, septic shock, and hepatitis, were reported in approximately 1% of cases. Immune-mediated toxicities, particularly pneumonitis and colitis, require careful monitoring.

Overall, penpulimab exhibited a manageable safety profile, with the majority of adverse events classified as mild to moderate in severity.

Impact and Future Viewpoint

This FDA approval provides a new immunotherapy option for patients with advanced NPC, potentially improving outcomes and offering hope for those with limited treatment alternatives. The approval also emphasizes the importance of continuing research and development in rare cancers, aiming to enhance patient care and survival rates.

Future research will explore long-term benefits, optimal uses, and potential drug combinations, including targeted agents or radiation therapy. Its global approval will increase patient access to this promising immunotherapy, offering new hope for NPC treatment.

References

Akeso Announces FDA Approval for Penpulimab-kcqx in Two BLA Indications for Comprehensive Treatment of Advanced Nasopharyngeal Carcinoma, 25 April 2025, Akesobio, https://www.akesobio.com/en/media/akeso-news/250425/

FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma, US Food and Drug Administration, 24 April 2025 https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-penpulimab-kcqx-non-keratinizing-nasopharyngeal-carcinoma

Chen X, Wang W, Zou Q, et al, Penpulimab, an anti-PD-1 antibody, for heavily pretreated metastatic nasopharyngeal carcinoma: a single-arm phase II study. Signal Transduct Target Ther. 2024 Jun 19;9(1):148. Doi: 10.1038/s41392-024-01865-6. PMID: 38890298; PMCID: PMC11189389.

Song Y, Zhou K, Jin C, et al, Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201). Front Oncol. 2022 Jul 7;12:925236. doi: 10.3389/fonc.2022.925236. PMID: 35875118; PMCID: PMC9301139. https://pmc.ncbi.nlm.nih.gov/articles/PMC9301139/

Akeso announces FDA approval for penpulimab-kcqx in two BLA indications for comprehensive treatment of advanced nasopharyngeal carcinoma. News release. Akeso. April 24, 2025. https://www.prnewswire.com/news-releases/akeso-announces-fda-approval-for-penpulimab-kcqx-in-two-bla-indications-for-comprehensive-treatment-of-advanced-nasopharyngeal-carcinoma-302437965.html.

Chaosu Hu, Xiaozhong Chen, Tingting Xu, et al, Penpulimab versus placebo in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A global, multicenter, randomized, double-blind, phase 3 trial (AK105-304) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT011.

The article is extensively reviewed and fact-checked by the editorial team of pharmacally.com

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FDA Approves Zevaskyn (Prademagene Zamikeracel) for Recessive Dystrophic Epidermolysis Bullosa (RDEB): Gene Therapy Targets COL7A1 Gene and Boosts Type VII Collagen (C7)

May 17, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Written by: Rikesh Dighore (M Pharm., Pharmacology) , and Soniya Hajare (M Pharm.., Pharmacology)

For the treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB), the FDA has approved Zevaskyn (prademagene zamikeracel), the first autologous cell-based gene therapy. The treatment of RDEB, a rare and disabling genetic skin condition marked by fragile skin, prone to blistering and recurrent wounds, has advanced significantly with this approval. Abeona Therapeutics has developed Zevaskyn, a novel cell-based gene therapy scientifically known as prademagene zamikeracel (previously referred to as pz-cel or EB-101). By directly addressing the genetic mutation responsible for the disease, it represents a significant advancement in the treatment of RDEB. By using genetically modifying skin cells to create type VII collagen, Zevaskyn provides a novel therapeutic approach that improves wound healing and quality of patient’s life.

About Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is one of the subtypes of various Epidermolysis Bullosa. Epidermolysis Bullosa is the heterogeneous group of inherited mechanobullous disorders triggered by mutations in genes that encode structural proteins in the skin. RDEB involves mutations in the COL7A1 gene, which codes for type VII collagen (C7). Type II collagen protein is essential to the skin’s structural integrity. The mutation in this gene leads to anomalous synthesis of type II collagen or faulty compilation of the protein into anchoring fibrils, which results in poor epidermal-dermal cohesion.

As a result skin is become very delicate because the layers do not attach correctly without this protein. Hence, even with little contact or impact, people with RDEB experiences open wounds and persistent blistering. A complication which arises due to this condition includes severe infections, malnourishment, scarring, joint contractures, and an elevated risk of aggressive squamous cell carcinoma (SCC). The disease affects both the skin and internal mucous membranes. Many patients have a shorter life expectancy and frequently do not live past their 30s or 40s.

However, there is currently no cure for RDEB. Symptomatic treatment which includes pain management, infection prevention and control, and careful wound care, has been the main focus of standard care. Despite being necessary, these supportive treatments are quite strenuous, necessitate intensive daily interventions, and fail to address the underlying genetic problem. Additionally, current topical treatments like Vyjuvek which was approved for Dystrophic Epidermolysis Bullosa are insufficient for large, chronic, or deep wounds that considerably lower quality of life and raise the risk of death, even though they work well for minor, superficial wounds.

Hence, a targeted, long-lasting treatment alternative was in urgent need as evident from the significant morbidity and mortality rates linked to RDEB.

Zevaskyn (prademagene zamikeracel): A Novel Approach

Zevaskyn (prademagene zamikeracel) received FDA approval in April 2025, tackled a critical gap in treatment. This autologous, ex vivo gene therapy uses a retroviral vector to modify a patient’s own keratinocytes, allowing them to produce functional type VII collagen. The corrected cells are then grafted onto the patient’s chronic wounds. Unlike topical treatments that require ongoing application, Zevaskyn is designed as a one-time therapy offering long-lasting effects by providing permanent structural repair to the skin.

By enhancing skin integrity, reducing infection rates, and maybe slowing the growth of skin malignancies, this therapeutic breakthrough not only lessens the burden of care and discomfort, but also has the potential to extend life. Zevaskyn thus fills a long standing medical gap in the treatment of RDEB and marks a significant breakthrough.

Clinical Trials and FDA Approval

The FDA approval of ZEVASKYN (prademagene zamikeracel) was primarily based on the pivotal Phase 3 VIITAL™ study (NCT04227106). This multicenter, randomized, intrapatient-controlled trial evaluated the efficacy of a single application of ZEVASKYN in treating large, chronic wounds in patients with recessive dystrophic epidermolysis bullosa (RDEB). Patients with RDEB received skin grafts made of their own genetically modified cells as part of this randomized, controlled study. The study met its two co-primary endpoints.

Wound Healing: 81% of wounds treated with ZEVASKYN achieved 50% or more healing at six months, compared to 16% in control wounds treated with standard care (P<0.0001).

Pain Reduction: Patients reported significant pain reduction from baseline, as assessed by the Wong-Baker FACES scale.

Additionally, the FDA considered data from a Phase 1/2a study (NCT01263379), demonstrating long-term improvement in treated sites over a median follow-up of 6.9 years. These studies collectively supported the approval of ZEVASKYN for treating wounds in adult and pediatric patients with RDEB.

Rowan is a 3-year-old girl living with Recessive Dystrophic Epidermolysis Bullosa in her daily life.

Source: EB Research Partnership (YouTube) _ Rowan’s Story

Safety Profile

In clinical trials, Zevaskyn has shown a good safety profile. Localized to the treatment site, the most often reported side effects included itching and soreness during the grafting process. Significantly, the trials showed no significant side effects that were directly linked to the treatment.

The risk of immunological rejection and other issues related to allogeneic transplants is decreased when the patient’s own cells are used in the treatment.

Impact

Zevaskyn’s approval gives patients with RDEB new hope and marks a major advancement in the field of gene therapy. Zevaskyn has the potential to change the standard of care and enhance the lives of those badly affected by this debilitating illness by offering a medication that targets the underlying cause of the illness and not just symptoms.

Additionally, Zevaskyn enhances current treatments like Vyjuvek (beremagene geperpavec), a topical gene therapy that was authorized in 2023 to treat minor wounds in people with DEB. The dual-action armament in treatments like Vyjuvek, treating smaller lesions, and Zevaskyn, targeting larger, chronic wounds, enables a more thorough approach to disease management.

Conclusion

Zevaskyn’s FDA clearance represents a major advancement in the management of recessive dystrophic epidermolysis bullosa a rare and devastating genetic skin disorder that has long imposed a severe burden on patients and families. ZEVASKYN, the first approved topical gene therapy for this condition, offers new hope by directly addressing the underlying genetic defect.

Its approval was backed by compelling data from the pivotal Phase 3 VIITAL™ trial, which showed significant improvements in wound healing and pain reduction two of the most debilitating aspects of RDEB. Unlike traditional therapies focused only on symptom management, ZEVASKYN delivers a corrected COL7A1 gene to the skin, promoting true biological repair.

Zevaskyn may open the door to more personalized and efficient treatments for uncommon genetic illnesses as research advances and availability increases.

References

Zevaskyn approval letter, US Food and Drug Administration, available from https://www.fda.gov/media/186513/download?attachment

Bischof J, Hierl M, Koller U. Emerging Gene Therapeutics for Epidermolysis Bullosa under Development. Int J Mol Sci. 2024 Feb 13;25(4):2243. doi: 10.3390/ijms25042243. PMID: 38396920; PMCID: PMC10889532.

Luis Soro, Do, Cynthia Bartus, Stephen Purcell et al, Recessive Dystrophic Epidermolysis Bullosa A Review of Disease Pathogenesis and Update on Future Therapies, May 2015, Volume 8, Number 5, The Journal of Clinical and Aesthetic Dermatology. https://pmc.ncbi.nlm.nih.gov/articles/PMC4445895/pdf/jcad_8_5_41.pdf

Hon KL, Chu S, Leung AKC. Epidermolysis Bullosa: Pediatric Perspectives. Curr Pediatr Rev. 2022; 18(3):182-190. Doi: 10.2174/1573396317666210525161252. PMID: 34036913.

Gurevich I, Agarwal P, Zhang P, Dolorito JA, Oliver S, Liu H, Reitze N, Sarma N, Bagci IS, Sridhar K, Kakarla V, Yenamandra VK, O’Malley M, Prisco M, Tufa SF, Keene DR, South AP, Krishnan SM, Marinkovich MP. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022 Apr;28(4):780-788. Doi: 10.1038/s41591-022-01737-y. Epub 2022 Mar 28. PMID: 35347281; PMCID: PMC9018416.

Abeona Therapeutics (2025). Zevaskyn (prademagene zamikeracel): Product Information and VIITAL Study Results. https://www.abeonatherapeutics.com

Koutsoukos SA, Bilousova G. Highlights of Gene and Cell Therapy for Epidermolysis Bullosa and Ichthyosis. Dermatol Ther (Heidelb). 2024 Sep;14(9):2379-2392. Doi: 10.1007/s13555-024-01239-4. Epub 2024 Aug 7. PMID: 39112824; PMCID: PMC11393223.

Phase 3, Open-label Clinical Trial of EB-101 for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB), ClinicalTrials.gov ID NCT04227106, https://clinicaltrials.gov/study/NCT04227106

The article is extensively reviewed and fact-checked by the editorial team of pharmacally.com

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FDA Grants Accelerated Approval to Avmapki Fakzynja Co-Pack for KRAS-Mutated Low Grade Serous Ovarian Cancer (LGSOC) Targeting RAS/MAPK Pathway

May 16, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Written By: Shital Gaikwad (M.Pharm Pharmacology) and Shital Doifode (M.Pharm Pharmacology)

In a significant progress in ovarian cancer treatment, the U.S. Food and Drug Administration (FDA) has granted accelerated approval to Avmapki Fakzynja Co-Pack (avutometinib capsules and defactinib tablets) for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. This approval represents the first and only FDA-approved treatment specifically for this rare subtype of ovarian cancer, marking a significant step forward in the fight against RAS/MAPK pathway-driven tumors. The approval is granted to Verastem Oncology, a biopharmaceutical company dedicated in the advancement of new treatments for patients with RAS/MAPK pathway-determined cancers. The FDA confirmed that this approval is under the accelerated approval, dependent on tumor response rate and duration of response; however, continuous approval for this indication will be subject to the results of the confirmatory trial. The FDA has also granted this combination Orphan Drug Designation.

Background and Need for New Treatments

Low-grade serous ovarian cancer (LGSOC) is a rare and recurrent form of epithelial ovarian cancer that mainly affects younger women and has a poor response to conventional chemotherapy. Approximately 30%–60% of LGSOC tumors carry KRAS mutations, activating the RAS/MAPK pathway and promoting uncontrolled tumor growth. KRAS mutation leads to continuous activation of the RAS/MAPK pathway.

There has been no FDA-approved treatment particularly targeting KRAS-mutated recurrent LGSOC, and patients have had limited treatment options like surgery, chemotherapy hormonal However each treatment options had certain limitations like low sensitivity to chemotherapy, high recurrence rate, toxicity of hormonal therapy and lacking of options of personalising treatment. This need highlighted the urgent demand for a targeted, effective, and tolerable treatment for this patient population.

Avmapki Fakzynja Co-Pack: A First-in-Class Combination

Avmapki Fakzynja Co-Pack is a novel oral combination therapy that includes:

Avutometinib: Avutometinib is an inhibitor of MEK1 that promotes the formation of inactive RAF/MEK complexes, thereby blocking RAF-mediated phosphorylation of MEK1/2. RAF and MEK are key components in the RAS/RAF/MEK/ERK (MAPK) signaling pathway. Avutometinib suppresses phosphorylation of MEK1/2 and ERK1/2, as well as the growth of tumor cell lines with KRAS mutations. Additionally, avutometinib treatment leads to an increase in phosphorylated focal adhesion kinase (FAK) levels in cancer cells.

Defactinib: Defactinib is a selective inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), both part of the FAK family of non-receptor tyrosine kinases. It has been shown to block FAK autophosphorylation in cancer cells in vitro and in mouse xenograft models.

This synergistic effect of both drugs leads to enhanced tumor response by concurrently inhibiting both tumor cell proliferation and survival mechanisms, making it a breakthrough option for KRAS-mutant LGSOC.

Clinical Trials and FDA Approval Basis

The accelerated approval of Avmapki Fakzynja Co-Pack was based on the results of the Phase II RAMP 201 clinical trial, which evaluated the safety and efficacy of avutometinib, a RAF/MEK inhibitor, alone and in combination with defactinib, a FAK inhibitor, in patients with recurrent low-grade serous ovarian cancer (LGSOC), particularly those with KRAS mutations.

Study Design

RAMP 201 (NCT04625270) was a multicenter, randomized, open-label Phase II study. It enrolled patients aged 18 years or older with histologically confirmed LGSOC or peritoneal cancer, measurable disease per RECIST 1.1 criteria, and disease progression or recurrence following at least one prior systemic therapy in the metastatic setting. The trial included patients with both KRAS-mutated and wild-type tumors. The primary objective was to assess the overall response rate (ORR) of the treatments.

Key findings from the trial:

Efficacy: In patients receiving the combination of avutometinib (3.2 mg twice weekly) and defactinib (200 mg twice daily), the confirmed ORR was 31%, with a complete response rate of 2% and a partial response rate of 29%. Among patients with KRAS-mutated tumors, the ORR was higher at 44%, compared to 17% in those with KRAS wild-type tumors.

Progression-Free Survival (PFS): The median PFS for the combination therapy was reported as 12.9 months, with longer durations observed in patients carrying KRAS mutations.

Confirmatory Trials

The continuous approval of this combination therapy is reliant on confirmatory evidence from the ongoing Phase III RAMP 301 trial, which will further evaluate clinical benefit in a broader population, including patients with and without KRAS mutations.

If the clinical benefit is confirmed, this would harden the combination as the standard of care for this difficult-to-treat cancer.

Side effects

Common (≥25%) Adverse Reactions (including lab abnormalities):

Elevated creatine phosphokinase, nausea, fatigue, increased AST and ALT, rash, diarrhea, musculoskeletal pain, edema, low hemoglobin, high bilirubin and triglycerides, low lymphocytes, abdominal pain, dyspepsia, acneiform dermatitis, vitreoretinal disorders, high alkaline phosphatase, stomatitis, itching, visual impairment, low platelets, constipation, dry skin, shortness of breath, cough, urinary tract infection, and low neutrophils.

Impact

The accelerated approval of Avmapki Fakzynja marks an important step in personalized oncology, especially for women fighting recurrent LGSOC with KRAS mutations, in view of few effective conventional treatment options.

This is the first FDA-approved therapy targeting KRAS-mutated LGSOC, reflecting a significant advancement in precision medicine. It also validates the potential of combining MEK and FAK inhibition to address tumor growth and resistance mechanisms.

Expert Opinion from Investigators

Dr. Rachel Grisham of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, and lead investigator of the RAMP 301 study, stated:

“This approval marks a much-needed therapeutic option and establishes this combination as the new standard of care for women with recurrent LGSOC harbouring a KRAS mutation.”

Prof. Susana Banerjee of The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, National Cancer Research Institute (NCRI), London also noted:

“To see this combination advance from early trials to become the first-ever FDA-approved therapy for LGSOC is inspiring and opens a new chapter in treating RAS/MAPK-pathway-driven cancers.”

Conclusion

The FDA’s accelerated approval of Avmapki Fakzynja Co-Pack introduces a much-needed targeted therapy for patients with KRAS-mutated recurrent low-grade serous ovarian cancer. With its novel dual-mechanism approach and promising clinical results, this combination therapy offers new hope for improving survival and quality of life in a population with limited options for LGSOC. However, its continuous approval and use depend on the success of the ongoing phase III trial. As precision oncology advances, the success of treatments like Avmapki underscores the importance of genetic profiling and personalized treatment strategies in overcoming rare and resistant cancers.

References

U.S. Food and Drug Administration. (2025, May 8). FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-combination-avutometinib-and-defactinib-kras-mutated-recurrent-low

Verastem Oncology. (2025, May 8). Verastem Oncology announces FDA approval of Avmapki Fakzynja Co-Pack for the treatment of KRAS-mutated recurrent low-grade serous ovarian cancer [Press release]. https://verastem.com/news/fda-approval-avmapki-fakzynja

ClinicalTrials.gov. (n.d.). A study of avutometinib (VS-6766) and defactinib in patients with recurrent low grade serous ovarian cancer (RAMP 201) (NCT04625270). National Library of Medicine. https://clinicaltrials.gov/study/NCT04625270

National Cancer Institute. (2024). Low-grade serous carcinoma of the ovary. https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-gynecologic-tumors/low-grade-serous-carcinoma

Highlights of Prescribing Information, Avmapkitm Fakzynjatm Co-Pack, available from https://www.verastem.com/pdf/avmapki-fakzynja-co-pack-full-prescribing-information.pdf

FDA Grants Accelerated Approval to Avmapki Fakzynja Co-Pack, Drugs.com,available from https://www.drugs.com/newdrugs/fda-grants-accelerated-approval-avmapki-fakzynja-co-pack-avutometinib-capsules-defactinib-kras-6516.html

Susana N. Banerjee et al. ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of VS-6766 (RAF/MEK clamp) alone and in combination with defactinib (FAK inhibitor) in recurrent low-grade serous ovarian cancer (LGSOC).. JCO 40, TPS5615-TPS5615(2022). DOI:10.1200/JCO.2022.40.16_suppl.TPS5615

The article is extensively reviewed and fact-checked by the editorial team of the pharmacally.com

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Japan First-in-the-World to approve Elevidys (Delandistrogene Moxeparvovec), one-of-the Costliest Gene Therapy Drug for Duchenne Muscular Dystrophy (DMD) in Children less than 4 years of age

May 15, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Written By: Pragati Ekamalli (B.Pharm)

Reviewed By: Vikas Londhe M.Pharm (Pharmacology)

In a groundbreaking step forward for genetic medicine, Japan has become the first country in the world to approve the use of Elevidys (delandistrogene moxeparvovec), a gene therapy created by Sarepta Therapeutics, for children under 4 years old diagnosed with Duchenne muscular dystrophy (DMD). DMD is a rare and life-threatening genetic disorder that leads to the progressive weakening and loss of muscle function, typically appearing in early childhood and worsening over time. Elevidys works by delivering a modified gene to help produce a version of the dystrophin protein, which is missing or defective in children with DMD. This approval represents a major milestone in the global effort to treat genetic disorders and could bring new hope to families affected by DMD. It also highlights Japan’s leadership in adopting cutting-edge medical treatments that may slow disease progression and improve quality of life for young patients.

Understanding Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a rare, inherited disorder that mainly affects boys due to its X-linked pattern of inheritance, meaning the faulty gene is carried on the X chromosome. The condition results from mutations in the DMD gene, which is responsible for producing dystrophin a protein critical for maintaining the strength and stability of muscle fibers. In the absence of functional dystrophin, muscles are unable to protect themselves from everyday stress, leading to ongoing damage, muscle fibres breakdown, and replacement by fat and scar tissue. Symptoms usually begin in early childhood, often with difficulty walking, running, or climbing stairs. As the disease progresses, most affected children lose their ability to walk by the age of 12 to 14. In later stages, DMD can lead to serious complications involving the heart and lungs, often reducing life expectancy into the twenties or thirties without advanced medical care.

Understanding Dystrophin Protein

Dystrophin is large structural protein (427kDa) present in cytoplasmic face of the sarcolemma. Dystrophin protein plays a crucial role in maintaining the integrity and function of muscle cells including skeletal muscle and cardiac muscle.

Dystrophin is act like an anchor which link internal cytoskeleton of a muscle fibre to the surrounding extracellular matrix by dystrophin-glycoprotein complex. This complex stabilizes muscle fibre during contraction. Dystrophin protein is coded with DMD gene on X-Chromosome and it is one of the largest human genes. Any mutation or deletion of DMD genes affects the dystrophin protein production, either less or completely diminished.

Elevidys: A Novel Gene Therapy Approach

Elevidys is an innovative gene therapy that uses an adeno-associated virus (AAV) as a delivery system to transport genetic material into the body. Specifically designed for Duchenne muscular dystrophy (DMD), Elevidys delivers a shortened but functional version of the dystrophin gene, called micro-dystrophin, directly into muscle cells. Although smaller than the full-length gene, micro-dystrophin includes the critical domains needed for the protein to support muscle fibre structure and function. By enabling cells to produce this essential protein, Elevidys targets the root cause of DMD — the absence of functional dystrophin. Administered as a single intravenous infusion, this therapy offers the promise of a one-time treatment that may slow disease progression and improve muscle strength, potentially transforming the standard of care for children living with DMD.

Japan’s Regulatory Approval

On August 14, 2024, Chugai Pharmaceutical Co., Ltd., a member of the Roche Group, submitted a regulatory application to Japan’s Ministry of Health, Labour and Welfare (MHLW) seeking approval for Elevidys, a gene therapy for Duchenne muscular dystrophy (DMD). The application specifically targeted ambulatory boys aged 3 to 7 years who do not have deletions in exons 8 and/or 9 of the DMD gene and who are not immune to the AAVrh74 viral vector used to deliver the treatment. This submission was supported by data from the global Phase III EMBARK study, which evaluated the safety and effectiveness of Elevidys. The trial did not meet its primary endpoint improving motor function as measured by the North Star Ambulatory Assessment (NSAA), however clinically meaningful benefits were observed in key secondary outcomes, including faster time to rise from the floor and improved 10-meter walk speed. Despite the mixed results, Japan’s MHLW granted priority review to the application and ultimately approved Elevidys for use in children less than 4 years of age. With this decision, Japan became the first country to authorize Elevidys for this younger age group, reflecting its proactive approach to approving innovative therapies for rare and serious diseases like DMD. This landmark approval offers new hope for patients and families affected by this devastating condition.

Global Context

Before Japan’s historic approval, the U.S. Food and Drug Administration (FDA) granted Elevidys accelerated approval in June 2023 for ambulatory children aged 4 through 5 years with Duchenne muscular dystrophy (DMD). The FDA’s decision was based on evidence that the therapy successfully prompted the production of micro-dystrophin, the shortened version of the dystrophin protein essential for muscle health. However, this approval was conditional, with continued authorization depending on the confirmation of meaningful clinical benefits in ongoing follow-up trials. Japan’s more inclusive approval for children under 4 years old not only marks a significant expansion of access to this gene therapy but also sets a global precedent. It signals to other regulatory agencies the potential value of early intervention in DMD. As new clinical data emerges and confirmatory studies continue, more countries may follow suit, potentially reshaping the global treatment landscape for this devastating disease and offering hope for earlier and more effective management of DMD in young patients.

Conclusion

The approval of Elevidys in Japan for children younger than 4 years of age marks a major breakthrough in the treatment of Duchenne muscular dystrophy (DMD). Unlike traditional therapies that mainly manage symptoms, Elevidys directly targets the genetic root of the disease by introducing a functional version of the dystrophin gene. This approach offers the potential not just to slow the progression of muscle degeneration, but to meaningfully alter the course of the disease, particularly when administered early in life. The decision by Japan’s health authorities highlights the critical role of early intervention and paves the way for improving long-term outcomes for children affected by DMD. Moreover, this milestone emphasizes the value of ongoing scientific research, clinical trials, and international collaboration in developing transformative therapies for rare and life-threatening conditions.

References

1. Sarepta Therapeutics Announces Approval in Japan of ELEVIDYS, a Gene Therapy to Treat Duchenne Muscular Dystrophy, 13 May 2025, Sarepta Therapeutics https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-approval-japan-elevidys-gene

2. A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD) (EMBARK), NCT05096221, ClinicalTrials.gov, available from https://clinicaltrials.gov/study/NCT05096221

3. Roche announces new results from EMBARK demonstrating significant sustained benefits of Elevidys in ambulatory individuals with Duchenne muscular dystrophy (DMD), 27 January 2025, https://www.roche.com/media/releases/med-cor-2025-01-27

4. Gao QQ, McNally EM. The Dystrophin Complex: Structure, Function, and Implications for Therapy. Compr Physiol. 2015 Jul 1; 5(3):1223-39. Doi: 10.1002/cphy.c140048. PMID: 26140716; PMCID: PMC4767260.

5. Venugopal V, Pavlakis S. Duchenne Muscular Dystrophy. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482346/

6. Chugai Receives Regulatory Approval for “ELEVIDYS” as a Gene Therapy Product for Duchenne Muscular Dystrophy in Japan, 13 May 2025, Chugai Pharmaceuticals,https://www.chugaipharm.co.jp/english/news/detail/20250513181500_1160.html

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Roche Secures FDA Breakthrough Device Designation for AI-Powered VENTANA TROP2 Diagnostic in Non-Small Cell Lung Cancer

May 4, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Medically Written and Reviewed By Pavan Reddy (Biomedical Engineer)

Introduction: Roche’s New AI Tool

In an exciting step forward for cancer diagnosis, the U.S. Food and Drug Administration (FDA) have given Breakthrough Device Designation to a new tool developed by Roche. The tool is called the VENTANA TROP2 assay, and it uses artificial intelligence (AI) to detect and treatment stratification of lung cancer known as non-small cell lung cancer (NSCLC).

NSCLC is the most common form of lung cancer, making up about 85% of all lung cancer cases around the world. Roche’s test doesn’t just find cancer. It also helps to figure out the best treatment options for each patient by analyzing how the cancer behaves. This new AI-driven approach could lead to faster, more accurate diagnoses, and more personalized treatment plans, giving patients a better chance of successful treatment.

What Is TROP2 and Why Does It Matter?

TROP2 is a special kind of protein found on the surface of certain cells, including many cancer cells. It’s especially common in epithelial cancers, like non-small cell lung cancer (NSCLC). When a tumor has high levels of TROP2, it usually means the cancer is growing quickly and may lead to a poorer outcome for the patient. Because of this, TROP2 is considered an important biomarker a signal can use to better understand the cancer and choose the right treatment.

Unlike older companion diagnostic tests that only look at protein levels on the surface of cancer cells Roche’s VENTANA TROP2 assay uses artificial intelligence (AI) to measure exactly how much TROP2 is also present inside a tumor sample. This helps oncologists get very precise information about the cancer, which can guide them in choosing more targeted, effective therapies for each patient.

How the AI Tool Works: Powered by Digital Pathology

Roche’s VENTANA TROP2 (EPR20043) RxDx device is an immunohistochemistry (IHC) assay is part of a larger digital system called uPath, which is the company’s digital pathology platform. This platform is designed to look at complex tissue samples more easily and accurately.

By using advanced AI algorithms based image analysis with a level of diagnostic precision; uPath can analyze cancer cells more quickly and consistently than traditional methods. It reduces the chance of human error and helps ensure that results are reliable and repeatable. This means pathologists can make faster, more confident decisions about a patient’s diagnosis.

Implications for Personalized Medicine

The FDA’s Breakthrough Device Designation highlights the significant potential of Roche’s VENTANA TROP2 assay to enhance clinical outcomes for patients. This designation recognizes the assay’s ability to support more personalized and targeted treatment strategies, particularly for individuals with TROP2-positive cancers.

By accurately identifying patients who are most likely to respond to TROP2-targeted therapies, the assay enables oncologists to select the most effective treatment options from the outset. This can lead to higher response rates, improved survival outcomes, and a more efficient use of therapies in clinical practice.

Looking Ahead: Shaping the Future of Lung Cancer Diagnosis

As the VENTANA TROP2 assay continues through clinical validation and regulatory review, it shows strong potential to transform how non-small cell lung cancer (NSCLC) is diagnosed and treated. By offering more precise insights into tumor biology, the assay could become a powerful tool in guiding personalized cancer care.

This advancement also reinforces the growing importance of precision medicine an approach that tailors treatment to each patient’s unique disease profile. If successful, this assay could help set a new standard in how lung cancer is diagnosed and managed, leading to better outcomes for patients.

Reference

1. Roche granted FDA Breakthrough Device Designation for first AI-driven companion diagnostic for non-small cell lung cancer, 29 April 2025, Roche Diagnostic

2. Mito R, et al. Clinical impact of TROP2 in non‐small lung cancers and its correlation with abnormal p53 nuclear accumulation.Pathol Int. 2020;70(5):287-294.

3. Shvartsur A, et al. Trop2 and it’s over expression in cancers: regulation and clinical/therapeutic implications. Genes & Cancer. 2015 Mar; 6(3-4): 84-105.

4. Roche receives FDA breakthrough label for AI-powered lung cancer companion diagnostic test, 29 April 2025, fierce biotech, available from https://www.fiercebiotech.com/medtech/roche-receives-fda-breakthrough-label-ai-powered-lung-cancer-companion-diagnostic-test

FDA expand drug label of ALK’s Odactra for the Treatment of House Dust Mite Allergy in Young Children

April 23, 2025

by official.ajinkya11@gmail.com with No Comment Disease & Drugs New Drug Approval

Written By Lavanya Chavhan B.Pharm

Reviewed and Fact Checked by Vikas Londhe, M.Pharm (Pharmacology)

The U.S. Food and Drug Administration (FDA) has recently expanded label for ALK-Abelló’s Odactra, a sublingual immunotherapy tablet, to treat house dust mite (HDM) allergies in children as young as five years old. This landmark decision expands access to a groundbreaking therapy previously approved for adults, offering a safe and convenient option for young children grappling with this pervasive allergen.

What is Odactra?

Odactra s the allergen extract of House Dust Mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus). It is prescription medication designed to address house dust mite (HDM)-induced allergic rhinitis, with or without conjunctivitis. It is indicated in case of Confirmed positive in vitro testing for IgE antibodies to Dermatophagoides farinae or Dermatophagoides pteronyssinus house dust mites. It is approved in the population from 5 years old to 65 years old age patient.

Administered as a once-daily tablet as sublingual that dissolves under the tongue, it works by exposing the immune system to small, controlled amounts of dust mite allergens. Over time, this exposure helps desensitize the body, reducing the severity of allergic reactions. Unlike traditional treatments such as antihistamines or nasal corticosteroids, which only alleviate symptoms, Odactra targets the root cause of allergies, offering potential long-term relief.

Significance of the Approval

House dust mites (HDMs) are microscopic arachnids (related to ticks and spiders) that thrive in warm, humid environments. They feed on dead human skin cells and are commonly found in mattresses, pillows, upholstered furniture, and carpets. The allergens are primarily from their faeces and body fragments. House dust mites are a leading trigger of perennial allergies, affecting millions of children worldwide.

For sensitized individuals, short-term exposure can cause immediate allergic reactions, including Allergic rhinitis, Asthma exacerbations, Allergic conjunctivitis, and Skin irritation. Prolonged exposure and chronic sensitization can lead to Persistent asthma, chronic rhino sinusitis, Atopic dermatitis, increased risk of developing new allergies.

Chronic symptoms like sneezing, nasal congestion, and itchy eyes can disrupt sleep, school performance, and overall quality of life. For young children, whose immune systems are still developing, uncontrolled allergies may also heighten the risk of developing asthma.

Global Prevalence of HDM allergy estimated to affect 65–130 million people globally, in some regions, up to 80% of asthmatic children are sensitized to HDM however in adults’ sensitization rates range from 20% to 30% in general populations.

A renowned pediatric allergist involved in Odactra’s clinical trials, emphasized the importance of this approval: “Immunotherapy at an early age can alter the course of allergic disease. Odactra’s sublingual form is particularly advantageous for children, avoiding the anxiety associated with allergy shots.”

Clinical Trial Insights

The clinical trial (NCT04145219) performed in children was double-blind, placebo-controlled, randomized field efficacy study conducted in Europe, the United States and Canada for a duration of approximately 12 months comparing the efficacy of ODACTRA (N=693) to placebo (N=706) in the treatment of HDM allergic rhinitis/rhino conjunctivitis with or without asthma in children 5 through 11 years of age.

The FDA’s decision followed this phase III study which evaluated safety and efficacy of odactra in young children. Results demonstrated a significant reduction in allergy symptoms and medication use compared to placebo. Participants also reported improved sleep and daily functioning. The trial highlighted Odactra’s tolerability, with most side effects being mild, such as oral itching or throat irritation. Severe reactions were rare, aligning with the therapy’s established safety profile in adults.

Safety and Accessibility

During the pediatric clinical trial, the most commonly reported adverse reactions included ear and mouth itching, followed by throat irritation, abdominal pain, altered taste, and lip swelling. However, since its initial approval, Odactra has carried a black box warning for anaphylaxis and is contraindicated in individuals with uncontrolled asthma.

Conclusion

The FDA’s expansion of Odactra’s approval marks a pivotal advancement in managing HDM allergies in children. By offering a convenient, home-based therapy, Odactra empowers families to address allergies proactively, potentially reducing long-term health burdens. Parents of affected children are encouraged to consult allergists to determine if Odactra is a suitable option.

As research continues to underscore the benefits of early intervention, Odactra stands out as a beacon of innovation in the quest to improve pediatric health outcomes.

References

Package Insert, Highlights of Prescribing Information, Odactra, ALK-Abelló A/S available from https://www.fda.gov/media/103380/download

2. Odactra, US Food and Drug Administration, 17 March 2025 available from https://www.fda.gov/vaccines-blood-biologics/allergenics/odactra

3. Bracken SJ, Adami AJ, Szczepanek SM, et al, Long-Term Exposure to House Dust Mite Leads to the Suppression of Allergic Airway Disease Despite Persistent Lung Inflammation. Int Arch Allergy Immunol. 2015;166(4):243-58. doi: 10.1159/000381058. Epub 2015 Apr 28. PMID: 25924733; PMCID: PMC4485530.

4. Dust Mites, American Lung Association, 05 Nov 2024, available from https://www.lung.org/clean-air/indoor-air/indoor-air-pollutants/dust-mites

5. Schuster, Antje et al., Efficacy and safety of SQ house dust mite sublingual immunotherapy-tablet (12 SQ-HDM) in children with allergic rhinitis/rhino conjunctivitis with or without asthma (MT-12): a randomised, double-blind, placebo-controlled, phase III trial, The Lancet Regional Health – Europe, Volume 48, 101136

6. Solarz, K., Obuchowicz, A., Asman, M. et al. Abundance of domestic mites in dwellings of children and adolescents with asthma in relation to environmental factors and allergy symptoms. Sci Rep 11, 18453 (2021). https://doi.org/10.1038/s41598-021-97936-7.

FDA Approves Qfitlia: First siRNA Therapy for Haemophilia Prophylaxis

April 23, 2025

by official.ajinkya11@gmail.com with No Comment Disease & Drugs New Drug Approval

Written by Aishwarya Shinde (B.Pharm)

Reviewed and Fact Checked by Vikas Londhe M.Pharm (Pharmacology)

The U.S. Food and Drug Administration (FDA) has granted approval for Qfitlia (fitusiran), a groundbreaking therapy designed for the routine prophylaxis of bleeding episodes in individuals with haemophilia A or B. This approval, announced on March 28, 2025, marks a significant advancement in the treatment of these rare genetic bleeding disorders. Qfitlia is authorized for use in adults and pediatric patients aged 12 years and older, regardless of the presence of factor VIII or IX inhibitors.

Haemophilia A and B

Haemophilia is a rare, inherited bleeding disorder caused by deficiencies in clotting factors, leading to prolonged bleeding episodes. The two main types are Haemophilia A (deficiency of Factor VIII) and Haemophilia B (deficiency of Factor IX), both inherited as X-linked recessive disorders. Since the defective gene is located on the X chromosome, males (XY) are typically affected, while females (XX) are usually carriers. However, rare cases of female haemophilia can occur due to lyonization, where the healthy X chromosome is inactivated.

Conventional treatments for haemophilia focus on managing bleeding episodes and preventing complications. Replacement therapy includes recombinant or plasma-derived Factor VIII concentrates for Haemophilia A and Factor IX concentrates for Haemophilia B. Prophylactic treatment involves regular infusions to prevent bleeding, particularly in severe cases. Additional therapies include Desmopressin (DDAVP) for mild Haemophilia A, which stimulates Factor VIII release, and antifibrinolytics like tranexamic acid to stabilize clots, especially in mucosal bleeding.

Recent advances in treatment include gene therapy, such as etranacogene dezaparvovec for Haemophilia B, offering potential long-term solutions. Haemophilia A is more prevalent, affecting approximately 1 in 5,000 male births, while Haemophilia B occurs in 1 in 30,000 male births. Globally, an estimated 400,000 people are affected by the disorder. Ongoing research and novel therapies aim to improve quality of life and reduce the burden of this chronic condition.

Need of an Advance Therapy

However the advanced therapies are needed for haemophilia A and B to address the limitations of conventional treatments and improve patient outcomes. While traditional factor replacement therapies are effective, they require frequent intravenous infusions, which can be burdensome for patients and may lead to complications like inhibitor development (antibodies against clotting factors). Additionally, some patients experience breakthrough bleeding despite prophylaxis, highlighting the need for more durable and convenient solutions.

Qfitlia: A Novel Approach to Haemophilia Management

Developed by Sanofi, Qfitlia (Fitusiran) is an RNA interference (RNAi) therapeutic developed for the treatment of haemophilia A and B, as well as other bleeding disorders. It is designed to reduce bleeding episodes by silencing the production of antithrombin (AT), a natural anticoagulant protein, through RNA interference rather than replacing the missing clotting factors (as in conventional therapies).

Fitusiran is a synthetic siRNA molecule encapsulated in a lipid nanoparticle for targeted delivery to hepatocytes (liver cells). Once inside the liver, it binds to the messenger RNA (mRNA) encoding antithrombin (SERPINC1 gene).

The siRNA triggers the degradation of antithrombin mRNA, reducing antithrombin production. Lower antithrombin levels shift the hemostatic balance toward a pro-coagulant state, promoting thrombin generation and improving clot formation.

In haemophilia, deficient Factor VIII (Haemophilia A) or Factor IX (Haemophilia B) leads to impaired thrombin burst, by reducing antithrombin, fitusiran bypasses the need for exogenous clotting factors, allowing even low levels of endogenous Factors VIII/IX to work more effectively.

The therapy is administered via subcutaneous injections as few as six times per year, offering a significant reduction in treatment burden compared to existing options. It is available in a convenient prefilled pen or vial-and-syringe format, making it easier for patients and caregivers to manage.

Clinical Efficacy

The FDA’s approval was based on data from Sanofi’s ATLAS clinical trial program, which included phase 3 studies such as ATLAS-A/B and ATLAS-INH.

ATLAS-A/B study was a Phase 3, multicenter, open-label, randomized trial evaluating the efficacy and safety of fitusiran prophylaxis in males aged 12 years and older with severe haemophilia A or B without inhibitors. The study enrolled 120 participants across 45 sites in 17 countries.Participants were randomized in a 2:1 ratio to receive either once-monthly 80 mg subcutaneous fitusiran prophylaxis or continue with on-demand clotting factor concentrates for duration of 9 months.

Key Findings includes, Annualized Bleeding Rate (ABR): The median ABR was 0.0 (interquartile range [IQR] 0.0–3.4) in the fitusiran group, compared to 21.8 (IQR 8.4-41.0) in the on-demand group. The estimated mean ABR was significantly lower in the fitusiran group (3.1) than in the on-demand group (31.0), representing an approximate 90% reduction. Bleed-Free Participants: Approximately 51% of participants in the fitusiran group experienced no treated bleeds during the study period, compared to 5% in the on-demand group.

ATLAS-INH study, was a Phase 3, open-label, randomized trial evaluating the efficacy and safety of fitusiran in individuals aged 12 years and older with severe haemophilia A or B who have inhibitors to factor VIII or IX. Participants were randomly assigned in a 2:1 ratio to receive once-monthly 80 mg subcutaneous fitusiran prophylaxis or to continue with on-demand treatment using bypassing agents (BPAs).

Fitusiran prophylaxis led to a significant reduction in the annualized bleeding rate (ABR), with a 90.8% decrease compared to the on-demand BPA group. Approximately 66% of participants receiving fitusiran experienced zero treated bleeds during the study period, compared to 5% in the BPA group.

Based on the results from the ATLAS-INH and other related trials, the U.S. Food and Drug Administration (FDA) approved fitusiran, marketed as Qfitlia, for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients aged 12 years and older with haemophilia A or B, with or without inhibitors.

Safety Profile

The safety profile of Qfitlia includes warning for serious thrombotic event and acute and recurrent gall bladder disease. The most common treatment-emergent adverse event in the fitusiran group was increased alanine aminotransferase levels, observed in 32% of participants.

Benefits for Patients

Qfitlia represents a paradigm shift in haemophilia care by combining effective bleed protection with infrequent dosing and simplified administration. “This approval highlights our commitment to advancing innovation and improving care for the rare blood disorders community,” said Brian Foard, executive vice president at Sanofi Tanya Wroblewski, MD, deputy director at the FDA’s Center for Drug Evaluation and Research, emphasized that this therapy “can be administered less frequently than other existing options,” improving quality of life for patients.

Conclusion

The FDA’s approval of Qfitlia marks a transformative moment for individuals living with haemophilia A or B. By offering effective bleed prevention with minimal treatment burden, this innovative therapy has the potential to significantly improve patient outcomes and redefine standards of care worldwide.

References

1. FDA Approves Novel Treatment for Haemophilia A or B, with or without Factor Inhibitors, US Food and Drug Administration, 28 March 2025, available form https://www.fda.gov/news-events/press-announcements/fda-approves-novel-treatment-Haemophilia-or-b-or-without-factor-inhibitors

2. Press Release: Qfitlia approved as the first therapy in the US to treat Haemophilia A or B with or without inhibitors, Sanofi, 28 March 2025, available from https://www.sanofi.com/en/media-room/press-releases/2025/2025-03-28-20-07-38-3051637

3. Castaman G, Matino D. Haemophilia A and B: molecular and clinical similarities and differences. Haematologica. 2019 Sep;104(9):1702-1709. doi: 10.3324/haematol.2019.221093. Epub 2019 Aug 8. PMID: 31399527; PMCID: PMC6717582.

4. Mannucci PM, Franchini M. Is haemophilia B less severe than haemophilia A? Haemophilia. 2013 Jul;19(4):499-502. Doi: 10.1111/hae.12133. Epub 2013 Mar 21. PMID: 23517072.

5. Meeks SL, Batsuli G. Haemophilia and inhibitors: current treatment options and potential new therapeutic approaches. Haematology Am Soc Hematol Educ Program. 2016 Dec 2; 2016(1):657-662. Doi: 10.1182/asheducation-2016.1.657. PMID: 27913543; PMCID: PMC6142469.

6. Treatment of Haemophilia, US Centre for disease control and prevention, 13 Nov 2024, available from https://www.cdc.gov/Haemophilia/treatment/index.html

7. Miesbach W, Schwäble J, Müller MM, Seifried E. Treatment Options in Haemophilia. Dtsch Arztebl Int. 2019 Nov 22; 116(47):791-798. Doi: 10.3238/arztebl.2019.0791. PMID: 31847949; PMCID: PMC6937545.

8. Von Drygalski A., Giermasz A., Castaman G., Key N.S., Lattimore S., Leebeek F.W.G., Miesbach W., Recht M., Long A., Gut R., et al. Etranacogene Dezaparvovec (AMT-061 Phase 2b): Normal/near Normal FIX Activity and Bleed Cessation in Haemophilia B. Blood Adv. 2019;3:3241–3247. Doi: 10.1182/bloodadvances.2019000811.

9. Mehta P, Reddivari AKR. Haemophilia. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551607/

10. Qfitlia (fitusiran) injection, Highlights Of Prescribing Information, Genzyme Corporation, A Sanofi Company, available from https://products.sanofi.us/qfitlia/qfitlia.pdf

11. Young G, Srivastava A, Kavakli K, et al, Rangarajan S. Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial. Lancet. 2023 Apr 29;401(10386):1427-1437. Doi: 10.1016/S0140-6736(23)00284-2. Epub 2023 Mar 29. PMID: 37003287.

12. Srivastava A, Rangarajan S, Kavakli K, et al, Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial. Lancet Haematol. 2023 May;10(5):e322-e332. Doi: 10.1016/S2352-3026(23)00037-6. Epub 2023 Mar 29. PMID: 37003278.

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FDA Grants Accelerated Approval to Avmapki Fakzynja Co-Pack for KRAS-Mutated Low Grade Serous Ovarian Cancer (LGSOC) Targeting RAS/MAPK Pathway

Japan First-in-the-World to approve Elevidys (Delandistrogene Moxeparvovec), one-of-the Costliest Gene Therapy Drug for Duchenne Muscular Dystrophy (DMD) in Children less than 4 years of age

Roche Secures FDA Breakthrough Device Designation for AI-Powered VENTANA TROP2 Diagnostic in Non-Small Cell Lung Cancer

FDA expand drug label of ALK’s Odactra for the Treatment of House Dust Mite Allergy in Young Children

FDA Approves Qfitlia: First siRNA Therapy for Haemophilia Prophylaxis

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