Yeztugo

“Gilead’s Yeztugo (Lenacapavir) Receives FDA Nod as First Twice-Yearly Injectable for HIV PrEP”

by with No Comment New Drug Approval

27 June 2025

Category: New Drug Approval I Sexual Health I

HIV & Infectious Diseases

Written By: Dewanshee Ingale BPharm

Reviewed By: Pharmacally Editorial Team

Glilead

In the landmark development, FDA has approved Yeztugo (lenacapavir), an antiretroviral drug representing a novel class of antiretroviral drug called capsid inhibitors, invented by the Gilead Sciences, which is approved as a first, and only biannual injection for pre-exposure prophylaxis (PrEP) to protect the human body from sexually acquired HIV in adults and adolescents especially those who are weighing 35 kg and more. The sanction is considered a historic innovation in HIV prevention, presenting a highly efficient and suitable option that addresses the adherence problems, treatment burden, and disease stigma. Authorities believe that Yeztugo has the potential to significantly enhance pre-exposure prophylaxis (PrEP) initiation and adherence, especially in populations facing difficulties with existing treatments. The invention of Yeztugo (lenacapavir) is a breakthrough to end the HIV epidemic.          

About Yeztugo

Yeztugo (lenacapavir) is a completely new class of drug that prevents the HIV-1 infection. Yeztugo is developed by Gilead Sciences and is approved by the FDA as the only injectable that can be administered individually twice a year, with a 6-month interval, for pre-exposure prophylaxis (PrEP). This injection is thought to reduce the risk of acquiring HIV in adults and adolescents who weigh 35 kg or more. This subcutaneous injection should be administered by a healthcare professional. The injectable formulation exhibits a pharmacological activity lasting up to six months, which effectively overcomes the limitations associated with daily oral PrEP regimens, including issues of adherence and pill burden.

FDA approval was supported by evidence from the Phase 3 PURPOSE 1 and PURPOSE 2 clinical trials, which confirmed that over 99.9% of participants remained HIV-negative, providing strong validation of the intervention’s efficacy, which makes it superior to the daily oral PrEP medications. Yeztugo is available as a tablet and an injection dosage form, but the indication of PrEP is only indicated for the injection formulation that is administered twice a year. The development of Yeztugo is a breakthrough in HIV prevention. It is said that it will revolutionize HIV treatment and make it much simpler, lowering the stigma and offering patient acceptance.

Background

Before approval of Yeztugo for PrEP, lenacapavir was marketed under the name of Sunlenca, which was utilized for the treatment of multidrug-resistant HIV-1 infection in heavily treatment-experienced adults. Sunlenca provided a vital therapeutic option for patients with limited treatment choices due to the development of resistance to current treatment or any safety and tolerability issues. Sunlenca was administered as a combination regimen along with previous antiretroviral drugs.

The expansion of lenacapavir’s indications from treatment to prevention states a significant breakthrough in the fight against HIV and gives patients hope and practical solutions.

Mechanism: A novel approach

Lenacapavir is a first-in-class, long-acting capsid inhibitor that targets the HIV-1 capsid protein, a highly conserved structural component essential to multiple stages of the viral lifecycle.

Following viral entry into the host cell, the intact HIV-1 capsid must remain stable as it travels through the cytoplasm to the nuclear pore complex, where uncoating and reverse transcription occur. Lenacapavir stabilizes the capsid structure and prevents its disassembly (uncoating), thereby blocking the nuclear material of the viral genome from incorporating with human DNA. This effectively freezes HIV replication at an early post-entry stage.

In case infection had occurred already, in later stages of the viral replication cycle, lenacapavir disrupts proper capsid assembly during the formation of new virions in infected cells. Interfering with capsid multimerization leads to the production of malformed or immature capsids. The resulting virions are structurally defective and non-infectious, impairing viral maturation and spread.

Through these dual-stage inhibitions, blocking nuclear import in the early stage and preventing correct capsid assembly in the late stage, lenacapavir exerts a potent antiviral effect. Its novel mechanism complements other antiretroviral classes and makes it a valuable option for both treatment and pre-exposure prophylaxis (PrEP), particularly in multidrug-resistant HIV-1 infections.

Clinical trials and approval

The approval of Yeztugo comes from the solid foundation of two phase 3 trials: the Purpose-1 and Purpose-2 trials.

The phase 3 Purpose 1 trial (NCT04994509) was a randomized, double-blind study evaluating the efficacy and safety of lenacapavir for HIV-1 pre-exposure prophylaxis (PrEP) in 5,338 cisgender adolescent girls and young women aged 16–25 years across high-incidence regions of South Africa and Uganda. Participants were randomized in a 2:2:1 ratio to receive twice-yearly subcutaneous lenacapavir injections, daily oral emtricitabine–tenofovir alafenamide (FTC/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (FTC/TDF). The primary endpoint was the incidence of HIV-1 infection. Zero HIV infections were observed in the lenacapavir group over 2134 participants compared to 39 infections among 2136 participants in the F/TAF group and 16 infections among 1068 participants in the FTC/TDF group, respectively.

The Purpose 2 trial (NCT04925752) was a Phase 3, randomized, double-blind study assessing the efficacy and safety of twice-yearly subcutaneous lenacapavir for HIV-1 pre-exposure prophylaxis (PrEP) in 3,265 individuals, including cisgender men, transgender women, and gender-diverse individuals aged ≥16 years. Conducted across multiple global regions, including North and South America, Europe, Asia, and Africa, the trial randomized participants in a 2:1 ratio to receive either lenacapavir injections every 26 weeks or daily oral FTC/TDF. The primary endpoint was HIV-1 incidence. Lenacapavir demonstrated a significantly lower HIV incidence rate, 2 cases in total compared to FTC/TDF’s 9 cases overall, yielding an 89% relative risk reduction versus oral PrEP and a 96% reduction versus background incidence.

Safety profile

Yeztugo (lenacapavir) has demonstrated a robust safety and tolerability profile across both the pivotal Phase 3 Purpose 1 and Purpose 2 trials. In Purpose 1, the majority of participants experienced at least one adverse event (AE), with most being mild or moderate in severity. The most commonly reported adverse reactions were injection site reactions (ISRs), such as nodules, pain, and swelling. These ISRs were generally mild to moderate, decreased with subsequent injections, and led to discontinuation in only a small fraction of participants (0.2%). No significant or new safety concerns were identified, and serious adverse events were rare. Importantly, there were no serious ISRs or deaths attributed to lenacapavir throughout the trial.

Impact and future viewpoint

FDA approval of Yeztugo (lenacapavir) as the first and only twice-yearly injectable HIV prevention drug is a milestone in the battle against HIV, with ≥99.9% efficacy in phase 3 clinical trials. Yeztugo provides a game-changing solution, breaking through the decades-long HIV prevention barriers, such as adherence barriers, stigma, resistance, and the burden of a daily pill. Its long-acting injectable will be well-suited to increase PrEP adherence and retention.

The approval of Yezugo has been welcomed and appreciated by global health organizations such as the World Health Organization. WHO has prepared new guidelines to help countries integrate lenacapavir into their HIV protection strategies. The biannual dosing system of the drug allows revolutionizing the public health approaches by simplifying prevention, reducing the cases of missing the dose, and potentially curbing new HIV infections in the population.

Looking ahead, the impact of Yeztugo will depend on equitable and rapid access, especially in low- and middle-income countries where the HIV burden is highest. Efforts are underway to accelerate regulatory approvals worldwide and to facilitate generic manufacturing, which could further expand access. Researchers are also exploring the potential for even longer-acting formulations and combination regimens, raising the prospect of once-yearly PrEP and broader protection.

Reference

Yeztugo® (Lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection https://www.gilead.com/news/news-details/2025/yeztugo-lenacapavir-is-now-the-first-and-only-fda-approved-hiv-prevention-option-offering-6-months-of-protection

Yeztugo (lenacapavir) FDA Approval History – Drugs.com https://www.drugs.com/history/yeztugo.html

FDA Approves Yeztugo https://www.drugs.com/newdrugs/fda-approves-yeztugo-lenacapavir-first-only-hiv-prevention-option-offering-6-months-protection-6555.html

Twice-Yearly HIV-1 PrEP Yeztugo Gets FDA Approval https://www.infectiousdiseaseadvisor.com/news/twice-yearly-hiv-1-prep-yeztugo-gets-fda-approval/

U.S. FDA Accepts Gilead’s New Drug Applications for Twice-Yearly Lenacapavir for HIV Prevention Under Priority Review https://www.gilead.com/news/news-details/2025/us-fda-accepts-gileads-new-drug-applications-for-twice-yearly-lenacapavir-for-hiv-prevention-under-priority-review

Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/​Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection (PURPOSE 1) https://clinicaltrials.gov/study/NCT04994509

Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024 https://www.gilead.com/news/news-details/2024/full-efficacy-and-safety-results-for-gilead-investigational-twice-yearly-lenacapavir-for-hiv-prevention-presented-at-aids-2024

Gilead’s Twice-Yearly Lenacapavir Demonstrated 100% Efficacy and Superiority to Daily Truvada® for HIV Prevention https://www.gilead.com/news/news-details/2024/gileads-twice-yearly-lenacapavir-demonstrated-100-efficacy-and-superiority-to-daily-truvada-for-hiv-prevention

Gilead’s twice-yearly shot prevents 100% of HIV cases in trial with women  https://www.clinicaltrialsarena.com/news/gileads-twice-yearly-shot-prevents-100-of-hiv-cases-in-trial-with-women/

Long-acting injectable lenacapavir continues to show promising results for HIV prevention https://www.who.int/news/item/26-09-2024-long-acting-injectable-lenacapavir-continues-to-show-promising-results-for-hiv-preventionFDA approval of injectable lenacapavir marks progress for HIV prevention, https://www.who.int/news/item/19-06-2025-fda-approval-of-injectable-lenacapavir-marks-progress-for-hiv-prevention

Bekker LG et al, Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women, N Engl J Med 2024;391:1179-1192, DOI: 10.1056/NEJMoa2407001

Kelley CF et al, Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons, N Engl J Med 2025;392:1261-1276, DOI: 10.1056/NEJMoa2411858

amgen

Amgen’s Once-Monthly Maridebart cafraglutide (MariTide) Demonstrates Strong Efficacy in Obesity: Positive Phase 2 Maritime 1 Trial Results

by with No Comment Clinical Trails

26 June 2025

Category: Clinical Trial I Obesity & Metabolic Disorders I

Diabetes and Weight loss

Written and Reviewed By:

Vikas Londhe, MPharm

Amgen logo

In recent times, the focus has been shifted to next-generation metabolic therapies and innovative molecules that target the body’s hormonal cascades that are involved in hunger, energy burning, and fat storage. Among them, GLP-1 receptor agonists and GIP-based therapies have improved metabolic health. In this space, Amgen made a bold move into weight loss and diabetes treatments with the development of the maridebart-cafraglutide combination branded as MariTide. Amgen released positive Phase 2 results from their Maritime‑1 trial, and the results are published in the New England Journal of Medicine.

MariTide represents first-in-class dual-action molecules, combining glucagon-like peptide-1 (GLP-1) receptor agonism with glucose-dependent insulinotropic polypeptide (GIP) receptor antagonism potential with a synergistic mechanism that modulates insulin sensitivity and lipid metabolism. MariTide is designed to be administered as a once-monthly subcutaneous dose, which will increase patient compliance and convenience. The trial’s results showing up to 20% body weight reduction position MariTide as a major breakthrough in the near future.

Phase 2 Maritime‑1 Trial

The Phase 2 MARITIME-1 trial was a randomized, double-blind, placebo-controlled, dose-ranging study evaluating maridebart cafraglutide (MariTide) in adults with obesity or overweight who had at least one weight-related comorbidity. A total of 592 participants were enrolled into two cohorts: 465 in the obesity cohort (BMI ≥30 or ≥27 with complications, HbA1c <6.5%) and 127 in the obesity–diabetes cohort (BMI ≥27, HbA1c 7–<10%). Participants received subcutaneous MariTide every 4 or 8 weeks for 52 weeks across varying doses (140, 280, or 420 mg), with or without dose escalation, or placebo. The study assessed weight loss efficacy, metabolic improvements, and safety outcomes.

Endpoints

The primary endpoint was the percentage change in body weight from baseline to week 52. Secondary endpoints included proportions achieving ≥5% to ≥20% weight loss and changes in waist circumference, HbA1c, lipid profiles, CRP, and blood pressure. Safety outcomes focused on gastrointestinal adverse events and treatment discontinuation. The study aimed to evaluate both the weight loss efficacy and broader metabolic benefits of maridebart cafraglutide (MariTide).

Results

In the obesity cohort, maridebart cafraglutide led to a mean body weight reduction of −16.3% to −19.9% (efficacy estimand) compared to 2.6% with placebo. In the obesity–diabetes cohort, reductions ranged from −12.1% to −17.0% compared to 1.4% with placebo. More participants achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss with maridebart cafraglutide. Additionally, significant HbA1c reduction and improvements in waist circumference, blood pressure, hs-CRP, and lipid profiles were observed.

Side Effects

In the phase 2 trial, 90–99% (obesity) and 91–97% (obesity–diabetes) of participants on maridebart cafraglutide reported at least one adverse event, versus 68% and 81% with placebo, respectively. Gastrointestinal events (nausea, vomiting, retching and diarrhea) were most common and mostly mild to moderate, with higher rates in no-dose-escalation groups. Discontinuation due to GI events occurred in up to 27% of participants. There were 35 serious adverse events and 2 deaths, both deemed unrelated to treatment.

In the phase 2 trial, maridebart cafraglutide was associated with mild-to-moderate hypersensitivity (5%), increased gallbladder events, and a few cases of level 2 hypoglycemia. Minor mood events, slight increases in heart rate, amylase, lipase, and calcitonin (within normal range), and decreased liver aminotransferase levels were noted. No cases of pancreatitis, diabetic retinopathy, or C-cell hyperplasia occurred.

Mechanism of Action

Maridebart cafraglutide works through a unique combination of actions. It blocks the GIP receptor and activates the GLP-1 receptor using two attached GLP-1 agonist peptides (cafraglutide), which together regulate body weight. This combination helps people feel full for longer, slows the emptying of food from the stomach, and reduces hunger, leading to lower calorie intake. It also improves how the body responds to insulin and controls blood sugar levels, making it useful for people with obesity.

Strategic Phase 3 Maritime Design

Amgen’s MARITIME Phase 3 program is currently in progress, consisting of 72-week chronic weight management studies evaluating maridebart cafraglutide (MariTide). The program includes two parallel trials: Maritime 1, enrolling participants with obesity or overweight with at least one weight-related comorbidity, and Maritime 2, targeting individuals with type 2 diabetes. Additional Phase 3 trials evaluating MariTide in patients with atherosclerotic cardiovascular disease, heart failure, and obstructive sleep apnea are expected to launch in 2025. Initial readouts from the ongoing Phase 3 studies are anticipated in 2027, positioning MariTide as a major therapeutic option in obesity and diabetic care.

Bottom Line

Susan Sweeney, executive vice president of Obesity and Related Conditions at Amgen, said, “Obesity affects all parts of the world and people of all different populations, and the challenge is significant.”

We have witnessed a lot of patients in our surroundings, including society, friends, or family; for them, Maridebart Cafraglutide (MariTide) represents a promising new candidate in the competitive market of obesity and metabolic disease treatment. This is backed by robust Phase 2 results showing significant weight loss, metabolic improvements, and a manageable safety profile. MariTide showed the potential to offer meaningful clinical benefits with a once-monthly dosing regimen. At the bottom line, Amgen’s MariTide could redefine long-acting obesity treatment with its potent efficacy, broad metabolic impact, and patient-friendly dosing.

Reference

Jastreboff AM, Ryan DH, Bays HE et al, Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial, The New England Journal of Medicine, Published June 23, 2025, DOI: 10.1056/NEJMoa2504214

Results from Amgen’s phase 2 obesity study of monthly Maritide presented at the American diabetes association 85th scientific sessions, Amgen, https://www.amgen.com/newsroom/press-releases/2025/06/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions

Inside Amgen’s Phase 3 MARITIME Program: Advancing the Future of Obesity Care, Amgen, https://www.amgen.com/stories/2025/06/inside-amgens-phase-3-maritime-program—advancing-the-future-of-obesity-care

Maridebart Cafraglutide for Chronic Weight Management, iClinique, https://www.icliniq.com/articles/drug-and-supplements/maridebart-cafraglutide#how-does-maridebart-cafraglutide-work-in-obesity-management

Efficacy and Safety of Maridebart Cafraglutide in Adult Participants with Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-2), ClinicalTrials.gov ID NCT06858878, https://clinicaltrials.gov/study/NCT06858878

ChatGPT Image Jun 24, 2025, 11_56_23 AM

“CagriSema: A Powerful New Weight Loss and Diabetes Combination Therapy Emerges from REDEFINE-2 Trial”

by with No Comment Clinical Trails

24 June 2025

Category: Clinical Trial I Obesity & Metabolic Disorders I

Diabetes and Weight loss

Medically Written and Reviewed By:

Vikas Londhe MPharm

ChatGPT Image Jun 24, 2025, 01_04_16 PM
Generative AI

The race to develop new treatments for obesity and type 2 diabetes is getting more and more competitive. To this race, the results of the REDEFINE 2 trial (NCT05394519), published recently in The New England Journal of Medicine (NEJM). The study highlights the powerful potential of a novel combination therapy, CagriSema. This once-weekly subcutaneous treatment, combining cagrilintide (an amylin analogue) and semaglutide (a GLP‑1 receptor agonist), has shown impressive results for weight loss and glycemic control, especially in individuals with both obesity and type 2 diabetes.

Study at a Glance

The REDEFINE 2 trial (Trial No. NCT05394519) is a Phase 3a, multicenter, randomized, double-blind, placebo-controlled study sponsored by Novo Nordisk, conducted across 12 countries in Europe, North America, and Asia. The study was designed to evaluate the efficacy and safety of CagriSema. CagriSema was administered once weekly in dose dose-escalated manner starting from a 0.25 mg dose and increasing stepwise till it reached 2.4 mg for each drug in 16 weeks. The trial enrolled non-insulin-dependent participants aged 18 years or older with a body mass index of 27 kg/m² or more, HbA1c between 7% and 10%, and at least one self-reported unsuccessful dietary effort to lose weight. The lifestyle modifications were also suggested to study participants. Participants were randomly assigned to receive CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) or placebo over a 68-week treatment period, followed by a 7-week follow-up. The primary endpoint was percentage change in body weight and percentage of patients achieving ≥5% weight loss from baseline to week 68; however, additional secondary endpoints included changes in waist circumference, glycated hemoglobin level, systolic blood pressure, and other physical function measures from baseline to 68 weeks. Results from this trial, published in The New England Journal of Medicine, have shown the potential of CagriSema to offer a new standard of care in obesity and diabetes management.

Key Findings

The REDEFINE 2 trial showed that CagriSema led to significantly greater weight loss and better blood sugar control compared to placebo in people with obesity and Type 2 diabetes. After 68 weeks of treatment, patients receiving CagriSema lost an average of 15.7% of their body weight, which was much higher than the placebo group’s 3.1%. In addition, almost 83.6% of patients in the CagriSema group achieved at least 5% weight loss, a clinically significant benchmark, compared to 30.8% in the placebo group. Additionally, a weight reduction of 10% or more occurred in 65.6% of the patients in the cagrilintide–semaglutide group and in 10.3% of in the placebo group; a weight reduction of 15% or more occurred in 43.8% and 2.4%, respectively, and a weight reduction of 20% or more occurred in 22.9% and 0.5%, respectively. CagriSema also showed greater improvement in blood sugar control, reducing average HbA1c levels by 1.8 percentage points, while the placebo reduced them by only 0.4 percentage only.

On average, systolic pressure went down by 4.1 mm Hg more than the placebo group, a statistically significant difference. Additionally, the combination treatment also showed improvements in diastolic blood pressure, C-reactive protein (a marker of inflammation), and cholesterol levels compared to placebo. On average, waist size reduced by 8.3 cm more than the placebo group.

 These results confirmed that the combination therapy offers stronger benefits for both weight and glucose management, especially in patients with diabetes.

Mechanism of Action

Cagrilintide is an amylin analogue, which mimics the action of the natural hormone amylin. It helps to reduce appetite, increase feelings of fullness, and slow down the emptying of the stomach, which leads to reduced food intake and promotes weight loss. It binds to amylin receptors in the brain, specifically in the hypothalamus and other brain regions, to promote feelings of fullness and reduce food intake. On the other hand, semaglutide is a GLP-1 receptor agonist, a class of drugs that stimulates insulin release in response to high blood sugar levels, suppresses glucagon (a hormone that raises blood sugar), and also delays gastric emptying. It plays a dual role in improving glycemic control and enhancing satiety, contributing further to weight reduction. Together, cagrilintide and semaglutide produce synergistic effects.

Safety Profile

CagriSema was generally well tolerated, with a safety profile consistent with what is typically seen with GLP‑1 receptor agonists like semaglutide. The most common side effects reported were gastrointestinal symptoms, including nausea, vomiting, diarrhea, and constipation. These side effects were mostly mild to moderate in severity. A slightly higher number of participants in the CagriSema group discontinued treatment due to side effects compared to the semaglutide and placebo groups. Importantly, no new safety concerns emerged during the trial.

Future Plan

Following the strong results from REDEFINE 2, Novo Nordisk is expected to seek regulatory approval for CagriSema in 2026, supported by earlier data from the REDEFINE 1 trial, which showed an even greater weight loss of 22.7% in people without diabetes. The company is also developing a pre-filled pen for convenient once-weekly dosing, aiming to simplify treatment and enhance patient adherence.

Conclusion and Pharmacally’s Take

CagriSema may emerge as a landmark treatment after approval for diabetes management and obesity care. It combines the benefits of two powerful drugs from their class, offering patients a more effective and synergistic approach to weight and glucose control. This trial proves that individuals with type 2 diabetes, who typically lose less weight than those without, can achieve meaningful and substantial weight loss.

With semaglutide already a blockbuster and tirzepatide on the rise, CagriSema could be the next market capturer in metabolic health and weight loss, especially for patients with complex comorbidities.

References

Davies MJ, Bajaj HS, Broholm C, et al, Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes, The New England Journal of Medicine, Published June 22, 2025, DOI: 10.1056/NEJMoa2502082

A Research Study to See How Well CagriSema Helps People with Type 2 Diabetes and Excess Body Weight Lose Weight (REDEFINE 2), ClinicalTrials.gov ID NCT05394519, https://clinicaltrials.gov/study/NCT05394519

Garvey WT, Blüher M, Contreras CKO, et al, Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity, The New England Journal of Medicine, Published June 22, 2025, DOI: 10.1056/NEJMoa2502081

 

patch

FDA Issues Safety Warning: Transderm Scop (Scopolamine Transdermal System) Antinausea Patch May Cause Heat-Related Illness, Hospitalization, or Death

by with No Comment Disease & Drugs

June 22, 2025
Category: Drug Safety Alerts | FDA Updates | Patient Safety

Written by: Priyanka Khamkar, MPharm

Reviewed By: Pharmacally Editorial Team

patch
Generative AI

The U.S. Food and Drug Administration (FDA) has issued a serious safety communication regarding Transderm Scōp®, a widely used transdermal patch containing scopolamine marketed by Baxter Healthcare Corporation. This transdermal patch is generally prescribed to prevent motion sickness and postoperative nausea. On June 18, 2025, the FDA issued a warning letter that stated that the patch can impair the body’s ability to regulate temperature, potentially causing dangerous heat-related complications, including hospitalization and even death. FDA specifically observed these events in children 17 years and younger and patients who are 60 years and above, who may be sensitive to control body temperature disturbances. The FDA warns Baxter to include this safety information into the label.

What’s the issue?

The scopolamine transdermal patch, typically applied behind the ear, being an anticholinergic drug, inhibits the neurotransmitter acetylcholine, which results in an anticholinergic effect that may suppress the body’s ability to maintain internal pressure and increase the body’s core temperature, and reduce sweating, making it harder to cool down the body. This disrupts thermoregulation and can result in hyperthermia, especially in hot environments or when combined with external heat sources like heated blankets. The FDA observed that the hyperthermia occurs within 72 hours (3 days) after applying the transdermal patch for the first time to the patient; this increases the causal relation between the drug and the event.

The one more thing highlighted by the FDA is that the Transderm Scop patch is only approved for adults, and it is not allowed to be used in children. So it is not an FDA-approved drug for children. However, in some cases, doctors use it as “off-label” in children, like for excessive drooling with cerebral palsy or other neurologic disorders.

Real-World Cases

A review of safety data by the FDA received worldwide since August 2024 revealed that 13 cases of hyperthermia were directly linked to the scopolamine patch use. The onset of reaction, mostly within 72 hours after patch application, confirmed the causal relationship between the scopolamine patch and hyperthermia. Out of these 13 cases, 8 cases involved children equal to or less than 17 years of age, and 4 cases involved older adults (≥60 years). 6 patients were hospitalized; however, 2 deaths were reported in one pediatric and one geriatric patient. In several cases, body temperatures increase above 105°F (40.5°C).

Understanding the Mechanism

Scopolamine works by blocking acetylcholine, a neurotransmitter involved in many involuntary body functions, including sweating. By reducing sweating, scopolamine can unintentionally cause core body temperature to rise, especially in

  • Hot weather
  • Feverish illness
  • Dehydrated states
  • Use of heat-generating devices

When the body failed to cool down on its own by the process of sweating, the inner temperature of the body started to increase. The consequences of increased temperature can range from mild confusion and disorientation to loss of consciousness, coma, or even death.

FDA Instructions

After finding these cases, the FDA instructed Baxter Healthcare Corporation to include these safety findings in the label. The label should mention the risk of hyperthermia resulting in serious harm, along with vulnerable population groups of children below 17 years of age and elderly patients above 60 years. The label should instruct patients to remove the patch as soon as their body temperature increases and if they are not experiencing sweating, even if they are in a warm environment.

FDA Guidance: What Patients and Providers Need to Know

The FDA warns patients and caretakers that during use of the Transderm Scop patch, the following instructions should be followed:

  • Monitor the signs of hyperthermia: flushed skin, lack of sweating, dizziness, confusion, or unusual fatigue.
  • Avoid heated environments and external heat sources (e.g., heated blankets, direct sun exposure).
  • If symptoms appear, immediately remove the patch and seek medical attention.
  • Be aware that side effects can persist for hours or days after patch removal, as the absorbed medicine remains in the body until it’s eliminated.
  • As the long-term use of the patch or use in children is not allowed, the caretaker or patient should consult with a healthcare professional before starting this therapy.

For Healthcare Professionals

  • Warn patients and caregivers about the risk of hyperthermia while prescribing, especially in the vulnerable populations of young children and older people. This population is more susceptible to thermoregulatory changes
  • Instruct patients to remove the patch and consult with a healthcare provider if they experience any hyperthermia symptoms.
  • The prescriber should make the patient aware of the fact that even if they remove the patch, the symptoms may persist as the medicine remains in the body for hours or days.

Quick Safety Checklist

Do

Don’t

Apply the patch only as directed

Use in children without medical guidance

Monitor the signs of hyperthermia

Exposure to heat sources or wear in high temperatures

Remove the patch if hyperthermia signs occur

Ignore early symptoms like dizziness or fatigue

Inform your doctor about side effects and symptoms

Long-term use of patch

Conclusion & Pharmacally’s Take

At Pharmacally, we encourage patient education and informed usage of medications, especially those with powerful systemic effects like anticholinergics. The FDA warning related to the scopolamine transdermal patch highlights how even commonly prescribed drugs can carry rare but serious risks.

All patients and caretakers should stay vigilant, follow proper application guidelines, and communicate any concerns with healthcare providers immediately. For clinicians, it is important to check the benefit-risk balance of the scopolamine patch in vulnerable populations, and in risky conditions, they should consider safer alternatives if available.

References

FDA adds warning about serious risk of heat-related complications with antinausea patch Transderm Scōp (scopolamine transdermal system), US FDA, 18 June 2025, https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-warning-about-serious-risk-heat-related-complications-antinausea-patch-transderm-scop#:~:text=FDA%20is%20warning%20that%20the,instances%20from%20heat%2Drelated%20complications.

Drug Safety Communication, US FDA, https://www.fda.gov/media/187121/download?attachment

Highlights of prescribing information, Transderm scōp, https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/017874s053lbl.pdf

Ms. Priyanka Khamkar is a skilled medical writer at Pharmacally.com with a strong academic foundation, holding an M.Pharmacy in Pharmacology and a GPAT exam qualified. Passionate about research and evidence-based writing, she brings clarity and precision to complex medical topics. Her core interests lie in drug safety, clinical research, and translating science into accessible healthcare content.
freepik__artistic-representation-of-clostridioides-difficil__32689

Ibezapolstat: AcurX Pharmaceuticals First-in-Class Mechanism Antibiotic for Clostridioides difficile Infection Shows Promising Results in Phase 2b Trial

by with No Comment Clinical Trails

Published On: 20 June 2025

Category: Clinical Trial I Infectious Disease I

Gut and Gastrointestinal Infections

Written By: Pharmacally Medical News Desk

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Source: Freepik.com

Clostridioides difficile infection (CDI) is among the most challenging hospital-acquired infections globally. C.Difficile, known for its high recurrence rates and significant impact on the gut microbiome. To date, vancomycin has long been a standard treatment; however, it lacks selectivity and often disrupts beneficial gut bacteria, which contributes to relapses.

Ibezapolstat, a first-in-class antibiotic being developed by AcurX Pharmaceuticals, aims to decipher these issues. Unlike traditional broad-spectrum agents, Ibezapolstat specifically targets DNA polymerase IIIC, an enzyme essential for the replication of Gram-positive bacteria like C. difficile, which is absent in beneficial anaerobic flora.

The recently published Phase 2b clinical trial results in The Lancet Microbe mark a crucial step forward in this drug’s journey, offering new hope in reducing recurrence and treating serious hospital-acquired infections like Clostridioides difficile.

The Phase 2b Trial: Design & Goals

AcurX Pharmaceutical recently concluded its phase 2b trial, and the results are published in Lancet Microbes. The trial was conducted across 15 U.S. centers between March 2021 and October 2023. The randomized, double-blind, active-controlled trial enrolled adults aged 18 to 90 with confirmed C. difficile infection. Patients were randomly assigned to receive

  • Ibezapolstat 450 mg orally every 12 hours (n = 18 total; 16 included in the efficacy analysis)
  • Vancomycin 125 mg orally every 6 hours (n = 14)

The primary objective was clinical cure at the end of treatment (EOT), defined as the resolution of diarrhea and no need for further CDI therapy 48 hours post-treatment.

Efficacy: A Match for Vancomycin

In the Phase 2b clinical trial, ibezapolstat demonstrated clinical efficacy that was analogous to vancomycin, which is the current standard of care for Clostridioides difficile infection. Among the patients evaluated in the trial, 94% of patients treated with ibezapolstat achieved complete clinical cure at the end of treatment, while 100% of patients receiving vancomycin met the same endpoint. This slight numerical difference was not statistically significant and met the criteria for non-inferiority, establishing Ibezapolstat as an equally effective treatment option. More compelling, however, were the findings from a pooled analysis of data from both the Phase 2a and 2b trials. In pooled analysis, done from the combined dataset of Phases 2a and 2b, ibezapolstat achieved a clinical cure rate of 96%. Surprisingly, ibezapolstat sustained a cure rate of 100%, meaning no recurrences were observed one month after treatment. This is in contrast to historical data for vancomycin, where recurrence rates range from 26% to as high as 58%. These results position ibezapolstat not only as an equally effective treatment as vancomycin for acute CDI but also as a promising candidate for reducing the risk of relapse, a critical issue in current CDI management.

Microbiome and Bile Acid Profiles

Even if ibezapolstat showed comparable clinical efficacy to vancomycin, ibezapolstat shows significant advantages over vancomycin in terms of protecting gut health, which is an essential factor in preventing recurrent infections. One of the prominent findings from the study was the rapid microbiological clearance of C. difficile, with 94% of patients treated with ibezapolstat showing eradication of the organism by Day 3, compared to 71% in the vancomycin group. But the main differentiation lies in ibezapolstat’s ability to save the beneficial gut microbiota. Unlike vancomycin, which broadly disrupts the intestinal flora, ibezapolstat preserved vital bacterial groups such as the Firmicutes and Actinobacteria phyla known for supporting immune function and maintaining colonization resistance. This preservation of the microbiome might play a role behind why Ibezapolstat showed zero recurrence rates.

Additionally, stool analysis revealed that ibezapolstat favorably altered bile acid profiles, reducing primary bile acids (which promote C. difficile germination) and increasing secondary bile acids (which inhibit it). This bile acid shift further enhances the gut’s natural defense against reinfection.

These microbiome and metabolomic findings highlight ibezapolstat’s potential not just to treat CDI effectively, but to do so in a way that supports long-term gut health and prevents recurrence, something current therapies generally fail to achieve.

Safety & Pharmacokinetics

Ibezapolstat demonstrated a favorable safety profile in the Phase 2b trial. No drug-related serious adverse events, treatment discontinuations, or deaths were reported in either the ibezapolstat or vancomycin treatment groups.

Pharmacokinetic analysis further supported its targeted mechanism of action, with ibezapolstat achieving high concentrations in stool exceeding 1,000 μg/g by days 8 to 10 while showing minimal systemic absorption. This gut-localized exposure is particularly advantageous in treating C. difficile infections, as it maximizes local antimicrobial activity while minimizing the risk of systemic side effects or toxicity.

The Unique Mechanism of Action

Unlike vancomycin, which largely disrupts bacterial cell wall synthesis and also affects a wide range of gut bacteria due to its common mechanism pathway through inhibiting cell wall synthesis, ibezapolstat offers a more targeted line of attack. It selectively inhibits DNA polymerase IIIC (PolC), an enzyme essential for the replication of Gram-positive pathogens like C. difficile but absent in human cells and many beneficial gut bacteria. This precision targeting enables ibezapolstat to kill C. difficile effectively while showing mercy on much of the gut’s healthy microbiota. As a result, it minimizes disruption to colonization resistance, the gut’s natural defense against reinfection. This selective mechanism is increasingly being recognized as the gold standard in modern antimicrobial development, aligning efficacy with microbiome preservation.

The Road to Approval

Ibezapolstat has already received the U.S. FDA Qualified Infectious Disease Product (QIDP) and Fast Track designations, accelerating its development and review timeline. At the same time, the European Medicines Agency (EMA) has recognized AcurX Pharmaceuticals with Small and Medium-sized Enterprise (SME) status, offering additional guidance and regulatory incentives. A global Phase 3 trial is currently in development and is expected to enroll over 600 patients. This pivotal study will compare ibezapolstat directly with vancomycin in a larger and more diverse population to confirm its efficacy and safety on a broader scale. A crucial regulatory meeting with the FDA is scheduled for mid-2025 to finalize the Phase 3 development plan and determine the path toward potential market approval.

Conclusion & Pharmacally Take

Current treatments for CDI have improved outcomes, but eradicating C. Difficile, preventing recurrence, and protecting other gut microbiomes continue to be major hurdles, “but ibezapolstat offers a new hope in this direction. With its narrow-spectrum precision, gut microbiome-sparing effects, and potential to prevent relapse, it addresses the shortcomings of traditional CDI therapies like vancomycin.

If Phase 3 results confirm these findings, ibezapolstat could emerge not just as an alternative but as a preferred first-line therapy for initial and recurrent CDI.

At Pharmacally, we’re closely watching ibezapolstat’s development as a milestone in microbiome-conscious antibiotic therapy. Its success could pave the way for a new era of targeted antimicrobials that treat without extra damage.

References

Taryn A Eubank, Jinhee Jo, M Jahangir Alam, et al, Efficacy, safety, pharmacokinetics, and associated microbiome changes of Ibezapolstat compared with vancomycin in adults with Clostridioides difficile infection: a phase 2b, randomised, double-blind, active-controlled, multicentre study, Lancet Microbe 2025, https://doi.org/10.1016/ j.lanmic.2025.101126

Acurx Announces Publication in Lancet Microbe of Phase 2b Clinical Trial Data for Ibezapolstat in CDI, AcurX pharmaceuticals, 17 June 2025, https://www.acurxpharma.com/news-media/press-releases/detail/111/acurx-announces-publication-in-lancet-microbe-of-phase-2b

Acurx Announces Publication in Lancet Microbe of Phase 2b Clinical Trial Data for Ibezapolstat in CDI, PRNewswire, 17 June 2025, https://www.prnewswire.com/news-releases/acurx-announces-publication-in-lancet-microbe-of-phase-2b-clinical-trial-data-for-ibezapolstat-in-cdi-302483504.html

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Venclexta Falls Short in Late-Stage Trial for Higher-Risk Myelodysplastic Syndrome (MDS): Roche and AbbVie Release Results

by with No Comment Disease & Drugs

Published: June 18, 2025

Category: Clinical Trial | Hematology | Oncology

Written By: Team Pharmacally    

                                                                                        

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Source: Freepik.com

In the latest development surrounding Venclexta (venetoclax), a flagship hematology drug from the Roche and AbbVie alliance, it has failed to attain its primary endpoint in a critical Phase III study for higher-risk myelodysplastic syndrome (MDS), announced by Roche-Abbvie Alliance on June 16 2025. This marks the second major trial setback for AbbVie and Roche with Venclexta. The drug had previously failed to meet its endpoints in the CANOVA study, which evaluated its use in relapsed or refractory multiple myeloma patients who tested positive for a specific biomarker and had undergone at least two prior lines of therapy

Trial Summary

The VERONA trial was a global, Phase III, randomized, double-blind study involving approximately 500 patients diagnosed with newly diagnosed higher-risk myelodysplastic syndrome (MDS). The trial compared venetoclax (400 mg on Days 1–14) in combination with azacitidine (75 mg/m²) versus azacitidine with placebo, administered in 28-day induction cycles. The study’s co-primary endpoints were complete remission (CR) rate and overall survival (OS). Despite earlier encouraging data from Phase 1b studies, the VERONA trial did not meet its primary endpoint. The trial failed to demonstrate a statistically significant improvement in overall survival when venetoclax was added to standard therapy. As of now, key outcome metrics such as the hazard ratio (HR), median OS values, and p-values have not yet been publicly disclosed. More detailed data are anticipated at upcoming scientific meetings or in peer-reviewed publications.

Despite initial promise and prior regulatory recognition, including an FDA Breakthrough Therapy Designation for various other ailments, the combination therapy did not result in a statistically significant improvement in overall survival in higher-risk MDS patients, which was the trial’s primary goal.

About Myelodysplastic Syndrome (MDS)

Myelodysplastic syndrome, also known as myelodysplasia or myelodysplastic neoplasm, is a group of conditions, mostly of cancerous etiology, that affect bone marrow and its ability to produce mature and healthy blood cells like RBCs, platelets, and WBCs. A result of a lack of mature cells in the blood leads to conditions like anemia, frequent bleeding, and infections; in some cases, patients may develop acute myeloid leukemia. Patients with higher-risk MDS face a poorer prognosis, with limited frontline therapeutic options beyond supportive care and hypomethylating agents like azacitidine.

Venclexta is a selective B-cell lymphoma 2 (BCL-2) inhibitor. In some blood cancers, BCL-2 prevents cancer cells from undergoing apoptosis, a natural death or self-destruction process. Venclexta inhibits the BCL-2 protein and works to help restore the process of apoptosis. It was being evaluated to determine whether it could drive deeper remissions and improved survival in this underserved patient population.

Venclexta’s Standing in Other Indications

It’s important to note that despite the VERONA trial setback for MDS, Venclexta (venetoclax) remains FDA-approved and widely used in the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), specifically in adult patients who are unfit for intensive chemotherapy. The drug continues to hold an important place in modern hematology, having generated over $2.6 billion in global sales in 2024, which underscores both its clinical relevance and broad adoption in real-world practice.

Clinical Implications

While the outcome of the VERONA trial is disappointing, it provides meaningful insights for both clinicians and researchers. Even though the Venclexta is already approved for AML, The results underscore the distinct biological complexities between MDS and AML, despite their clinical similarities. As Venclexta was emerges as the hope for MDS patient after its positive phase I result, but failure of phase III study highlight the urgent and continuing need for effective frontline treatment options for patients with higher-risk MDS. On the safety front, no new adverse signals were reported, although a full safety profile will be presented at upcoming medical conferences.

In response to the trial results, Roche and AbbVie released a joint statement, saying, “Although this outcome is not what we hoped for, we remain committed to exploring novel therapeutic strategies in MDS and other hematologic malignancies.”

Conclusion and Pharmacally Perspective

The failure of Venclexta in the VERONA trial represents a disappointing moment in the pursuit of better treatments for higher-risk myelodysplastic syndromes. Yet, in science, not all setbacks are dead ends. This trial underscores the biological complexity of MDS and the ongoing need for innovation in hematologic oncology. For AbbVie and Roche, it offers lessons to refine future therapeutic approaches. For clinicians and patients, it reinforces the importance of rigorous, data-driven advancement.

At Pharmacally, we believe that every clinical trial, whether successful or not, contributes to the greater mission of advancing smarter, safer, and more targeted care. We will continue to monitor developments in this space and report on emerging therapies, translational research, and key regulatory updates that shape the future of blood cancer treatment

Reference

Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome (Verona). http://clinicaltrials.gov/study/NCT04401748

Venclexta (venetoclax), Package Insert https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208573s013lbl.pdf

AbbVie Provides Update on VERONA Trial for Newly Diagnosed Higher-Risk Myelodysplastic Syndromes, PRNewswire, https://www.prnewswire.com/news-releases/abbvie-provides-update-on-verona-trial-for-newly-diagnosed-higher-risk-myelodysplastic-syndromes-302481869.html?utm_source=chatgpt.com

Roche, AbbVie say trial of Venclexta in patients with myelodysplastic syndromes falls short, Fierce Pharma, https://www.fiercepharma.com/pharma/roche-abbvie-trial-venclexta-patients-myelodysplastic-syndromes-falls-short

Genentech Provides Update on Phase III Verona Study, Genentech, A member of the Roche Group, https://www.gene.com/media/press-releases/15068/2025-06-16/genentech-provides-update-on-phase-iii-v?utm_source=chatgpt.com

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After Second Liver Failure Death, Sarepta Therapeutics Halts Global Elevidys Dosing in Non-Ambulatory Duchenne Muscular Dystrophy Patients; Phase III ENVISION Trial Impacted

by with No Comment Disease & Drugs

Medically Written and Reviewed By:

Vikas Londhe, MPharm

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Source: Freepik.com

On June 15, 2025, Sarepta Therapeutics announced the second death of a teenage male patient linked to acute liver failure (ALF) following its one-time gene therapy drug Elevidys in a non ambulatory Duchenne Muscular Dystrophy (DMD) patient, someone who is no longer able to walk due to this condition. The first fatality occurred in March 2025, when a 16-year-old boy succumbed to liver failure months after his treatment with Elevidys.

Official response

As soon as Sarepta was aware about adverse event, they suspended all commercial shipments of Elevidys to non‑ambulatory patients. Sarepta has completely paused dosing to non-ambulatory patient cohort in ENVISION Phase III trial which is going on in ambulatory and non-ambulatory older patient globally; as they are focusing on designing and enhancing more acceptable immunosuppressant regimen along with Elevidys.

Sarepta summon an independent panel of DMD and liver experts to evaluate alternate therapies like sirolimus in combination with corticosteroids to mitigate liver failure risk.

Alongside, Sarepta is continuously discussing with the FDA and other regulatory bodies their proposed plan for this event.   

Roche, which is partnered with Sarepta and is responsible for Elevidys’ marketing outside the United States, has equally halted dosing and shipments of Elevidys for non‑ambulatory patients globally.

Sarepta has particularly reported that both fatalities were associated with non-ambulatory patients who were no longer able to walk, a subgroup with advanced DMD. Approximately 140 such patients have been treated, and now, with two ALF-related deaths, this is considered to be a serious safety signal.

However ambulatory patients (those still walking) can continue treatment under the current corticosteroid regimen, as company has not amended protocols for them.

Elevidys & liver risk

Elevidys (delandistrogene moxeparvovec) is an innovative gene therapy that uses an Adeno-Associated Virus (AAV) as a delivery system to transport a micro‑dystrophin genetic material into the body via a single IV infusion. AAV-based gene therapies are known to cause acute liver injury, which can lead to liver failure, though fatalities were rare.

The Elevidys’ previous FDA approval already requires corticosteroid administration one day before initiating treatment and continuing for 60 days post-administration, along with close monitoring for liver function, but those measures have not prevented these rare, severe outcomes. Sarepta is now working on an enhanced safety regimen, which may include the addition of the extra immunosuppressant drug sirolimus into the current corticosteroid regimen. This modification of treatment is held up by preclinical data, which demonstrated sirolimus’ effectiveness in suppressing certain liver enzymes, which may help to mitigate this potential safety signal.

Implications for patients and the market

The tragic loss of two non-ambulatory patients highlights the importance of carefully analyzing Elevidys’s further benefits against the serious risks of liver failure in this subgroup. The ENVISION trial will be amended to include stronger immunosuppressant protocols by the addition of sirolimus; however, this change must receive FDA clearance before dosing resumes. While the FDA has agreed to the pause and is reviewing emerging safety data, full restoration of the trial and treatment depends on how effectively Sarepta is mitigating liver risk in non-ambulatory patient populations.

Summary

Sarepta Therapeutics has reported a second death from acute liver failure in a non-ambulatory patient treated with its Duchenne Muscular Dystrophy gene therapy, Elevidys. Both fatalities occurred in patients who were no longer able to walk, prompting Sarepta and its partner Roche to suspend dosing and commercial shipments of Elevidys for this subgroup globally; however, treatment continues for ambulatory patients. For the time being, dosing to the non-ambulatory cohort group in the Phase III ENVISION trial is on hold pending regulatory review of enhanced immunosuppressant protocols, possibly for the addition of sirolimus into the regimen. The company is working with an independent panel of experts to evaluate stronger liver-protection strategies. These developments have deepened inspection of Elevidys’s safety profile, particularly in advanced-stage DMD. At the same time, it is raising questions about gene therapy risks.

References

Sarepta Community Letter: Safety Update regarding Elevidys in non-ambulatory individuals with Duchenne, Sarepta Therapeutics, June 15, 2025, https://www.parentprojectmd.org/wp-content/uploads/2025/06/Elevidys-Community-Letter-6.15.2025.pdf

Highlights of prescribing information, Elevidys, https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-ELEVIDYS_1.pdf

Sarepta Reports Second Death of Patient Using Its Gene Therapy, Bloomberg, https://www.bloomberg.com/news/articles/2025-06-15/sarepta-reports-second-death-of-patient-using-its-gene-therapy

Sarepta reports second case of liver failure death after its gene therapy treatment, Reuters, https://www.reuters.com/business/healthcare-pharmaceuticals/sarepta-reports-second-case-liver-failure-death-after-its-gene-therapy-treatment-2025-06-15/

A safety update on Elevidys, June-2025, Parent Project Muscular Dystrophy, https://www.parentprojectmd.org/a-safety-update-on-elevidys-june-2025/?utm_source=chatgpt.com

Second DMD Patient Dies after Treatment with Sarepta Gene Therapy, https://www.genengnews.com/topics/genome-editing/second-dmd-patient-dies-after-treatment-with-sarepta-gene-therapy/

Sarepta Provides Safety Update for ELEVIDYS and Initiates Steps to Strengthen Safety in Non-Ambulatory Individuals with Duchenne, Sarepta Therapeutics, https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-provides-safety-update-elevidys-and-initiates-steps

2148920822

Moderna Launches mNEXSPIKE: New FDA-Approved COVID Vaccine for High-Risk Groups

by with No Comment New Drug Approval

Written By: Dewanshee Ingale, BPharm

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Source: Freepik.com

In a landmark move, the FDA has granted approval to Moderna’s mNEXSPIKE, marking a new chapter in COVID-19 vaccine evolution. Approved on May 30, 2025, was a historic landmark towards the continuous development and evolution of messenger RNA (mRNA) technology based vaccines. The vaccine is such created that it acts as a next generation booster to improve the COVID-19 protection primarily focusing on the high-risk people. High risk populations include older adults from the age of 65 and above as well as smaller adults from the age of 12-24 with serious medical conditions defined by the Centres’ for Disease Control and Prevention (CDC) and that can increases the worsening of the outcomes if they are infected by virus. With the grand approval, Moderna now expects to provide mNEXSPIKE in addition to its original Spikevax® vaccine during this upcoming 2025-2026 respiratory virus season.          

Present data and background

COVID-19 still serves as a major public health risk in the world. In 2024, the virus took more than 47,000 lives in America, which translates to a death every 11 minutes. Older adults usually experience very severe sickness, hospitalization, and death as compared to other groups. CDC surveillance data from October 2023 to April 2024 show that this older age group represented 70% of adult hospitalizations. Adults aged 65 and older comprised approximately 70% of all COVID-19-related hospitalizations among adults in the U.S. Among the adults who died in the hospital due to COVID-19, 80% were aged 65 and above.

The high prevalence of certain medical conditions further compounds this vulnerability. For example, obesity may increase the risk of severe COVID-19 outcomes by 1.4 times, diabetes by 1.8 times, and chronic lung diseases by as much as 3.2 times. These conditions significantly raise the likelihood of serious health complications. This data underscores the urgent need for effective and targeted vaccination strategies such as Moderna’s next-generation mNEXSPIKE vaccine to protect those most at risk, especially as the COVID-19 virus continues to evolve.

mNEXSPIKE is built upon Moderna’s mRNA-1273 (Spikevax) platform, but with an updated design, which primarily focusing on the key regions of the SARS-CoV-2 spike protein instead of targeting the whole structure. This invention, when combined with a lower dose (10 µg vs. Spikevax’s 50 µg), aims to improve efficiency while reducing reactogenicity. The development of mNEXSPIKE was guided by real-time data and advancements in prognostic analytics, reflecting Moderna’s commitment to continuous innovation and optimization.

A Novel Approach

Moderna’s mNEXSPIKE characterizes an important step ahead in COVID-19 vaccine. It is created on the basic foundation of mRNA technology but is designed in such a way that it is more efficient and can address present and future challenges as compared to previously present COVID-19 vaccines. mNEXSPIKE offers an enhanced mRNA technique that targets the specific region of the SARS-CoV-2 spike protein. This enables the human’s immune system to react strongly while it delivers a significantly low dose at 10 micrograms, which is one-fifth of the dose of Moderna’s original Spikevax vaccine.

The lowered-dose formulation is not only responsible for reducing the side effects but also for rationalizing manufacturing and distribution. mNEXSPIKE can be stored at regular refrigerator temperatures (2-8°C) for 90 days, overcoming the logistical difficulties of the prior existing mRNA vaccines and enabling use in a wide geographic area, particularly in areas where the facility of cold storage does not exist.

Individuals who have already received the COVID-19 vaccine are advised to use this vaccine as a booster vaccine to protect adults 65 years and above or 12-64 years old with other comorbidities. Clinical trials have established that this new vaccine offers more protection or equivalent protection in comparison to the previously existing vaccine. A stronger immune response is elicited against both the Omicron subvariants and the original virus strain.

With a designed antigen, reduced doses, and improved storage stability, mNEXSPIKE bears a very clever strategy for pandemic protection. This leads to increased efficiency, adaptability, and patient friendliness for those who are at risk. 

Clinical trials and approval

Rigorous clinical trial data support the FDA approval of Moderna’s mNEXSPIKE COVID-19 vaccine, which represents efficacy and safety in different populations. The efficacy and safety of mNEXSPIKE were evaluated in a randomized, active-controlled NextCOVE clinical trial (NCT05815498) that was conducted in the United States, the United Kingdom, and Canada. The conducted large-scale evaluation included 11,417 individuals who were aged 12 years and above, with a median follow-up of 8.8 months.

The study population was distinct, with an average age of 56 years (range: 12-96 years). Demographically, the trial included

8.7% adolescents (12-17 years)

62.6% of adults (18-64 years)

28.7% older adults (65+ years)

The NextCOVE trial enrolled participants who were evenly divided between the mNEXSPIKE group (n = 5,706) and the comparator vaccine group (n = 5,711). Nearly all participants had received at least one prior COVID-19 vaccine dose, with an average interval of 9.8 months since their most recent vaccination. Notably, 74.3% of participants showed evidence of prior SARS-CoV-2 infection at baseline.

The mNEXSPIKE vaccine used in the study was a bivalent formulation, delivering a 10 microgram total dose comprising 5 µg targeting the original SARS-CoV-2 (Wuhan strain) and 5 µg targeting the Omicron variant. This represents a substantial dose reduction compared to the 50 µg dosage of the comparator vaccine. Participants received a single 0.2 mL intramuscular injection, administered at least three months after their previous COVID-19 vaccine dose.

Results

The primary endpoint of the NextCOVE Phase 3 trial (NCT05815498) was to evaluate the efficacy of Moderna’s mNEXSPIKE (mRNA-1283) vaccine in preventing symptomatic COVID-19, starting 14 days after a single booster dose, compared to the existing Spikevax (mRNA-1273) vaccine. The study enrolled over 11,400 participants aged 12 years and older, with nearly all having received at least one prior COVID-19 vaccination. The results demonstrated that mNEXSPIKE met the criteria for non-inferiority to Spikevax and showed a relative vaccine efficacy (rVE) of 9.3% in preventing symptomatic COVID-19 across all adults. Notably, in adults aged 65 and older, mNEXSPIKE showed an even higher rVE of 13.5%, indicating stronger protection in this high-risk group. The vaccine was also well tolerated, with a safety and reactogenicity profile comparable to or slightly improved over Spikevax, despite using a significantly lower dose of just 10 µg (versus 50 µg for Spikevax).

Safety profile

Moderna’s mNEXSPIKE has established a favorable safety profile across all age groups, with most side effects being mild to moderate and transient. Commonly reported adverse reactions included pain at the injection site, fatigue, headache, muscle pain, joint pain, chills, and nausea or vomiting, with slightly lower frequencies observed in adults aged 65 and older.

A key safety consideration is the rare risk of myocarditis and pericarditis, particularly in males aged 12–24 years, typically occurring within one week of vaccination. The estimated rates are approximately 8 cases per million doses in recipients under 64 years and 25 per million in males aged 12–25.

The vaccine is contraindicated in individuals with a history of severe allergic reactions (e.g., anaphylaxis) to any mNEXSPIKE component or prior Moderna COVID-19 vaccine dose. Syncope may also occur post-vaccination, as seen with other injectables.

Overall, the safety profile of mNEXSPIKE is consistent with other mRNA vaccines, and combined with its 9.3% higher relative vaccine efficacy, especially in older adults, it is a strong candidate for protecting high-risk populations during the ongoing COVID-19 threat.

Impact and future viewpoint

The sanction of Moderna’s mNEXSPIKE COVID-19 vaccine demonstrates an important invention in the pandemic protection, particularly for high risk groups like elderly people and those who have comorbidities. mNEXSPIKE offers an improved efficiency at a reduced dose and storage requirements, and is expected to increase the accessibility of vaccines and uptake, usually in areas with limited cold storage requirements. The vaccine’s improved safety and effectiveness characteristics are likely to reduce the total number of hospitalizations and deaths caused the COVID-19 which has taken thousands of lives in the U.S. over a year.

Looking at the future, mNEXSPIKE has undoubtedly set an entirely new standard for the upcoming next-generation vaccines, showcasing the potential for design and innovation that can protect the vulnerable population better. The approval also depicts the transformation toward personalized and adaptable vaccine planning strategies, which are of utmost importance due to the continuous evolution of the virus.

Overall, the newly created booster vaccine, Moderna’s mNEXSPIKE, is not only capable of strengthening the present pandemic preparedness but also lays the way for future innovation in mRNA vaccine technology and protection of public health.

References

mNEXSPIKE FDA Approval History https://www.drugs.com/history/mnexspike.html

Introducing mNEXSPIKE: Moderna’s New COVID-19 Vaccine https://www.modernatx.com/media-center/all-media/blogs/introducing-mnexspike-modernas-new-covid-19-vaccine

Moderna Receives U.S. FDA Approval for COVID-19 Vaccine mNEXSPIKE https://investors.modernatx.com/news/news-details/2025/Moderna-Receives-U-S–FDA-Approval-for-COVID-19-Vaccine-mNEXSPIKE/default.aspx

FDA approves Moderna’s new COVID-19 vaccine https://www.cidrap.umn.edu/covid-19/fda-approves-modernas-new-covid-19-vaccine

FDA Package Insert – MNEXSPIKE  https://www.fda.gov/media/186738/download

Spyros Chalkias, Antionette Pragalos, Adebayo Akinsola, et al, Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain and N-Terminal Domain mRNA Vaccine, The Journal of Infectious Diseases, Volume 231, Issue 4, 15 April 2025, Pages e754–e763, https://doi.org/10.1093/infdis/jiaf022

A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 (NextCOVE), moderna clinical trials, https://trials.modernatx.com/study/?id=mRNA-1283-P301&Latitude=27.6648274&Longitude=-81.5157535&LocationName=Florida,%20USA&MileRadius=100

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

104939

The Hidden Pain Pathway: Paracetamol (Acetaminophen) Metabolite AM404 Blocks Peripheral Sodium Channels – A New Mechanism Uncovered

by with No Comment Research

Medically Written and Reviewed By: Vikas Londhe, M.Pharm, Pharmacology

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Source: Freepik.com

For over a century, paracetamol (acetaminophen) has been one of the world’s most widely used analgesics and antipyretics. Despite its widespread use, its exact mechanism of action has remained unclear. It was long believed to work mainly by blocking certain enzymes called cyclooxygenases (COX), especially COX-2. These enzymes are responsible for producing prostaglandins, which are chemicals that promote pain, inflammation, and fever. By reducing prostaglandin production, paracetamol helps lower pain and fever without significantly reducing inflammation like other NSAIDs. However, it is believed that paracetamol is only effective in mild inflammations, like after tooth extraction, and it is not effective in severe inflammation that arises from rheumatoid arthritis and acute gout.

Another pathway involves the TRPV1 receptor, short for Transient Receptor Potential Vanilloid 1, which plays a role in sensing heat and pain. Some research suggests that an active metabolite of paracetamol, the fatty acid amide N-arachidonoylphenolamine (AM404), may activate TRPV1 in a way that leads to pain relief by desensitizing these pain-sensing receptors.

However, new research conducted at Hebrew University of Jerusalem and the findings are published in The Proceedings of the National Academy of Sciences (PNAS) has uncovered a previously unknown mechanism of paracetamol. The new research proposed that paracetamol acts directly at peripheral nerve endings. Its metabolite AM404 can block sodium channels in the nerves, which are essential for sending pain signals to the brain. This discovery adds a new dimension to our understanding of how paracetamol relieves pain: not just through the inhibition of certain enzymes and receptors, but also by directly inhibiting the body’s ability to send pain signals to the brain.

The Breakthrough Study

A team led by Professors Alexander Binshtok and Avi Priel from the Hebrew University of Jerusalem published these game-changing findings in the prestigious PNAS, titled “The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels”

The key findings of the Research Includes

Local production of AM404: After oral intake of paracetamol, the body converts it to p-aminophenol in the liver, which is subsequently transformed into AM404 by fatty acid amide hydrolase (FAAH) in primary sensory neurons, essentially at the nerve endings where pain signals originate.

Inhibition of nociceptive sodium channels: AM404 directly blocks voltage-gated sodium channels Na_V1.7 and Na_V1.8, both crucial for generating action potentials in pain-sensing neurons. The blockade occurs via the local anesthetic binding site.

Peripheral analgesia: Through this localized mechanism, AM404 prevents pain signals at their source, producing potent relief in both regular and inflammatory pain models in rodents.

Researchers found that AM404, a metabolite formed from paracetamol in the body, accumulates in peripheral sensory neurons where it directly inhibits voltage-gated sodium channels Na_V1.7 and Na_V1.8. These channels are critical for the initiation and conduction of pain signals at the site of injury or inflammation. By blocking these sodium channels, AM404 effectively diminishes nociceptive signal transmission at its source, preventing pain before it even reaches the spinal cord. This peripheral action represents a fundamental shift in our understanding of how paracetamol works. It positioned paracetamol not only as a central analgesic but also as a locally acting modulator of neuronal excitability.

Results

AM404 significantly reduced sodium current amplitude in isolated dorsal root ganglion (DRG) neurons in a dose-dependent manner. The greatest effect was observed on tetrodotoxin-resistant (TTX-R) sodium currents, which are characteristic of Nav1.8, a key player in chronic and inflammatory pain. AM404 had minimal effect on potassium and calcium currents, indicating a selective action on sodium channels.

In pharmacological profiling, AM404 showed the strongest inhibition of Nav1.7 and Nav1.8, both of which are highly expressed in nociceptive (pain-sensing) neurons. Other Nav subtypes, such as Nav1.5 (cardiac) and Nav1.6 (CNS), were minimally affected, suggesting a favorable safety profile by avoiding cardiac or CNS toxicity.

In formalin-induced inflammatory pain models, peripheral injection of AM404 significantly reduced both early (neurogenic) and late (inflammatory) phases of pain behaviors (licking, flinching). In the hot plate and tail flick thermal assays, AM404 increased latency to pain response, indicating effective thermal analgesia. Systemic or central (intrathecal) administration of AM404 had less prominent effects, highlighting that peripheral action is essential for its analgesic activity.

Computational docking predicted that AM404 binds to a hydrophobic fenestration site within the channel’s domain IV S6 segment, a region known to influence channel gating and drug binding.

Implications

This research challenges the traditional view of paracetamol as a centrally acting analgesic. It highlights that peripheral mechanisms, particularly in the context of inflammatory pain, are also crucial to its analgesic action. A key finding is the active pharmacological role of AM404, a metabolite of paracetamol, which is not just a metabolic byproduct but a potent modulator contributing to its pain-relieving effects. This adds to the recognition of the importance of drug metabolites in determining therapeutic efficacy. Moreover, the study strengthens the therapeutic relevance of targeting sodium channel subtype Na_V 1.7, positioning AM404 as a promising lead compound or molecular scaffold for the development of new, non-opioid analgesics.

Broader Impact: Beyond Paracetamol

This study opens exciting new avenues in the field of pain research. It triggers a re-evaluation of some metabolites that have been silent since their discovery and are also traditionally overlooked, but may possess key pharmacological actions, suggesting that other commonly used drugs could harbor unexplored therapeutic potential through their metabolites.

Additionally, the findings strengthen the scientific rationale for targeting peripheral sodium channels, particularly in managing chronic and inflammatory pain conditions. AM404, a paracetamol metabolite, exerts analgesic effects without causing sedation or respiratory depression, positioning it as a promising foundation for developing safer, non-addictive alternatives to opioids.

Conclusion

The discovery that AM404 blocks peripheral NaV channels redefines how we understand one of the worlds’s most commonly used analgesics. By uncovering this hidden peripheral pain pathway, researchers at the Hebrew University of Jerusalem have significantly advanced the field of analgesic pharmacology. This work not only deepens our molecular understanding of paracetamol but also opens up new possibilities for developing better pain medicines and emphasizing the vital role of peripheral targets in pain relief.

References

Y Maatuf, Y. Kushnir, A.Nemirovski, et al, The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels, Proc. Natl. Acad. Sci. U.S.A. 122 (23) e2413811122, https://doi.org/10.1073/pnas.2413811122

Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2008 Oct; 18(10):915-21. Doi: 10.1111/j.1460-9592.2008.02764.x. PMID: 18811827

Israeli study finds acetaminophen drug works by first blocking pain in nerves, The Times of Israel, https://www.timesofisrael.com/israeli-study-finds-acetaminophen-drug-works-by-first-blocking-pain-in-nerves/

New discovery: Tylenol stops pain at the nerves, before it hits the brain, ScienceDaily, https://www.sciencedaily.com/releases/2025/06/250610074247.htm#:~:text=Summary%3A,channels%20in%20pain%2Dsensing%20nerves.

Mallet C, Desmeules J, Pegahi R, Eschalier A. An Updated Review on the Metabolite (AM404)-Mediated Central Mechanism of Action of Paracetamol (Acetaminophen): Experimental Evidence and Potential Clinical Impact. J Pain Res. 2023 Mar 29;16:1081-1094. Doi: 10.2147/JPR.S393809. PMID: 37016715; PMCID: PMC10066900.

Sharma CV, Long JH, Shah S, Rahman J, Perrett D, Ayoub SS, Mehta V, First evidence of the conversion of paracetamol to AM404 in human cerebrospinal fluid. J Pain Res. 2017; 10:2703-2709 https://doi.org/10.2147/JPR.S143500

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Yutrepia (Treprostinil) Inhalation Powder developed on Liquidia’s PRINT technology Gets FDA Approval for Pulmonary Hypertension and Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD)

by with No Comment New Drug Approval

Written By: Dewanshee Ingale (B.Pharm)

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Source: Freepik.com

Yutrepia is an FDA-approved, inhaled dry-powder dosage form of treprostinil for treating pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). This approval provides patients with a novel, practical, and efficient therapy alternative, marking a substantial development in caring for these complicated conditions. Even though treprostinil has been in practice since 2002 in various dosage forms, recently treprostinil (Yutrepia) was approved by the FDA on May 23, 2025, especially as an inhalation powder formulation for the management and control of pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). Earlier, other inhaled forms, most remarkably an inhalation solution of treprostinil, were sanctioned in 2009 for the same indications (Tyvaso). The fundamental difference is that Yutrepia introduced the first FDA-approved dry powder inhalation dosage form of treprostinil, which proposes an entirely novel delivery technique and is based on Liquidia’s proprietary PRINT™ technology, which yields uniform, free-flowing particles intended for enhanced deep lung delivery via an easy-to-use, low-effort device requiring less inspiratory effort as compared to the prior nebulized solution.

Present data and background

Pulmonary arterial hypertension (PAH) and pulmonary hypertension with interstitial lung disease (PH-ILD) are progressive conditions that increase pulmonary artery pressure. This can be followed by right heart failure (associated with the right ventricle) and exercise intolerance. PAH was initially treated with four main mechanisms: endothelin-1, nitric oxide, prostacyclin, and bone morphogenetic protein/activin signaling, more recently. In recent times, physicians increasingly prescribe combination therapy, which is more effective for symptoms and outcomes compared to single treatment.

People with fibrotic lung diseases often develop a serious complication called pulmonary hypertension (PH-ILD), which makes their condition worse and increases the risk of death. Until recently, there were no approved treatments for this. Now, fast and effective treatment is important to manage the disease and improve outcomes. Initially the agents were unsuccessful and not safe, which revealed a lack of therapy and the need for effective and nontoxic treatment. The advent of inhaled treprostinil was innovative. The recent trials enhanced exercise capacity and reduced the severity of disease in patients with PH-ILD, which led to approval of the drug. As the traditional nebulized form was clumsy and time taking, led to decreased patient compliance. The dry inhalational powder of treprostinil was developed to provide a suitable, handy delivery system. The novel delivery technology is an enhancement in the therapy of PAH and PH-ILD, improving patient convenience and compliance in treatment.

Yutrepia: a novel approach

Treprostinil is a prostacyclin (PGI₂) analogue primarily used to treat Pulmonary Arterial Hypertension (PAH). It mimics the action of endogenous prostacyclin, a potent vasodilator and inhibitor of platelet aggregation. Treprostinil binds to IP receptors (prostacyclin receptors) on vascular smooth muscle cells. This activates adenylate cyclase, increasing cyclic AMP (cAMP) levels, which leads to smooth muscle relaxation and vasodilation, particularly in the pulmonary and systemic circulation. Treprostinil also inhibits platelet aggregation through the same cAMP-mediated pathway, which helps reduce the risk of thrombosis, a big alarm in PAH. Elevated cAMP levels also exert anti-proliferative effects on vascular smooth muscle cells, helping to prevent vascular remodelling, a characteristic of PAH progression. By mimicking prostacyclin, treprostinil can enhance endothelial cell function and reduce oxidative stress and inflammation in pulmonary arteries.

About Yutrepia and PRINT technology

Lungs_Graphic-new
Source:liquidia.com

Yutrepia is developed meticulously using Liquidia’s PRINT technology. The new drug is administered via a tiny, compact device that is lightweight and could be placed in the palms of hands. Development of Yutrepia efficiently utilizes Liquidia’s PRINT technology to formulate drug particles that are precise as well as uniform in size, shape, and composition in such a way that they can deliver more in the lungs when inhaled. The particle’s diameter is found to be 1.3 μm, which implies that the size of the particles is well controlled. The particles have a three-leaf clover shape, which facilitates their ability to effectively deliver drug.

Clinical trials and approval

The sanction of Yutrepia (Treprostinil) dry inhalational powder for pulmonary arterial hypertension(PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD) was supported on the pivotal, open-label, multicentre Phase 3 INSPIRE trial (ClinicalTrials.gov Identifier: NCT03399604). Furthermore, the ongoing ASCENT study (ClinicalTrials.gov Identifier: NCT06129240) is estimating the long-term safety criteria and acceptability of Yutrepia in patients with PH-ILD.

NCT03399604 an open-label, multicentre INPSPIRE trial phase III study was designed to assess the safety and tolerability of Yutrepia (dry-powder inhalational formulation of treprostinil) in adults with PAH. Overall 121 patients aged 18 years or above were registered, including the ones who transformed from nebulized treprostinil and prostacyclin naive patients which receive up to two non-prostacyclin oral therapies. Transition patients were started with Yutrepia at a dose that is equivalent to the prior nebulized dosing. The prostacyclin-naive patients were treated with 26.5 mcg four times daily, with dose modification in 26.5mcg in which growth can be allowed for both the groups.

The preliminary aims were to evaluate the occurrence of adverse events (AEs) and serious adverse (SAEs) throughout the entire study. Investigative efficacy parameters including changes in the 6-minute walk distances, NYHA (New York heart association), NT-proBNP levels (N-terminal pro-B-type natriuretic peptide) exposed that most patients stayed stable or enhanced over the one-year treatment time lapse. Moreover, quality of life scores enhanced, it was being observed that most of the patients preferred the Yutrepia inhaler over earlier used nebulized devices. In general, Yutrepia was discovered to be a suitable and very well-tolerated inhaled prostacyclin treatment therapy for PAH patients, assisting its use as a novel therapy option in this population.

The primary endpoints were the occurrence of AEs and SAEs. Throughout the one-year treatment period, 80% of the transition group and 96% of the prostacyclin-naive group modified to a dose of not less than 79.5 mcg four times daily, with at least one patient reaching 212 mcg daily four times. Majority of adverse effects were found to be mild to modest and steady prostacyclin therapy, comprising cough, headache, upper respiratory infection, dyspnoea, and throat irritation. Most of the patients remained stable or improved during the study.

Clinical trial NCT06129240, known as the ASCENT study, is an ongoing Phase 3, open-label, multicenter trial. It is designed to evaluate the long-term safety and tolerability of Yutrepia, a dry powder inhaled formulation of treprostinil, in patients with pulmonary hypertension (PH) and PH associated with interstitial lung disease (PH-ILD). The trial is still ongoing and recruiting participants.

Safety profile

Yutrepia (treprostinil) inhalation powder has established an appropriate safety and tolerability outline n clinical trials, remarkably in the pivotal phase III INSPIRE study. Approximately all the patients (99.2%) observed at least one adverse event (AE), while most of these being mild (47.9%) or moderate (28.1%) in seriousness. Harmful AEs were unusual (3.3%). In this clinical trials there were no serious adverse effects or mortality reported throughout the study.

The frequently reported adverse reactions <10% included not so serious side effects like cough, headache, and upper respiratory tract infections. The side effects were consistent with the known safety profile of the inhalational powder therapies and did not prevent patients from continuing treatment.

The patients who received higher percentage of prostacyclin-naive observed dose related AEs as compared the ones who were transitioned from the nebulized treprostinil (84.8% vs 72.7%). Although in general the incidence of moderate or severe AEs were quite controllable. Approximately 12.4% of patients did not continue the treatment due to AEs, among which 9.1% of these events were related to Yutrepia.

The medical monitor significantly did not observe any of the SAEs related to the Yutrepia in the trials. The maximum number of hospitalizations was because of unrelated causes like accidents, comorbidities, or any kind of viral infection, for example, COVID-19. There were no deaths reported during the study of the drug.

Impact and future viewpoint

The FDA approval of Yutrepia (treprostinil) provides with a new delivery system of inhalation dosage form by using dry inhalation powder for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated interstitial lung disease this led to enhanced exercise capability, suitability, and quality of life of patients who have limited treatment alternatives. The importance of constant research and invention in cardiopulmonary diseases were highlighted by the approval. Directing to extend therapeutic pathways and improve patient results.  

The upcoming research will discover the longstanding profits, ideal dosing approaches and the ability of Yutrepia to be utilized in wider patient populations. The present and upcoming studies, like the ASCENT trials, will moreover provide extra data on long-term safety and efficacy. With Yutrepia being more widely available, its distinctive dry powder dosage form and simple inhaler are probably to expand patient acceptance to prostacyclin therapy, leading to improved disease treatment for patients with PAH and PH-ILD.         

Refrences

YUTREPIA is an FDA-approved, inhaled dry-powder formulation of treprostinil indicated for the treatment of pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD)  https://liquidia.com/pipeline-and-products

FDA approval history for Yutrepia (treprostinil) used to treat Pulmonary Arterial Hypertension; Pulmonary Hypertension Associated with Interstitial lung disease (PH-ILD)https://www.drugs.com/history/Yutrepia.html

U.S. FDA Approves Liquidia’s YUTREPIA™ (treprostinil) Inhalation Powder for Patients with Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD)https://liquidia.com/news-releases/news-release-details/us-fda-approves-liquidias-Yutrepiatm-treprostinil-inhalation

FDA approval history for Tyvaso (treprostinil) used to treat Pulmonary Arterial Hypertension. Supplied by United Therapeutics Corporation https://www.drugs.com/history/tyvaso.html

Pulmonary Hypertension in Interstitial Lung Disease: Management Options to Move beyond Supportive Care https://pmc.ncbi.nlm.nih.gov/articles/PMC10200699/

Therapeutic Potential of Treprostinil Inhalation Powder for Patients with Pulmonary Arterial Hypertension: Evidence to Date https://pmc.ncbi.nlm.nih.gov/articles/PMC11162632/

INSPIRE: Safety and tolerability of inhaled Yutrepia (treprostinil) in pulmonary arterial hypertension (PAH) https://pmc.ncbi.nlm.nih.gov/articles/PMC9400582/

Liquidia Announces the Publication of Long-Term Clinical Data from Completed INSPIRE Study in the Journal Pulmonary Circulation https://liquidia.com/news-releases/news-release-details/liquidia-announces-publication-long-term-clinical-data-completed

FDA Approves Yutrepia (treprostinil) Inhalation Powder for Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD) https://www.drugs.com/newdrugs/fda-approves-Yutrepia-treprostinil-inhalation-powder-pulmonary-arterial-hypertension-pah-pulmonary-6529.html

Transitioning from Parenteral Treprostinil to LIQ861 in a Patient with PAH San Francisco, CA https://liquidia.com/publications

Hill, N.S. et al., INSPIRE: A Phase 3 Open-Label, Multicenter Study to Evaluate the Safety and Tolerability of LIQ861 in Pulmonary Arterial Hypertension (PAH) (Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil NCT03399604), The Journal of Heart and Lung Transplantation, Volume 38, Issue 4, S11

Hill NS, Feldman JP, Sahay S, INSPIRE study investigators. INSPIRE: Safety and tolerability of inhaled Y et al, utrepia (treprostinil) in pulmonary arterial hypertension (PAH). Pulm Circ. 2022 Jul 1;12(3):e12119. doi: 10.1002/pul2.12119. PMID: 36034402; PMCID: PMC9400582.

Roscigno R, Vaughn T, Anderson S, Wargin W, Hunt T, Hill NS. Pharmacokinetics and tolerability of LIQ861, a novel dry-powder formulation of treprostinil. Pulm Circ. 2020 Nov 19; 10(4):2045894020971509. Doi: 10.1177/2045894020971509. PMID: 33282202; PMCID: PMC7682229.

An Open-Label ProSpective MultiCENTer Study to Evaluate Safety and Tolerability of Dry Powder Inhaled Treprostinil in PH (ASCENT), ClinicalTrials.gov ID NCT06129240, https://clinicaltrials.gov/study/NCT06129240

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