lariocidin

Scientists Discover Lariocidin, a Potent Lasso Shaped Antibiotic in Garden Soil

by with No Comment Disease & DrugsResearch

Written By: Lavanya Chavhan B.Pharm

Reviewed by Vikas Londhe M.Pharm (Pharmacology)

lariocidin

In a remarkable twist of scientific serendipity, researchers have discovered a powerful new antibiotic in an unexpected place a soil sample taken from a technician’s garden. The compound, named lariocidin, belongs to a rare class of antibiotics known as lasso peptides, and has shown promising results in combating drug-resistant bacteria.

A Backyard Breakthrough

Researchers from McMaster University in Ontario, Canada, and the University of Illinois, Chicago, led by Gerry Wright, worked together to discover lariocidin a compound shown to be effective against drug-resistant bacteria.

The discovery came during routine screening of soil samples for potential antimicrobial agents. One particular sample, taken from a home garden, yielded a previously unknown strain of bacteria that produced a unique antimicrobial compound. Upon further study, scientists isolated and characterized lariocidin, a small, intricately folded peptide that adopts a lasso-like structure.

Lasso peptides are named for their distinctive topology — a loop formed by the peptide backbone is threaded by its tail and locked into place, forming a mechanically constrained molecule. This unique structure often contributes to their stability and resistance to degradation, making them particularly appealing as drug candidates.

Lasso Peptide

A lasso peptide is a type of ribosomally synthesized and post-translationally modified peptide (RiPP) that has a unique and highly stable three-dimensional structure, resembling a lasso or slipknot.

Lasso peptides are characterized by A macrolactam ring (a circular peptide structure) at the N-terminus. A tail segment that threads through this ring during synthesis. The tail is “locked” in place by bulky amino acid residues or disulfide bonds, preventing it from slipping back out much like a rope threaded through a loop and pulled tight, hence the name lasso.

This structure is thermodynamically stable and resistant to heat, enzymatic degradation, and extreme pH conditions.

Targeting the Ribosome: A Novel Mechanism

What sets lariocidin apart is its mechanism of action. Unlike many antibiotics that attack bacterial cell walls or DNA replication, lariocidin targets bacterial ribosomes the machinery responsible for protein synthesis. It binds tightly to the ribosome and disrupts translation, halting the production of essential proteins needed for bacterial survival and replication.

Structural studies revealed that lariocidin latches onto a previously underexplored site on the ribosome, a feature that likely contributes to its efficacy against multi-drug resistant strains. This includes pathogens such as Staphylococcus aureus, Enterococcus faecium, and certain strains of Pseudomonas aeruginosa, which have become increasingly difficult to treat with conventional antibiotics.

A Weapon against Superbugs

The rise of antibiotic resistance is a global public health crisis. Each year, antimicrobial-resistant infections claim hundreds of thousands of lives worldwide. The emergence of lariocidin offers a glimmer of hope, especially since it belongs to a relatively untapped class of natural antibiotics with novel mechanisms of action.

Early laboratory studies have demonstrated that lariocidin is not only potent but also exhibits low toxicity to human cells, an essential step toward potential clinical development. Researchers are now working to synthesize analogs of lariocidin, optimize its pharmacokinetics, and assess its efficacy in animal models of infection.

Current status of Lariocidin

In preclinical testing, lariocidin showed strong antibacterial effects without exhibiting toxicity to human cells. In mouse models infected with A. baumannii, the antibiotic significantly lowered bacterial levels and improved survival outcomes.

At present, scientists are working to optimize lariocidin’s potency and are developing scalable production methods to support future clinical use. Although the results so far are encouraging, additional research and clinical trials are essential to confirm its safety and effectiveness in humans.

Nature Still Has Secrets to Reveal

The story of lariocidin is a potent reminder that nature, even in the soil of a backyard garden remains a vast and largely unexplored resource for life-saving compounds. With rising antibiotic resistance threatening global health, the discovery underscores the importance of continued investment in natural product research and microbial biodiversity.

If further studies validate its safety and effectiveness, lariocidin could represent the first in a new class of antibiotics, one that might help turn the tide against resistant bacterial infections.

References

1.Jangra, M., Travin, D.Y., Aleksandrova, E.V. et al.A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome. Nature(2025). https://doi.org/10.1038/s41586-025-08723-7

2. New lasso-shaped antibiotic kills drug-resistant bacteria, Nature Podcast, Nature, 26 March 2025

3. Julian D. Hegemann, Marcel Zimmermann, Xiulan Xie et al, Lasso Peptides: An Intriguing Class of Bacterial Natural Products, Accounts of Chemical ResearchVol 48, Issue 7 2015

4. Cheng Cheng, Zi-Chun Hua et al, Lasso Peptides: Heterologous Production and Potential Medical Application, Front. Bioeng. Biotechnol. Volume 8 – 2020 https://doi.org/10.3389/fbioe.2020.571165

5. Digging in the dirt: Scientists discover a new antibiotic compound from an old source, University of Minnesota, 31 March 2025

6.Molecule Discovered In Backyard Soil Can Fight Drug Resistant Bacteria, Technology Networks Immunology and Microbiology, 28 March 2025

 

avian influenza

From Poultry to People: The Rising Risk of Avian Influenza (Bird Flu)

by with No Comment Health Tidings

Written By Pragati Ekamalli B.Pharm

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

avian influenza

Introduction

Bird flu, also known as avian influenza, is a sickness caused by Type A viruses. The first known case of a serious form of bird flu was reported in 1959, and in 1996, a specific strain called H5N1 was found in China. These viruses can infect farm animals like chickens and turkeys and can spread among wild aquatic birds like ducks and geese around the world. Some bird flu viruses can also affect other animals. Normally, humans do not get bird flu, but there have been rare cases where people became infected. This can happen when someone has close contact with sick birds or animals, especially if they touch their face after touching an infected animal or object. The virus can be found in the body fluids of infected animals.

History of avian influenza

In 1878, a vet in northern Italy saw many chickens dying. People didn’t understand viruses well then, so they named the sickness “fowl plague.” At first, it was mixed up with “fowl cholera,” which is caused by bacteria.

By 1901, scientists found out that “fowl plague” were caused by a virus. They figured this out because it could go through a filter, showing it was much smaller than bacteria. Later, technology showed that the virus was a type of H1N1 that affects birds.

In April 1981, at a meeting in First International Symposium on Avian Influenza  at Maryland, researchers decided to stop using the name fowl plague and called it highly pathogenic avian influenza (HPAI) instead.

Types of Avian Influenza

Low Pathogenic Avian Influenza (LPAI):   Low pathogenic avian influenza (LPAI) viruses typically cause mild or no symptoms in poultry and wild birds. However, in poultry, some LPAI strains can mutate into highly pathogenic forms.

Highly pathogenic avian influenza (HPAI): Highly harmful bird flu viruses, especially types A (H5) and A (H7), can make chickens very sick, often killing them within 48 hours. Most bird flu strains are less harmful, but some wild birds and ducks can carry the dangerous virus without showing signs of illness and spread it when they migrate. Some types can also kill wild birds, helping the virus spread around the world and putting both animals and people at risk.


Situation of Avian Influenza in USA

The first big outbreak of bird flu in the U.S. happened in Pennsylvania from 1983 to 1984, caused by the H5N2 strain, leading to the killing of over 17 million birds. In 2002-2003, a less severe H7N2 outbreak in Virginia led to more safety measures. The worst outbreak was in 2014-2015, when H5N2 and H5N8 strains affected the Midwest, resulting in the loss of over 50 million birds, especially in Iowa and Minnesota. Smaller outbreaks happened from 2016 to 2020, mostly affecting small farms and wild birds, highlighting the need for careful monitoring.

Currently, the U.S. is seeing cases of bird flu linked to the H5N1 strain, which has been spreading worldwide since 2021. This virus reached North America that same year, infecting many wild birds and farmed poultry in several states. Since 2022, many wild birds have tested positive for H5N1, and millions of farmed birds have been killed to stop the virus from spreading. Human cases have been rare, but there is still concern about possible transmission to people. A human case was confirmed in 2022 in Colorado involving a poultry worker who had mild symptoms and fully recovered.

In March 2024, H5N1 was found in U.S. dairy cows for the first time. The first infected herds were in Texas and Kansas, with more cases reported in over ten states. The virus was also found in raw milk and nasal swabs, leading to further investigations. This was the first time H5N1 affected large mammals in the U.S. In April 2024, a human case linked to dairy cattle was confirmed in Texas. The person, a dairy worker, had conjunctivitis and fully recovered.

While the overall risk to human health remains low, the continued spread of H5N1 among birds and now mammals represents a serious threat to the agricultural sector. The potential for viral mutations that could make human transmission more efficient is a key concern for health officials.

Current Human Avian Influenza Cases

As of April 2025, there have been several notable developments in human cases of avian influenza (bird flu), particularly involving the H5N1 subtype.

Mexico’s First Human Fatality: A 3-year-old girl from Coahuila, Mexico, tragically died from H5N1 infection, marking the country’s first confirmed human case. Investigations are ongoing to determine the source of infection, with tests on 38 close contacts returning negative results, indicating no immediate human-to-human transmission.

United States Occupational Exposures: In 2024, the U.S. reported 46 human H5N1 cases across six states, primarily among poultry and dairy workers. Most cases were mild, with no critical illnesses or fatalities. Notably, personal protective equipment (PPE) usage among these workers was found to be suboptimal.

Retrospective Worldwide fatality of H5N1

Indonesia: Indonesia has reported the highest number of human fatalities from avian influenza (H5N1) globally, with over 160 deaths since 2003. Most cases resulted from close contact with infected poultry.

Egypt: Egypt has had the highest number of H5N1 cases in the Middle East and Africa, with over 120 confirmed cases and more than 35 fatalities, primarily affecting rural areas with backyard poultry.

Vietnam: Vietnam has experienced 63 deaths from H5N1 since 2003. Despite aggressive control measures, sporadic outbreaks and fatalities have continued due to poultry exposure.

Cambodia: Cambodia has reported over 30 human cases of H5N1, with a high fatality rate, most of the infected individuals died, often due to delayed treatment in rural areas.

China: China has reported fewer human deaths compared to other countries, but still significant, with over 50 fatalities from H5N1 and other avian influenza strains like H7N9, which emerged in 2013.

Cumulative Global Cases: Since 2003, over 950 human H5N1 infections have been reported across 24 countries, with a case fatality rate of approximately 49%.

Public Health Response

Vaccine Development: In response to the growing threat, the U.S. Department of Health and Human Services has allocated $590 million to Moderna for the development of mRNA-based vaccines targeting multiple bird flu subtypes. ​

​Arcturus Therapeutics Holdings Inc. has received FDA clearance to initiate clinical trials for its H5N1 pandemic influenza vaccine candidate, ARCT-2304, also known as LUNAR-H5N1. This self-amplifying mRNA (sa-mRNA) vaccine utilizes Arcturus’ proprietary STARR® platform and LUNAR® delivery technology.

Surveillance Efforts: The Centers for Disease Control and Prevention (CDC) is actively monitoring the situation, utilizing flu surveillance systems to detect H5 bird flu activity in humans and working with states to monitor individuals with animal exposures, subsequently, in April 2025, the FDA granted Fast Track designation to ARCT-2304, aiming to expedite its development and review process.

Conclusion

Bird flu, especially the H5N1 type, has changed from a small problem in birds to a serious worry for both animals and people. More cases are being seen in wild birds, farm animals, and even cows. The virus is showing it can jump from one species to another. While there are not many human cases, the chance that it could change and spread more widely is a big concern. This shows we need to keep a close watch, respond quickly, and speed up vaccine development. As the situation develops, countries need to work together to reduce the risk of a future outbreak and keep people healthy and food supplies safe.

Introduction

Bird flu, also known as avian influenza, is a sickness caused by Type A viruses. The first known case of a serious form of bird flu was reported in 1959, and in 1996, a specific strain called H5N1 was found in China. These viruses can infect farm animals like chickens and turkeys and can spread among wild aquatic birds like ducks and geese around the world. Some bird flu viruses can also affect other animals. Normally, humans do not get bird flu, but there have been rare cases where people became infected. This can happen when someone has close contact with sick birds or animals, especially if they touch their face after touching an infected animal or object. The virus can be found in the body fluids of infected animals.

History of avian influenza

In 1878, a vet in northern Italy saw many chickens dying. People didn’t understand viruses well then, so they named the sickness “fowl plague.” At first, it was mixed up with “fowl cholera,” which is caused by bacteria.

By 1901, scientists found out that “fowl plague” were caused by a virus. They figured this out because it could go through a filter, showing it was much smaller than bacteria. Later, technology showed that the virus was a type of H1N1 that affects birds.

In April 1981, at a meeting in First International Symposium on Avian Influenza  at Maryland, researchers decided to stop using the name fowl plague and called it highly pathogenic avian influenza (HPAI) instead.

Types of Avian Influenza

Low Pathogenic Avian Influenza (LPAI):   Low pathogenic avian influenza (LPAI) viruses typically cause mild or no symptoms in poultry and wild birds. However, in poultry, some LPAI strains can mutate into highly pathogenic forms.

Highly pathogenic avian influenza (HPAI): Highly harmful bird flu viruses, especially types A (H5) and A (H7), can make chickens very sick, often killing them within 48 hours. Most bird flu strains are less harmful, but some wild birds and ducks can carry the dangerous virus without showing signs of illness and spread it when they migrate. Some types can also kill wild birds, helping the virus spread around the world and putting both animals and people at risk.

Situation of Avian Influenza in USA

The first big outbreak of bird flu in the U.S. happened in Pennsylvania from 1983 to 1984, caused by the H5N2 strain, leading to the killing of over 17 million birds. In 2002-2003, a less severe H7N2 outbreak in Virginia led to more safety measures. The worst outbreak was in 2014-2015, when H5N2 and H5N8 strains affected the Midwest, resulting in the loss of over 50 million birds, especially in Iowa and Minnesota. Smaller outbreaks happened from 2016 to 2020, mostly affecting small farms and wild birds, highlighting the need for careful monitoring.

Currently, the U.S. is seeing cases of bird flu linked to the H5N1 strain, which has been spreading worldwide since 2021. This virus reached North America that same year, infecting many wild birds and farmed poultry in several states. Since 2022, many wild birds have tested positive for H5N1, and millions of farmed birds have been killed to stop the virus from spreading. Human cases have been rare, but there is still concern about possible transmission to people. A human case was confirmed in 2022 in Colorado involving a poultry worker who had mild symptoms and fully recovered.

In March 2024, H5N1 was found in U.S. dairy cows for the first time. The first infected herds were in Texas and Kansas, with more cases reported in over ten states. The virus was also found in raw milk and nasal swabs, leading to further investigations. This was the first time H5N1 affected large mammals in the U.S. In April 2024, a human case linked to dairy cattle was confirmed in Texas. The person, a dairy worker, had conjunctivitis and fully recovered.

While the overall risk to human health remains low, the continued spread of H5N1 among birds and now mammals represents a serious threat to the agricultural sector. The potential for viral mutations that could make human transmission more efficient is a key concern for health officials.

Current Human Avian Influenza Cases

As of April 2025, there have been several notable developments in human cases of avian influenza (bird flu), particularly involving the H5N1 subtype.

Mexico’s First Human Fatality: A 3-year-old girl from Coahuila, Mexico, tragically died from H5N1 infection, marking the country’s first confirmed human case. Investigations are ongoing to determine the source of infection, with tests on 38 close contacts returning negative results, indicating no immediate human-to-human transmission.

United States Occupational Exposures: In 2024, the U.S. reported 46 human H5N1 cases across six states, primarily among poultry and dairy workers. Most cases were mild, with no critical illnesses or fatalities. Notably, personal protective equipment (PPE) usage among these workers was found to be suboptimal.

Retrospective Worldwide fatality of H5N1

Indonesia: Indonesia has reported the highest number of human fatalities from avian influenza (H5N1) globally, with over 160 deaths since 2003. Most cases resulted from close contact with infected poultry.

Egypt: Egypt has had the highest number of H5N1 cases in the Middle East and Africa, with over 120 confirmed cases and more than 35 fatalities, primarily affecting rural areas with backyard poultry.

Vietnam: Vietnam has experienced 63 deaths from H5N1 since 2003. Despite aggressive control measures, sporadic outbreaks and fatalities have continued due to poultry exposure.

Cambodia: Cambodia has reported over 30 human cases of H5N1, with a high fatality rate, most of the infected individuals died, often due to delayed treatment in rural areas.

China: China has reported fewer human deaths compared to other countries, but still significant, with over 50 fatalities from H5N1 and other avian influenza strains like H7N9, which emerged in 2013.

Cumulative Global Cases: Since 2003, over 950 human H5N1 infections have been reported across 24 countries, with a case fatality rate of approximately 49%.

Public Health Response

Vaccine Development: In response to the growing threat, the U.S. Department of Health and Human Services has allocated $590 million to Moderna for the development of mRNA-based vaccines targeting multiple bird flu subtypes. ​

​Arcturus Therapeutics Holdings Inc. has received FDA clearance to initiate clinical trials for its H5N1 pandemic influenza vaccine candidate, ARCT-2304, also known as LUNAR-H5N1. This self-amplifying mRNA (sa-mRNA) vaccine utilizes Arcturus’ proprietary STARR® platform and LUNAR® delivery technology.

Surveillance Efforts: The Centers for Disease Control and Prevention (CDC) is actively monitoring the situation, utilizing flu surveillance systems to detect H5 bird flu activity in humans and working with states to monitor individuals with animal exposures, subsequently, in April 2025, the FDA granted Fast Track designation to ARCT-2304, aiming to expedite its development and review process.

Conclusion

Bird flu, especially the H5N1 type, has changed from a small problem in birds to a serious worry for both animals and people. More cases are being seen in wild birds, farm animals, and even cows. The virus is showing it can jump from one species to another. While there are not many human cases, the chance that it could change and spread more widely is a big concern. This shows we need to keep a close watch, respond quickly, and speed up vaccine development. As the situation develops, countries need to work together to reduce the risk of a future outbreak and keep people healthy and food supplies safe.

References

1.Tripathi AK, Sendor AB, Sapra A. Avian Influenza. [Updated 2025 Feb 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from:https://www.ncbi.nlm.nih.gov/books/NBK553072/

2. Avian Influenza, World Organization for Animal Health, available from https://www.woah.org/en/disease/avian-influenza/

3. H5 Bird Flu: Current Situation, US centres for disease control and prevention, 11 April 2025, available from https://www.cdc.gov/bird-flu/situation-summary/index.html

 4. Confirmations of Highly Pathogenic Avian Influenza in Commercial and Backyard Flocks, Animal and Plant Health Inspection Service, U.S. Department Of Agriculture

5. Lycett SJ, Duchatel F, Digard P. A Brief History of Bird Flu. Philos Trans R Soc Lond B Biol Sci. 2019 Jun 24; 374(1775):20180257. Doi: 10.1098/rstb.2018.0257. PMID: 31056053; PMCID: PMC6553608.

 6. 2020-2024 Highlights in the History of Avian Influenza (Bird Flu) Timeline, US centres for disease control and prevention, 30 April 2024, available from https://www.cdc.gov/bird-flu/avian-timeline/2020s.html

7. What Are the Earliest Known Origins of Bird Flu? Available from https://www.history.com/articles/bird-flu-origins-humans-pandemic

8. Past Reported Global Human Cases with Highly Pathogenic Avian Influenza A (H5N1) (HPAI H5N1) by Country, 1997-2025, avian Influenza (Bird Flu), available from https://www.cdc.gov/bird-flu/php/avian-flu-summary/chart-epi-curve-ah5n1.html

9. Avian Influenza Weekly Update # 993: 11 April 2025, World Health Organization, available from https://www.who.int/westernpacific/publications/m/item/avian-influenza-weekly-update—993–11-april-2025

 10. Global Avian Influenza Viruses with Zoonotic Potential situation update, Animal Health, Food and Agriculture organization of United Nations, available from https://www.fao.org/animal-health/situation-updates/global-aiv-with-zoonotic-potential/en

11. Avian Influenza (H5N1) Vaccines: What’s the Status? American Society of Microbiology, 04 March 2025, available from https://asm.org/articles/2025/march/avian-influenza-h5n1-vaccines-what-status

 12. US awards Moderna $590 million for bird flu vaccine development, Reuters, January 18 2025, available from https://www.reuters.com/business/healthcare-pharmaceuticals/us-awards-moderna-590-million-bird-flu-vaccine-development-2025-01-17/

 13. Arcturus Therapeutics Receives U.S. FDA Fast Track Designation for the STARR® mRNA Vaccine Candidate ARCT-2304 for Pandemic Influenza A Virus H5N1, Arcturus Therapeutics, 10 April 2025, available from https://ir.arcturusrx.com/node/13116/pdf

odactra (2)

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

by with No Comment Disease & DrugsNew Drug Approval

Written By Lavanya Chavhan B.Pharm

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

odactra (2)

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

  1. 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.

Qfitlia_optimized_2000

FDA Approves Qfitlia: First siRNA Therapy for Haemophilia Prophylaxis

by with No Comment Disease & DrugsNew Drug Approval

Written by Aishwarya Shinde (B.Pharm)

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

Qfitlia_optimized_2000

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.

 

VHL Welireg

EMA Approves Welireg (Belzutifan): A Breakthrough for VHL-Associated Tumors and Advanced Kidney Cancer

by with No Comment Disease & DrugsNew Drug Approval

Written By Yogita Bhadane, B.Pharm

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

VHL Welireg

Introduction
Welireg (belzutifan), a significant advancement, has been approved by the European Medicines Agency (EMA) as the first clinically approved pharmaceutical therapy for tumors associated with von Hippel-Lindau (VHL) disease and for adults with advanced renal cell carcinoma (RCC) who have already received treatment. As a new targeted therapy for unmet medical needs, this approval holds promise for clinicians treating these difficult conditions.

Understanding VHL Disease and RCC

Von Hippel-Lindau disease (VHL) is a rare genetic disorder that predisposes people to develop tumors and cysts in the kidneys, pancreas, and central nervous system, with kidney cancer being the most common type. Renal cell carcinoma occurs in an abnormal 70% of individuals with VHL syndrome. These tumors are caused by mutations in the VHL gene, which affects how the gene regulates the breakdown of proteins called hypoxia-inducible factor (HIF), which are sensitive to tissue oxygen levels. Tumor formation results from aberrant HIF activation brought on by VHL mutation. Conventional management techniques involved frequent surgical procedures and constant monitoring, which increased risks and lowered patient living standards. Immunocheckpoint inhibitors and anti-angiogenic therapies are used in the treatment of advanced renal cell carcinoma; however, post-progression care options are still scarce.

Hemangioblastomas

These non-cancerous growths mostly appear in the retina, spinal cord, and brain tissue. Brain hemangioblastoma patients are more likely to experience symptoms like headaches, vision issues, and neurological impairments.

Renal Cell Carcinomas (RCC)

The risk of kidney cancer, primarily clear cell renal carcinoma, is increased in people with VHL disease. In addition to renal impairment, these disorders often manifest bilaterally and cause hematuria and dysuria. Some examples show that (heterogeneous) petrocalcic deposits give rise to saddle-shaped inclusions.

 Pheochromocytomas:

High blood pressure, headaches, sweating, and palpitations are some of the symptoms caused by these tumors growing on the adrenal gland, which strictly adhere to EPI while binding to norepinephrine. Although phenochromocytomas usually appear as benign tumors, if left untreated, they have the potential to become fatal.

 Pancreatic Cysts and Tumors:

Patients with VHL may develop pancreatic cysts. Although the majority of them are benign, tiny molecules have the potential to develop into pancreatic neuroendocrine tumors, which may release hormones that result in various symptoms.

 Endolymphatic Sac Tumors (ELSTs):

Almost all of these are tumors that are located in the patient’s ear near the inner ear. Tinnitus, instability, and hearing loss are possible symptoms for those who have this condition. Chemotherapy or even stereotactic radiation may be used to treat general growth and low-grade ELSTs.

 Retinal Angiomas:

Hemangioblastomas, also known as retinal angiomas, are tumors of the blood vessels that frequently develop in the membrane of the eye and can cause partial blindness. Hemangioblastomas appear when they cause bleeding or retinal detachment, or when they are discovered during an eye exam.

Welireg’s Mechanism:

Angiogenesis (the formation of blood vessels), erythropoiesis (the production of red blood cells), and tumor growth are all regulated by HIF-2α.
The Von Hippel-Lindau (VHL) protein breaks down HIF-2α under normal oxygen conditions.
HIF-2α builds up in tumors that lack VHL, such as clear cell renal cell carcinoma and von Hippel-Lindau disease-associated tumors, which causes the tumor to grow out of control.

 Blocking HIF-2α Dimerization with HIF-1β:

By binding specifically to HIF-2α, belzutifan stops it from interacting with HIF-1β, which is a prerequisite for HIF-2α to activate target genes.
VEGF (vascular endothelial growth factor), PDGF (platelet-derived growth factor), and EPO (erythropoietin) are among the genes involved in tumor survival whose transcription is inhibited by this.

 Anti-Tumor Effects:

Welireg is effective in cancers caused by HIF-2α overactivity, especially VHL-associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, and pancreatic neuroendocrine tumors, because it inhibits HIF-2α signaling, which in turn reduces tumor growth, angiogenesis, and erythropoiesis.

An important tumor growth pathway is disrupted by the oral hypoxia-inducible factor 2 alpha (HIF-2α) inhibitor belzutifan. HIF-2α builds up in low oxygen environments, activating genes that support angiogenesis and cell division. Welireg deprives tumors of these signals by blocking HIF-2α, which slows growth and causes shrinkage. This mechanism is revolutionary because it provides a precision medicine approach that is specific to the molecular drivers of RCC and VHL.

Clinical Trial Efficacy

VHL-Associated Tumors: Belzutifan is being evaluated in patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) in the Phase 2 open-label clinical trial NCT03401788 (Study 004). 61 adults with at least one detectable RCC tumor and a germline VHL alteration were enrolled. Additionally, patients may have pancreatic neuroendocrine tumors (pNETs) or CNS hemangioblastomas. Prior use of HIF-2α inhibitors, systemic therapy, surgical necessity, and metastatic disease were excluded. Until toxicity or progression, participants were given 120 mg of belzutifan every day. Overall response rate (ORR), the main outcome, was 49% in RCC, 63% in CNS hemangioblastomas, and 83% in pNETs. With more than half of respondents continuing to respond for more than 12 months, the median response duration was not reached.

Advanced RCC: Belzutifan, a hypoxia-inducible factor 2α (HIF-2α) inhibitor, is being evaluated in patients with advanced solid tumors as part of the LITESPARK-001 trial (NCT02974738), a phase 1 clinical study. 55 patients with advanced ccRCC who had previously received treatment were given 120 mg of belzutifan orally once daily as part of this cohort. The objective response rate (ORR), which included one complete response and thirteen partial responses, was 25% following a median follow-up of more than three years. The median progression-free survival (PFS) was 14.5 months, and the disease control rate (DCR) was 80%. Anaemia (24% grade 3) and hypoxia (13% grade 3) were the most common treatment-related adverse events; no grade 4 or grade 5 treatment-related adverse events were noted. These findings show that belzutifan has a manageable safety profile and long-lasting antitumor activity in patients with ccRCC who have received extensive pre-treatment.

Glioblastoma (GBM) Cohort: A cohort of 25 patients with recurrent IDH wild-type glioblastoma after radiation therapy and temozolomide was also included in the trial. Belzutifan 120 mg was given orally to the patients twice a day. There were no objective responses after a median follow-up of 1.9 months; the median PFS was 1.4 months, and the clinical benefit rate was 8%. Every patient had at least one adverse event, and 60% of them had grade 3-5 events. Anaemia (64%), exhaustion (52%), headache (32%), and muscle weakness (32%), were the most frequent adverse events. There were no deaths brought on by the treatment. These results imply that in this GBM cohort, belzutifan did not exhibit antitumor activity.
Belzutifan’s potential for treating advanced ccRCC is generally highlighted by the LITESPARK-001 trial, but its effectiveness in treating GBM has not yet been established.

Safety and Tolerability

Administration of Welireg during pregnancy can cause embryo-fetal harm. It was highly recommended to confirm the pregnancy status before initiating Welireg.

Anaemia (71%), Hypoxia (48%), and nausea (31%), which are usually mild to moderate, are common side effects. It is advised to regularly check oxygen and hemoglobin levels. When compared to intravenous treatments, the ease of oral administration (120 mg once daily) improves patient adherence.

EMA Approval and Patient Impact

With the EMA’s support, access is made possible throughout the EU, changing the way that care is provided. Welireg preserves organ function and quality of life for VHL patients by lowering the need for invasive surgeries. It closes a crucial gap left by post-standard therapies for advanced RCC. “Belzutifan represents a paradigm shift, offering a non-invasive option with meaningful clinical benefits,” says oncologist Dr. Maria Ruiz.

 Future Directions

Belzutifan is being studied for combination treatments and other cancers driven by HIF-2α. Its success highlights how hypoxia pathways can be targeted in oncology.

Conclusion
The approval of Welireg, which addresses long-standing issues in the management of VHL and RCC, is a victory for precision medicine. Belzutifan sets a new standard by focusing on innovation in rare and complex cancers and coordinating treatment with disease biology. This milestone opens the door for future advancements in targeted therapies in addition to providing immediate clinical benefits.

References:

1. First medicine to treat rare genetic disorder causing cysts and tumours, European Medicine Agency, 13 December 2024

2. WELIREG® (belzutifan) Receives First European Commission Approval for Two Indications, Merck, 18 February 2025

3. Kim E, Zschiedrich S. Renal Cell Carcinoma in von Hippel-Lindau Disease-From Tumor Genetics to Novel Therapeutic Strategies. Front Pediatr. 2018 Feb 9;6:16. doi: 10.3389/fped.2018.00016. PMID: 29479523; PMCID: PMC5811471.

4. Ashouri K, Mohseni S, Tourtelot J, Sharma P, Spiess PE. Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma. J Kidney Cancer VHL. 2015 Sep 25; 2(4):163-173. Doi: 10.15586/jkcvhl.2015.41. PMID: 28326271; PMCID: PMC5345519.

5. Eric Jonasch, Frede Donskov, Othon Iliopoulos, Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease, n engl j med 385;22, November 25, 2021.

6. Hu, J., Tan, P., Ishihara, M. et al.Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma. Sig Transduct Target Ther8, 155 (2023). https://doi.org/10.1038/s41392-023-01362-2

7. Roy E. Strowd et al., Phase 1 LITESPARK-001 study of belzutifan in advanced solid tumors: Results of the glioblastoma cohort. JCO 42, 2054-2054(2024). DOI:10.1200/JCO.2024.42.16_suppl.2054

epv

Earth Day Spotlight: How Ecopharmacovigilance Protects the Planet from Pharmaceutical Pollution

by with No Comment Disease & DrugsResearch

Medically Written and Reviewed by Vikas Londhe M.Pharm (Pharmacology)

epv

As we honour Earth Day and reflect on our collective duty to protect the environment, a lesser-known but critical issue deserves the spotlight: Ecopharmacovigilance. In the era where much attention is given to industrial emissions and plastic waste, Very few people are aware of the silent threat created by pharmaceuticals entering the ecosystems. That’s where ecopharmacovigilance comes in

What is Ecopharmacovigilance?

Pharmaceuticals are meant to be developed for the consumption of humans; however, once humans consume pharmaceuticals, the by-products or remains are excreted into the environment in different ways, and once they enter the environment, they start polluting nature and harming the aquatic animals and other species, including soil and trees. Hence, where pharmacovigilance is the detection and understanding of the side effects of pharmaceuticals on humans, ecopharmacovigilance refers to the science and activities related to the detection, evaluation, understanding, and prevention of adverse effects or other problems related to the presence of pharmaceuticals in the environment. On a broader scale, it is monitoring the presence of pharmaceuticals in the environment, assessing the impact on non-target organisms, understanding it thoroughly, and developing the preventive strategies in a way that any harm to nature due to the presence of pharmaceuticals in the environment should be avoided timely and appropriately.

According to the World Health Organization, treated sewage water, surface water, drinking water, groundwater, sediment, soil, and biota contain hundreds of pharmaceuticals. Increasing use of drugs worldwide, and some of them are resistant to degradation, are the main reasons behind their presence in harmful quantities in nature. The most notable pathways of these pharmaceuticals are excretion of used drugs, drug manufacturing, industrial and home wastewater, aquaculture, manure application, landfills, and incineration.

Why Should We Care?

While pharmaceuticals are essential for human and animal health, their unintended environmental footprint is becoming increasingly evident. Studies have shown:

Increasing Antibiotic Resistance: Antibiotic resistance, or antimicrobial resistance (AMR), poses a global threat due to the irrational use of antibiotics; however, the presence of antibiotics in the environment makes the condition worse, as the exposed antibiotics in open environments make bacterial infections hard to treat. AMR caused an estimated 1.27 million deaths globally in 2019.

Effect on aquatic life: As most of the drugs end up in aquatic bodies like rivers, streams, ponds, and oceans through pathways mentioned above, they are not designed to be there or show a positive effect on wildlife present in waters. They show a negative effect on aquatic animals like fish and affect their ability to reproduce, cause behavior changes, or have direct toxic effects. Hormonal drugs, like estrogens from contraceptives, are supposed to be causing these types of effects. Some reports show that male fish were feminized by ethinyl estradiol and frogs were killed by contraceptive tablets. Psychiatric and cardiovascular drugs have been linked to altered behavior and physiological changes in aquatic animals. Some reports related to it show that aggression is caused in lobsters due to antidepressants and spawning in shellfish by fluoxetine.

Current Status of Ecopharmacovigilance

Regulatory Recognition

The OECD report Pharmaceutical Residues in Freshwater: Hazards and Policy Responses highlights the growing concern over pharmaceutical contamination in global freshwater systems due to human and veterinary use, manufacturing, and improper disposal.

The report emphasizes the need for a life cycle, multi-sectoral approach involving source-directed, use-oriented, and end-of-pipe solutions. This includes better monitoring, green pharmaceutical design, responsible prescription and use, proper disposal systems, and advanced wastewater treatment.

International Cooperation Needed: The report also emphasizes the importance of data sharing, international standards, public education, and financial strategies to implement sustainable pharmaceutical pollution control.

EMA and FDA integrated environmental risk assessments (ERAs) into the drug approval process

The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have taken significant steps to integrate Environmental Risk Assessments (ERAs) into the drug approval process, marking a growing recognition of the environmental impact of pharmaceuticals.

Environmental risk assessments evaluate the potential environmental impact of a pharmaceutical substance once it enters ecosystems, typically through human excretion, improper disposal, or manufacturing waste. These assessments analyze factors such as persistence in the environment, bioaccumulation in wildlife, toxicity to aquatic and terrestrial organisms, and potential for environmental transformation into harmful by-products.

Since 2005, the EMA has required ERAs for all new marketing authorization applications in the EU.

The FDA has also implemented environmental reviews under the National Environmental Policy Act (NEPA). For human drugs, applicants typically submit an Environmental Assessment (EA) or a claim for categorical exclusion, depending on the drug’s characteristics. The FDA assesses factors such as expected introduction into the environment, manufacturing and disposal practices, and the cumulative impact of widespread use.

As awareness of pharmaceutical pollution grows, both agencies are expected to tighten guidelines, enhance transparency, and collaborate internationally on standardized ERA methodologies. This reflects a shift toward sustainable drug development that balances therapeutic benefit with environmental responsibility.

What Can You Do?

On Earth Day and every day individuals can play a role in supporting ecopharmacovigilance:

Proper Medication Disposal

Don’t flush unused meds in the toilet or sink.

Use take-back programs: Many pharmacies and communities have medication disposal programs.

If no programs are available, follow the FDA’s or local authority’s guidelines for trash disposal (e.g., mix with unpalatable substances like coffee grounds or cat litter, then seal in a bag).

Buy Only What You Need

Avoid stockpiling medications. It reduces waste and environmental load from expired drugs.

Use Medications Responsibly

Follow prescriptions exactly—using less or more than necessary not only harms health but also leads to excess drugs in the environment.

Spread Awareness

Talk to friends and family about why proper disposal matters

Share posts or articles about EPV and pharmaceutical pollution.

Ask Your Pharmacist

If unsure about disposal or environmentally safer alternatives, ask to your pharmacist. Pharmacist is the healthcare provider who is easily accessible compare to other HCPs. Added to it possesses good knowledge about medicine use and disposal. So some may offer eco-friendly info or take-back services.

Support Green Pharmacies

Support pharmacies and drug companies who are committed to reducing environmental impact (e.g., sustainable packaging, greener drug production).

Advocate for Change

Encourage local governments and health organizations to implement and promote better environmental drug policies.

Avoid Unnecessary Use of Over-the-Counter Drugs

Many people take OTC drugs like painkillers or antacids unnecessarily. This leads to increased production, use, and environmental excretion.

Looking Ahead

Ecopharmacovigilance is still evolving, but it’s becoming an essential part of environmental health strategies. With collaborative efforts from the healthcare industry, regulators, and the public, we can reduce the ecological footprint of lifesaving medicines.

References:

1. Ecopharmacovigilance: Ensuring Environmental Safety from Pharmaceuticals, Uppsala Reports, 15 Oct 2024, available form https://uppsalareports.org/articles/ecopharmacovigilance-ensuring-environmental-safety-from-pharmaceuticals/

2. The Impact of Pharmaceuticals Released to the Environment, United state environmental Protection Agency.

3. Dutta A, Banerjee A, Chaudhry S. Ecopharmacovigilance: Need of the hour. Indian J Pharm Pharmacol 2022;9(2):77-80.

4. Eapen JV, Thomas S, Antony S, George P, Antony J. A review of the effects of pharmaceutical pollutants on humans and aquatic ecosystem. Explor Drug Sci. 2024; 2:484–507. https://doi.org/10.37349/eds.2024.00058

5. OECD (2019), Pharmaceutical Residues in Freshwater: Hazards and Policy Responses, OECD Studies on Water, OECD Publishing, Paris, https://doi.org/10.1787/c936f42d-en

6. Paut Kusturica M, Jevtic M and Ristovski JT (2022), minimizing the environmental impact of unused pharmaceuticals: Review focused on prevention. Front. Environ. Sci. 10:1077974. Doi: 10.3389/fenvs.2022.1077974

7. Guideline on the environmental risk assessment of medicinal products for human use, Committee for Medicinal Products for Human Use (CHMP), European Medicine Agency.

8. Environmental Impact Review at CDER, 07 Jan 2025, US Food and Drug Administration, available fromhttps://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/environmental-impact-review-cder

MS

Could High-Dose Vitamin D Help Fight Early Multiple Sclerosis? New Evidence Says Yes

by with No Comment Disease & DrugsResearch

Written and Reviewed by Vikas Londhe M.Pharm (Pharmacology)

MS

A recent study published in JAMA on March 10, 2025, titled “High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial,” investigated the efficacy of high-dose cholecalciferol (vitamin D) as a monotherapy in reducing disease activity in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). This randomized clinical trial enrolled participants diagnosed with CIS, a condition characterized by a single episode of neurological symptoms indicative of MS. The objective was to determine whether high-dose vitamin D supplementation could delay or prevent the progression from CIS to clinically definite MS.​ The trial’s results indicated that participants receiving high-dose vitamin D exhibited a significant reduction in disease activity compared to those in the placebo group. Specifically, MRI scans revealed fewer new or enlarging lesions in the vitamin D group, suggesting a potential neuroprotective effect of high-dose cholecalciferol in the early stages of MS.

Link between Vitamin D and MS

Multiple sclerosis (MS) is a long-term disease that affects the central nervous system by damaging the protective covering of nerves (myelin). This damage disrupts nerve signals, causing symptoms that vary from mild fatigue to severe paralysis and cognitive issues. The exact cause is unknown, but it likely involves both genetics and environmental factors. MS affects over 2.8 million people worldwide and is a major cause of disability in young adults.

Vitamin D is a fat-soluble vitamin that is important for strong bones and maintaining calcium levels in the body. It also plays a role in regulating the immune system. Vitamin D works by interacting with a specific receptor Vitamin D receptor (VDR) found in many immune cells. Research suggests that it can affect the immune system by reducing the growth of certain T cells, supporting regulatory T cells, and influencing the production of inflammatory substances like cytokines. Because of these effects, scientists are interested in studying whether vitamin D supplements could help manage multiple sclerosis (MS), a disease linked to immune system dysfunction.

The D-Lay MS Trial (NCT01817166): The D-Lay MS trial was a rigorous, double-blind, placebo-controlled study conducted across 36 MS centers in France. Recruitment spanned from July 2013 to December 2020, with final follow-ups completed in January 2023. The study aimed to determine whether high-dose cholecalciferol (vitamin D3) could reduce disease activity in individuals diagnosed with CIS or early-stage relapsing-remitting MS (RRMS).

A total of 316 patients aged 18–55 years, diagnosed with CIS within the previous 90 days, were enrolled. Inclusion criteria required a serum vitamin D concentration below 100 nmol/L and MRI findings consistent with the 2010 MS diagnostic criteria. Notably, participants had not received any prior disease-modifying treatments.

Intervention and Study Groups: Participants were randomly assigned to one of two groups:

High-dose cholecalciferol (100,000 IU) every two weeks (n = 163)

Placebo group receiving a matching supplement (n = 153)

The intervention period lasted 24 months, during which disease activity and clinical outcomes were closely monitored.

Key Outcomes and Findings The primary endpoint of the study was disease activity, defined as the occurrence of relapses and/or MRI activity (new or contrast-enhancing lesions). Secondary outcomes included MRI-based disease activity measures, clinical relapses, and safety assessments.

Primary Outcome Results

60.3% of patients in the vitamin D group experienced disease activity, compared to 74.1% in the placebo group. The time to disease activity was significantly longer in the vitamin D group (432 days) compared to the placebo group (224 days).

MRI-Based Findings: Patients in the vitamin D group demonstrated significant reductions in MRI-based disease activity: MRI activity: 57.1% in the vitamin D group vs. 65.3% in the placebo group.

New lesion occurrence: 46.2% in the vitamin D group vs. 59.2% in the placebo group.

Contrast-enhancing lesions: 18.6% in the vitamin D group vs. 34.0% in the placebo group.

Clinical Outcomes and Safety While MRI-based improvements were evident, no significant differences in relapse rates were observed:

17.9% of patients in the vitamin D group experienced relapses vs. 21.8% in the placebo group

Regarding safety, severe adverse events were reported in 17 patients in the vitamin D group and 13 patients in the placebo group. However, none of the adverse events were directly attributed to vitamin D supplementation.

Interpretation and Clinical Implications

This study provides strong evidence that high-dose vitamin D can reduce MRI-based disease activity in CIS and early MS. These findings suggest potential neuroprotective and immunomodulatory effects, possibly delaying progression to clinically definite MS. However, the lack of significant impact on relapse rates indicates that vitamin D supplementation may not be a stand-alone treatment but could serve as an adjunct to existing disease-modifying therapies.

Conclusion and Future Directions

The D-Lay MS trial highlights the benefits of high-dose vitamin D (100,000 IU biweekly) in reducing MRI-based disease activity. Although it did not significantly impact relapse rates, the delayed onset of disease activity suggests its potential as an early intervention strategy. Further research is needed to optimize dosing, assess long-term safety, and evaluate the role of vitamin D in combination with other MS treatments.

References

  1. Feige J, Moser T, Bieler L, et al, Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats. Nutrients. 2020 Mar 16;12(3):783. Doi: 10.3390/nu12030783. PMID: 32188044; PMCID: PMC7146466.
  2. Aderinto, N., Olatunji, G., Kokori, E. et al.High-dose vitamin D supplementation in multiple sclerosis: a systematic review of clinical effects and future directions. Discov Med1, 12 (2024). https://doi.org/10.1007/s44337-024-00023-9
  3. Thouvenot E, Laplaud D, Lebrun-Frenay C, et al. High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial. JAMA.Published online March 10, 2025. doi:10.1001/jama.2025.1604

4. Sintzel, M.B., Rametta, M. & Reder, A.T. Vitamin D and Multiple Sclerosis: A Comprehensive Review. Neurol Ther 7, 59–85 (2018). https://doi.org/10.1007/s40120-017-0086-4

summer drinks

“Stay Hydrated the Natural Way: Best Summer Drinks from Ayurveda”

by with No Comment FoodWellness

Medically Written and Reviewed by Ayurvedacharya Dr. Gaurav Pathare (BAMS)

top-view-glass-with-hot-water-crystallized-sugar

In Ayurveda, the focus during the hot summer months is on cooling the body and balancing the excess heat that tends to build up. Ayurvedic cold drinks are typically made from cooling herbs, fruits, and spices to reduce inflammation, quench thirst, heat stroke, burning sensation and promote overall well-being. Here are some Ayurvedic cold drinks that are perfect for the summer season

Dhnayak Heem (Coriander Drink):

Dhanyak Heema is an Ayurvedic formulation that is primarily made from Dhanyaka (coriander) along with other ingredients, often designed to soothe internal heat and balance bodily functions.

Ingredients: 1 part of coriander coarse powder.

Preparation: Add the powder to 6 part of boiling water, cover, and let it cool. After cooling, crush the mixture and take it with the medicine.

Uses and Benefits

Antardaha (Burning Sensation inside the Body)

Dhanyak Heema is very effective in alleviating Antardaha, which refers to a burning sensation inside the body. This burning feeling can be associated with excess Pitta or heat in the body, and Dhanyak Heema’s cooling and soothing properties help to relieve this discomfort. It balances internal heat and can be used for conditions like gastritis, acid reflux, or fever-induced burning sensations.

Trushna (Excessive Thirst)

Dhanyak Heema is helpful for Trushna, or excessive thirst, especially when it is caused by heat-related conditions or dehydration. It works by cooling the body and providing hydration, helping to reduce the sensation of unquenchable thirst.

Strotovishodhan (Detoxification and Purification of Channels)

The term Strotovishodhan refers to the process of purifying the body’s channels (Strotas), and Dhanyak Heema helps cleanse and detoxify these channels. It particularly supports the Mutravahi (urinary) channels, acting as a diuretic, promoting healthy urinary function, and helping the body eliminate excess toxins through urination. This cleansing effect can also help in improving overall metabolism and bodily function.

Manuka Heem (Black raisin Drink)

Ingredients: 1 part of black raisins with seeds, 6 parts of water.

Preparation: Soak the black raisins and water together for 4-5 hours, then crush and strain. The strained water is Manuka Heem.

Sharkar Sherbat (Herbal Syrup)

Ingredients: Juices of Kokum (Garcinia Indica), Vala (Chrysopogon zizanioides), Amla (Phyllanthus Emblica), Gulabpush (Rose petals), Kevadpush (Pandanus Fascicularis), or other sour-sweet fruits, along with double the sugar and water (8 times).

Preparation: Mix the juices of the fruits, sugar, and water to create refreshing herbal syrup.

Panak Kalpana (Fruit Pulp Drink)

Ingredients: Sweet-sour fruits Kairi (raw mango), pomegranate, falsa (Grewia asiatica) Tamarind, grape, orange, pineapple, date, sugar or jaggery, and water (16 times the pulp).

Preparation: Cook or ripen the fruit, then blend the pulp with sugar or jaggery, and dilute with water.

Laja Manda (Puffed Rice Water Drink)

Laja Manda is a traditional Ayurvedic drink made from puffed rice (Laja), which is often mixed with water. This simple and effective preparation has several cooling and digestive benefits.

Ingredients: Saali lahya (popped rice/puffed rice) and Khadisakhar honey.

Preparation: Soak Saali lahya (puffed rice) in hot water (14 times the amount of lahya) overnight. In the morning, strain and mix with Khadisakhar honey.

Kapha & Pitta Hara (Balances Kapha and Pitta)

Laja Manda helps in balancing the Kapha and Pitta doshas. It is especially effective in cooling down the body, which can be beneficial for those with an excess of Pitta

(Heat) or Kapha (Dampness and Heaviness) by reducing the excess heat and moisture, it helps bring balance to both doshas.

Grahi (Astringent or Absorptive)

Laja Manda has an absorbing quality that helps in reducing excess moisture in the body. This quality can be especially beneficial when there is a need to manage conditions that involve the accumulation of fluids or dampness, such as edema or digestive disturbances.

Useful In

Pipasa (Excessive Thirst)

Laja Manda is particularly useful in alleviating Pipasa or excessive thirst. Its cooling properties help to quench thirst, especially when it is due to heat-related conditions, dehydration, or fever.

Jwara (Fever)

Laja Manda is commonly used in Jwara, or fever to cool the body. It helps lower body temperature, reduces the burning sensation that often accompanies fever, and helps with hydration, which is essential during illness.

Manth Kalpana (Sweet and Sour Fruit Drink)

Ingredients: A mixture of sweet and sour fruit juices like Kharjur (date), Amalaki (Indian gooseberry), Draksha (raisins), and others, along with water (4 times the juice).

Preparation: Mix and soak the ingredients in water for 2 hours, then churn and rub with hand. Strain through cloth to get the liquid.

Shadangapaniya (Aromatic Herbal Drink)

Ingredients: Nagarmotha (Sedge Root), Pittapapada (Fumitory), Aromatic Vala, Black Vala, Sandalwood, and Sunth (Dried Ginger) (3 gm each) with 1250 ml of boiling water.

Preparation: Mix all ingredients with boiling water and keep the mixture covered until cooled. Consume little by little.

Deepan (Increase Digestive Fire)

Shadangpaniya is known to stimulate and increase the digestive fire, or “Agni,” which is essential for proper digestion and metabolism in Ayurveda. Enhancing the Agni helps improve the body’s ability to digest food and absorb nutrients efficiently.

Pachan (Digestion)

This beverage is particularly useful in aiding the digestion process. It helps break down food and improves overall digestive function, which is beneficial for those suffering from indigestion or slow digestion.

Aamdoshharam (Relieves Ama or Toxins)

Shadangpaniya is effective in eliminating Ama (toxic substances or undigested food) from the body. In Ayurveda, Ama is considered a major cause of many diseases, so anything that helps in removing it is highly valued for overall health and well-being.

Useful In

Jwara (Fever)

Shadangpaniya is often recommended in cases of Jwara or fever, as it helps cool down the body and enhances digestion, which is often compromised during illness.

Pipasa (Excessive Thirst)

It helps quench excessive thirst (Pipasa), which can occur due to various factors such as dehydration or conditions that disturb the body’s fluid balance.

Daha (Burning Sensation)

Shadangpaniya can help alleviate the burning sensation or Daha, particularly when it occurs due to excess Pitta or heat in the body. Its cooling properties help soothe the body and bring down the internal heat.

Narikodaka (Coconut Water)

It is described in Ayurvedic texts for its various beneficial properties.

Singdha (Unctous): It has a moist and smooth texture, making it soothing and hydrating.

Madhur (Sweet): It has a naturally sweet taste, which contributes to its nourishing and restorative qualities.

Shukravardhak (Increases Semen): Coconut water is considered beneficial for reproductive health, promoting the production of semen or improving its quality.

Sheeta (Cold): It has a cooling effect on the body, making it ideal for hot climates or conditions that cause heat-related symptoms.

Laghu (Light): It’s light on the stomach, making it easy to digest and absorb without causing heaviness or discomfort

Useful in

Excessive Thirst (Trushna): Coconut water is often recommended to alleviate thirst, particularly when it’s caused by dehydration or excessive heat.

Vata and Pitta Disorders: It helps balance the Vata and Pitta doshas, which are often aggravated by heat, dryness, and stress. It is especially useful in soothing conditions like inflammation, irritability, and digestive issues.

Deepan (Increases Digestive Fire): Though it is considered cold, coconut water can aid in improving digestion, especially when digestive fire is weak.

Bastishodhan (Diuretic): It acts as a natural diuretic, promoting urination and helping in the elimination of toxins through the urinary tract.

References

1) Sharangdhar Samhita Madhyam Khand 4/7.

2) Bhaishajya Kalpana Vidnyan by Dr. Ram Chandra Reddy (Edition 2005, pages 197-198)

3) Bhaishajya Kalpana Vidnyan by Dr. Ram Chandra Reddy (Edition 2005, page 194)

4) Sharangdhar Samhita Madhyam Khand 2/174.

5) Sharangdhar Samhita Madhyam Khand 4/9-10, 11

6) Sharangdhar Samhita Madhyam Khand 2/158.

7) Ashtang Hridaya Sutrasthan 5/19

 

Women are playing yoga at the park. Exercising.

Ayurveda in spring: Detox, Diet & Daily Routine According to Vasant Ritucharya

by with No Comment LifestyleWellness
Medically Written and Reviewed by Ayurvedacharya Dr. Gaurav Pathare (BAMS)
Women are playing yoga at the park. Exercising.

Spring season (Vasant Ritu) – (March, April, first half of May)

This seasonal Ayurvedic regimen for spring provides a comprehensive approach to maintaining health and balance by addressing the body’s natural changes during the season.

State of Doshas in the Spring Season (Vasant Ritu)

Kapha: The predominant dosha during spring. Its excess leads to imbalances like congestion, sluggishness, and moisture buildup in the body.

Pitta: Generally stays in balance, supporting good digestion and metabolic function.

Vata: Weakens, which may reduce digestive fire (Agni) and decrease appetite

Dietary Guidelines (Ahara)

Focus on dry, light, sharp, hot, and pungent qualities to counter Kapha’s heaviness and moisture.

Stimulate digestive fire by consuming easily digestible foods.

Preferred Foods:

Grains: Old rice, brown rice, Jowar (sorghum), Millet.

Legumes: Roasted pulses like moong (Yellow moong dal), lentils, Tur (pigeon pea) Sandage, Usali.

Roasted Foods: Roasted meats (Goat, Chicken, etc.), Tandoori.

Vegetables: Spinach, Radish, Fenugreek, Brinjal, Shevga (Drumstick or Moringa Oleifera)

Spices: Turmeric, Cumin, Cinnamon, Pepper, Asafoetida, Mustard, Bay leaf.

Other Foods: Wheat flour, Gram, Older Grains, Boiled and Cooled Water.

Prohibited Foods:

Heavy and Cold Foods: Avoid Curd, Ice Cream, Lassi (Yogurt based sweet drink), Cold drinks, Sour and Fried Foods.

Sweets: Avoid rich sugar based sweets.

Dairy & Fermented Foods: Avoid Curd Rice, Cheese, Paneer.

Other Foods: Bananas, Tomatoes, Fish, Urad dal, Peas, and hydrogenated fats (dalda).

 Avoid Late Night Eating: Eating late can disrupt digestion

Lifestyle Recommendations (Vihar)

Langhan: Practice moderation in food intake with small, easily digestible meals.

Exercise: Engage in regular light exercises like walking or pranayama (breathwork). Avoid heavy exertion but aim to stimulate circulation.

Body Care: Rub the body with warm water to increase circulation and remove excess moisture. Take warm baths to soothe the body.

Sleep: Avoid daytime naps, as they can aggravate Kapha.

Panchakarma (Detoxification)

Vaman: Induced vomiting to help expel excess Kapha from the body and clear congestion.

Nasya: Nasal treatments using oils to clear sinuses and reduce mucus buildup.

Rasayan (Rejuvenation)

Triphala Rasayan: A traditional herbal remedy for detoxification and digestion.

Honey-Water: A natural tonic for balancing Kapha and improving digestion.

Overall Approach

The regimen reduces Kapha’s excess moisture and heaviness by focusing on stimulating, light, and easily digestible foods.

Regular light exercise and detoxification techniques (like Vaman and Nasya) help clear excess Kapha and boost vitality.

By avoiding Kapha-aggravating foods and focusing on digestive health, the body can stay balanced and energized during the spring season.

This holistic approach of diet, lifestyle, detox, and rejuvenation supports the body’s natural rhythms, helping to maintain optimal health during the transition of seasons.

Reference:

Ashtang Hridaya sutrasthan chapter 3 /19-25

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FDA Approves Blujepa: First-in-Class Topoisomerase Inhibitor Antibiotic for UTIs

by with No Comment Disease & Drugs

Written by Lavanya Chavhan (B.Pharm) and Aishwarya Shinde (B.Pharm)

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

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In a significant development in the fight against urinary tract infections (UTIs), the U.S. Food and Drug Administration (FDA) has approved Blujepa (gepotidacin), a groundbreaking oral antibiotic designed to treat uncomplicated UTIs in female patients aged 12 and older. This marks the first new class of oral antibiotics for UTIs in nearly three decades, offering hope to millions of women who suffer from recurrent infections that are increasingly resistant to traditional treatments.

Background and Need for New Treatments

UTIs are primarily caused by bacteria, most commonly Escherichia coli (E. coli) (75-95% of cases). Other pathogens include Klebsiella pneumoniae, Proteus mirabilis Staphylococcus saprophyticus (common in young women) and Enterococcus faecalis potentially affecting the bladder (cystitis), urethra (urethritis), or kidneys (pyelonephritis).

Conventional treatment for Uncomplicated UTIs includes first-line antibiotics Nitrofurantoin, Trimethoprim-sulfamethoxazole (TMP-SMX), Fosfomycin. Alternatives treatment includes Cephalexin and Amoxicillin-clavulanate if resistance is low.

In Complicated UTIs like UTI in pregnancies, diabetes, or kidney involvement (pyelonephritis) broad-spectrum antibiotics are implemented like Ciprofloxacin, Levofloxacin, and intravenous Ceftriaxone. More severe infections may need piperacillin/tazobactam, meropenem, ertapenem, or doripenem.

UTI is one of the most commonly affecting bacterial infection affecting 150 million people per year globally. Women are at higher risk (50-60% experience ≥1 UTI in their lifetime) due to shorter urethras. Elderly & catheterized patients also have increased susceptibility.

Antibiotic resistance is the rising concern in UTI treatment, resistance to TMP-SMX, fluoroquinolones (e.g., Ciprofloxacin), and beta-lactams complicated the treatment process. ESBL-producing E. coli which is resistant to penicillin/Cephalosporins is a growing concern and which can leads to longer infections, higher recurrence rates, and increased use of IV antibiotics.

These increased concerns of antibiotic resistance necessitating the development of new antibiotics with novel mechanisms of action.

Blujepa (Gepotidacin): A Novel Approach

Blujepa is developed by GlaxoSmithKline (GSK) is a novel first-in-class triazaacenaphthylene antibiotic that belongs to a new category called bacterial topoisomerase inhibitors. It exhibits a unique mechanism of action distinct from other antibiotics, targeting bacterial type II topoisomerases.

Gepotidacin selectively inhibits bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, both critical enzymes for DNA replication and transcription. Unlike fluoroquinolones (which stabilize topoisomerase-DNA cleavage complexes), gepotidacin blocks the ATP-independent strand-passage reaction, preventing DNA relaxation and decatenation.

It binds to a novel site on the GyrB (gyrase) and ParE (topoisomerase IV) subunits, distinct from fluoroquinolone binding sites.

This reduces the likelihood of cross-resistance with existing antibiotics. By interfering with DNA replication and repair, gepotidacin causes lethal double-stranded DNA breaks, leading to bacterial cell death.

This unique mechanism reduces the likelihood of antimicrobial resistance, making it a promising solution for recurrent or treatment-resistant UTIs

Clinical Trials and Approval

The FDA’s approval of Blujepa was based on results from two pivotal Phase III clinical trials, EAGLE-2 and EAGLE-3.

The EAGLE-2 trial was a Phase III, randomized, double-blind study evaluating the efficacy and safety of gepotidacin. Trial was conducted across multiple centres worldwide, the trial enrolled non-pregnant females weighing at least 40 kg who exhibited symptoms such as dysuria, frequency, urgency, or lower abdominal pain, along with evidence of urinary nitrite or pyuria. Participants were randomly assigned to receive either oral gepotidacin (1500 mg twice daily for 5 days) or oral nitrofurantoin (100 mg twice daily for 5 days). The primary endpoint was therapeutic success, defined as complete symptom resolution and microbiological eradication of the uropathogen without the need for additional antimicrobial treatment. ​ In the EAGLE-2 trial, therapeutic success was achieved in 50.6% of patients treated with gepotidacin compared to 47.0% of those receiving nitrofurantoin demonstrating non-inferiority of gepotidacin to nitrofurantoin.

EAGLE-3 trial was randomized, double-blind, double-dummy, non-inferiority trial compared gepotidacin (1500 mg twice daily for 5 days) to nitrofurantoin (100 mg twice daily for 5 days), a standard uUTI treatment. The results demonstrated that gepotidacin was statistically superior to nitrofurantoin in achieving therapeutic success at the test-of-cure visit (days 10–13). Specifically, therapeutic success was observed in 58.5% of patients receiving gepotidacin compared to 43.6% in the nitrofurantoin group.

Safety Profile

Blujepa carries the warning signs of QTc prolongation and hypersensitivity reactions. The safety profile of gepotidacin was consistent with previous studies. Common adverse events were gastrointestinal-related, such as diarrhea (16%) and nausea (4%). Most of these adverse events were mild or moderate, with severe events occurring in less than 1% of participants.

Impact and Future Directions

The approval of Blujepa is a crucial milestone in addressing the growing challenge of antibiotic resistance in UTIs. It provides a new treatment option for patients experiencing recurrent infections and offers hope for reducing the strain on healthcare systems.

As noted by GSK’s Chief Scientific Officer, Tony Wood, this approval is significant for women who face recurrent infections and rising resistance rates.

In conclusion, the FDA’s approval of Blujepa marks a significant advancement in the treatment of uncomplicated UTIs, offering a new and effective option for managing these common infections. As the first new oral antibiotic for UTIs in nearly 30 years, Blujepa represents a promising step forward in combating antimicrobial resistance and improving patient outcomes.

References

1. Blujepa (gepotidacin) approved by US FDA for treatment of uncomplicated urinary tract infections (uUTIs) in female adults and paediatric patients 12 years of age and older, GSK, 25 March 2025, available from https://www.gsk.com/en-gb/media/press-releases/blujepa-gepotidacin-approved-by-us-fda-for-treatment-of-uncomplicated-urinary-tract-infections/

2. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection, and treatment options. Nat Rev Microbiol. 2015 May; 13(5):269-84. DOI: 10.1038/nrmicro3432. Epub 2015 Apr 8. PMID: 25853778; PMCID: PMC4457377

3. Bono MJ, Leslie SW. Uncomplicated Urinary Tract Infections. [Updated 2025 Feb 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.  Available from: https://www.ncbi.nlm.nih.gov/books/NBK470195/

4. Sabih A, Leslie SW. Complicated Urinary Tract Infections. [Updated 2024 Dec 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.  Available from: https://www.ncbi.nlm.nih.gov/books/NBK436013/

5. Mareș C, Petca RC, Popescu RI, et al, Update on Urinary Tract Infection Antibiotic Resistance-A Retrospective Study in Females in Conjunction with Clinical Data. Life (Basel). 2024 Jan 9;14(1):106. Doi: 10.3390/life14010106. PMID: 38255721; PMCID: PMC10820678

6. Emina K. Sher, Amina Džidić-Krivić, et al, Current state and novel outlook on prevention and treatment of rising antibiotic resistance in urinary tract infections, Pharmacology & Therapeutics, Volume 261, 2024, 108688, https://doi.org/10.1016/j.pharmthera.2024.108688

7. Blujepa (gepotidacin), Highlights Of Prescribing Information, available from https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218230s000lbl.pdf

8. Wagenlehner, Florian et al, Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials, The Lancet, Volume 403, Issue 10428, 741 – 755

9. Clinical Implications, Study Takeaways of Gepotidacin for Uncomplicated UTIs, 28 March 2025, Contagion Live, available from https://www.contagionlive.com/view/clinical-implications-study-takeaways-of-gepotidacin-for-uncomplicated-utis