How I diagnose and treat neonatal thrombocytopenia
Rusfertide Earns Breakthrough Therapy Designation In Polycythemia Vera
The FDA has granted rusfertide breakthrough therapy designation for patients with polycythemia vera, a step that could speed its path to approval.
The FDA granted rusfertide breakthrough therapy designation for patients with polycythemia vera.
An investigational drug called rusfertide may soon offer a new treatment option for people living with polycythemia vera, a rare blood cancer that causes the body to produce too many red blood cells. Protagonist Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted rusfertide breakthrough therapy designation, a step that could speed its path to approval.
This designation adds to rusfertide's earlier orphan drug and fast track statuses, all of which provide regulatory advantages designed to help new therapies reach patients more quickly. In the news release, Protagonist said it plans to file a new drug application with the FDA in the fourth quarter of 2025.
Rusfertide is a first-in-class therapy that acts as a hepcidin-mimetic peptide. In polycythemia vera, high red blood cell counts lead to thickened blood, which increases the risk of blood clots, stroke and other serious complications. Standard care often includes medications such as hydroxyurea, interferon or ruxolitinib, along with regular phlebotomies (blood draws) to keep hematocrit levels under control. However, many patients continue to struggle with uncontrolled blood counts, treatment side effects, and disease-related fatigue.
By mimicking hepcidin, a natural hormone that regulates iron in the body, rusfertide helps reduce excess red blood cell production. In clinical trials, the therapy has shown the ability to control hematocrit levels, reduce the need for frequent phlebotomies and improve symptoms such as fatigue.
Positive Results from Phase 3 VERIFY Trial of Rusfertide in Polycythemia VeraThe FDA's decision was supported by results from the global phase 3 VERIFY trial, which enrolled 293 patients with polycythemia vera. VERIFY is designed as a three-part, placebo-controlled study lasting 156 weeks, testing rusfertide in patients who remain dependent on phlebotomy despite standard treatment.
At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, 32-week data from VERIFY were presented during a plenary session, underscoring the drug's potential to change treatment practice.
According to the news release from Protagonist, patients who received rusfertide plus their current therapy achieved strong results across both primary and secondary trial end points. These included reliable hematocrit control, fewer phlebotomy procedures and meaningful improvements in patient-reported outcomes such as energy and fatigue levels.
"We are very pleased with the FDA's decision, which highlights rusfertide's potential to demonstrate substantial improvement over available therapies," said Dr. Dinesh V. Patel, president and CEO of Protagonist Therapeutics, in the news release. "We remain on track to submit our NDA by the end of this year."
Dr. Arturo Molina, chief medical officer at Protagonist, added in the news release, "The comprehensive data provide compelling evidence that rusfertide may help patients with polycythemia vera who cannot achieve adequate hematocrit control with standard treatments."
FDA Designations and What They Mean for Rusfertide in Polycythemia VeraBreakthrough therapy designation is granted to experimental treatments that show early evidence of providing a significant benefit over current options for serious conditions. It makes a therapy eligible for closer FDA guidance, faster development timelines and priority review.
Orphan Drug status, which rusfertide received in 2020, is given to medicines targeting rare diseases. It can provide additional benefits such as market exclusivity and tax incentives. Fast track designation helps speed the FDA review process. Together, these designations position rusfertide for an accelerated path toward potential approval.
All patients from the controlled portion of the VERIFY study have now moved into the open-label extension, where researchers are continuing to track long-term safety and efficacy.
If approved, rusfertide could become the first therapy of its kind for polycythemia vera. For patients who rely heavily on phlebotomy or struggle to maintain safe hematocrit levels on current drugs, rusfertide may represent a new option that directly targets the underlying biology of the disease.
ReferencesFor more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here.
NewsletterStay up to date on cancer updates, research and education
FDA Grants Orphan Status To Novel JAK2 Inhibitor For Polycythemia Vera
VGT-1849B receives FDA orphan drug designation, promising a targeted treatment for polycythemia vera with improved safety and efficacy.
The US FDA has granted orphan drug designation to VGT-1849B, an investigational selective JAK2 inhibitor, for the treatment of polycythemia vera (PV).1
This designation is a significant regulatory milestone that facilitates the development of therapies for rare diseases and signals a promising new direction in the management of this chronic myeloproliferative disorder. The investigational drug's novel mechanism, a selective peptide nucleic acid-based antisense oligonucleotide (ASO), aims to provide a more targeted therapeutic approach with a potentially improved safety profile compared to current JAK inhibitor therapies.
Polycythemia vera is a rare, chronic myeloproliferative neoplasm characterized by the overproduction of myeloid lineage cells, particularly erythrocytes, which can lead to increased blood viscosity, thrombosis, and a heightened risk of cardiovascular events. The disease is also associated with the release of pro-inflammatory cytokines, contributing to symptoms like pruritus and fatigue. In more than 95% of patients, the disease is driven by the JAK2 V617F gain-of-function mutation, which results in aberrant and uncontrolled JAK2 signaling. The prevalence of PV in the United States is estimated to be between 44 and 57 per 100,000 people.
Existing treatments for PV often focus on controlling hematocrit levels to prevent complications. Therapies targeting the JAK-STAT pathway, which is aberrantly activated by the JAK2 mutation, have demonstrated efficacy in managing both hematologic parameters and disease-related symptoms. However, current JAK inhibitors, such as ruxolitinib (Jakafi), fedratinib (Inrebic), momelotinib (Ojjaara), and pacritinib (Vonjo), are not exclusively selective for JAK2. Due to the highly conserved structure of the catalytic sites of protein kinases, these drugs can inhibit other JAK family members (JAK1, JAK3, and TYK2) or other kinases, leading to off-target effects and a spectrum of adverse events, including an increased risk of infection.
A close-up of red blood cells flowing through a vein: © catalin - stock.Adobe.Com
VGT-1849B is being developed to address these limitations. Unlike small-molecule JAK inhibitors, VGT-1849B is a peptide nucleic acid-based ASO that utilizes a unique OliPass Peptide Nucleic Acid (OPNA) backbone chemistry. This design allows it to selectively target and bind to JAK2 mRNA, effectively reducing JAK2 protein production. By intervening at the mRNA level, VGT-1849B is designed to specifically downregulate the JAK2 protein, including the mutant V617F variant, without inhibiting other kinases. This precision is expected to suppress the aberrant hematopoiesis, reducing the production of red blood cells, neutrophils, and platelets while potentially mitigating the systemic toxicities associated with off-target kinase inhibition.
If clinical development proves successful, the highly selective nature of VGT-1849B could translate into a more favorable safety profile, which would be a significant advantage for patients with PV. A treatment that minimizes the risk of infection and other side effects could substantially improve a patient's quality of life and long-term adherence to therapy. The agent also offers the potential for a convenient, infrequent dosing schedule, which could further enhance patient compliance and overall management of this chronic condition.
The FDA's Orphan Drug Designation is a regulatory status granted to drugs and biologics that are intended for the treatment, diagnosis, or prevention of rare diseases or conditions that affect fewer than 200,000 people in the US.2 This designation provides various incentives to the drug developer, including tax credits, user fee waivers, and a period of market exclusivity upon approval. This status underscores the significant medical need for new therapeutic options in PV and signals that the FDA has acknowledged VGT-1849B's potential to address this need.
What is polycythemia vera (PV)?Polycythemia vera is a rare, chronic myeloproliferative neoplasm, a type of blood cancer, where the bone marrow produces too many red blood cells, as well as sometimes white blood cells and platelets. This overproduction leads to increased blood viscosity, which raises the risk of blood clots (thrombosis) and serious cardiovascular events. Patients often experience symptoms like pruritus (itching) and fatigue due to the release of pro-inflammatory cytokines. In over 95% of cases, PV is caused by a specific genetic mutation called JAK2 V617F, which results in uncontrolled signaling in the JAK-STAT pathway. The estimated prevalence of PV in the United States is between 44 and 57 per 100,000 people.
What is VGT-1849B and how does it work?VGT-1849B is a novel, investigational selective JAK2 inhibitor that has been granted orphan drug designation by the FDA for the treatment of polycythemia vera. Unlike current small-molecule JAK inhibitors, VGT-1849B is a peptide nucleic acid-based antisense oligonucleotide (ASO) that utilizes OliPass Peptide Nucleic Acid (OPNA) backbone chemistry. This unique design allows it to selectively target and bind to JAK2 mRNA, thereby reducing the production of the JAK2 protein, including the mutant V617F variant. By intervening at the mRNA level, VGT-1849B aims to specifically downregulate the JAK2 protein without affecting other kinases, offering a more targeted therapeutic approach.
How does VGT-1849B differ from existing JAK inhibitor therapies for PV?Existing JAK inhibitor therapies, such as ruxolitinib, fedratinib, momelotinib, and pacritinib, are not exclusively selective for JAK2. Due to the conserved structure of protein kinase catalytic sites, these drugs can inhibit other JAK family members (JAK1, JAK3, and TYK2) or other kinases, leading to off-target effects and a range of adverse events, including an increased risk of infection. VGT-1849B, as a selective peptide nucleic acid-based ASO, is designed to specifically target and reduce JAK2 mRNA, which should result in highly selective inhibition of JAK2 protein production. This precision is expected to avoid the off-target effects seen with current treatments, potentially leading to a more favorable safety profile.
This article was generated with assistance from Google Gemini and NotebookLM. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.
REFERENCES: 1. Vanda Pharmaceuticals Announces FDA Granted Orphan Drug Designation for VGT-1849B, a Novel and Selective Candidate for the Treatment of Polycythemia Vera. News release. Vanda Pharmaceuticals. August 28, 2025. Accessed August 28, 2025. Https://tinyurl.Com/32zau7ba 2. Designating an Orphan Product: Drugs and Biological Products. US FDA. Updated August 12, 2024. Accessed August 28, 2025. Https://tinyurl.Com/5ckfaxtvPolycythemia Vera - Latest Research News And Features
Just a moment...This request seems a bit unusual, so we need to confirm that you're human. Please press and hold the button until it turns completely green. Thank you for your cooperation!
Press and HoldPress and hold the button
If you believe this is an error, please contact our support team.
167.71.87.121 : b88ed7ae-d659-4048-a0a3-53bf83a9
Comments
Post a Comment