Among phlebotomy-dependent patients with polycythemia vera, the addition of rusfertide to standard-of-care treatment reportedly elicited encouraging responses compared to placebo plus standard-of-care treatment.
Positive topline results from the phase 3 VERIFY study were announced in a news release issued by Protagonist Therapeutics and Takeda.
Rusfertide, described in the news release as a first-in-class investigational hepcidin mimetic peptide therapeutic, has already received Orphan Drug designation and Fast Track designation from the Food and Drug Administration (FDA), according to the companies.
According to the news release, 77% of patients treated with rusfertide showed a clinical response to treatment, compared to 33% of patients who received placebo, during weeks 20 to 32 of the study. A response was defined as the absence of phlebotomy eligibility.
Glossary:
Orphan Drug designation: a designation issued by the FDA to a drug or biological product to prevent, diagnose or treat a rare disease or condition, qualifying sponsors for incentives such as tax credits, exemption from fees and a potential window of market exclusivity, according to the FDA.
Fast Track designation: a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need, in order to get new drugs to patients sooner, according to the FDA.
Many patients with polycythemia vera, the news release noted, are at increased risk for life-threatening cardiovascular and thrombotic events and may need to regularly undergo phlebotomy — described as a process of removing blood to manage elevated levels of hematocrit, or the percentage of red blood cells in the blood — and cytoreductive therapies.
Rusfertide, according to the National Cancer Institute, mimics endogenous hepcidin, a protein primarily produced in hepatocytes in the liver and increases hepcidin levels. The drug may work to normalize iron levels.
There was a mean of 0.5 phlebotomies per patient in the rusfertide arm of the VERIFY trial versus 1.8 phlebotomies per patient in the placebo arm in weeks 0 to 32, according to the news release, which further stated that hematocrit control and patient-reported outcomes were also achieved with statistical significance.
The companies also noted that rusfertide was found to be well tolerated in the trial, with no new safety signals observed. The majority of side effects were grade 1 (mild) to 2 (moderate) injection site reactions, and all serious side effects were found to not be related to the drug. Additionally, there was no evidence of increased cancer risk among patients treated with rusfertide versus those who received placebo.
“The positive results of the phase 3 VERIFY study… provide compelling evidence of the potential for rusfertide as a first-in-class erythrocytosis-specific agent to address unmet medical needs in patients with PV who are unable to achieve adequate hematocrit control despite standard of care treatments,” said Dr. Arturo Molina, Chief Medical Officer of Protagonist. “We plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025. We are immensely grateful to the patients, study staff and principal investigators who made the VERIFY study possible.”
“We are encouraged by these results and excited about the potential of rusfertide to help patients living with [polycythemia vera]. These patients may experience a high treatment burden, and severe symptoms can impact their quality of life,” said Dr. Andy Plump, President of R&D at Takeda. “We are deeply committed to bringing additional treatment options to those living with blood cancers, including myeloid cancers such as PV.”
“The totality of impressive clinical data to date shows that rusfertide has the potential for meaningful positive impact on the lives of patients with PV,” said Dinesh V. Patel, President and Chief Executive Officer at Protagonist. “We look forward to working with our partner, Takeda, to submit our findings to the regulatory agencies. Today’s study results also mark a critical inflection point in Protagonist’s decade long journey in the hepcidin program and further validates our platform and expertise in innovating highly differentiated peptide-based medicines to fulfill unmet medical needs.”
The phase 3 VERIFY trial is a three-part trial studying rusfertide among 293 patients with polycythemia vera over 156 weeks. According to its listing on clincialtrials.gov, the trial has an estimated study completion date of June 2025.
Polycythemia vera, according to the Mayo Clinic, is a type of blood cancer that causes a patient’s bone marrow to make too many red blood cells. These cells can, in turn, thicken patients’ blood and slow its flow, which may lead to issues such as blood clots.
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