The FDA has granted approval to Besremi (ropeginterferon alfa-2b), a novel interferon drug developed by PharmaEssentia, marking it as the first drug therapy specifically indicated for polycythemia vera. This regulatory decision offers a new treatment avenue for patients with this rare blood cancer, which can lead to severe cardiovascular complications if left unmanaged.
Mechanism of Action and Clinical Efficacy
Besremi is an engineered version of interferon alpha, a signaling protein that modulates the immune system. While the precise mechanism by which Besremi addresses polycythemia vera is not fully elucidated, it is believed to function by binding to interferon alpha receptors. This interaction initiates a signaling cascade that ultimately reduces blood cell production in the bone marrow. The drug is administered via subcutaneous injection every two weeks, with the potential for reduced frequency (every four weeks) if patients maintain stable red blood cell levels for at least a year.
The approval was supported by data from a seven-and-a-half-year open-label study involving 51 patients who received Besremi for an average of five years. The primary endpoint was the achievement of a complete hematological response, defined as a red blood cell volume of less than 45% without recent phlebotomy, normal white cell and platelet counts, normal spleen size, and absence of blood clots. Results indicated that 61% of patients achieved this comprehensive response.
Safety Profile and Warnings
The clinical trial identified several side effects associated with Besremi, including elevated liver enzymes, reduced white blood cell and platelet counts, joint pain, fatigue, and upper airway infections. The FDA has issued a black box warning for Besremi, highlighting the potential for severe adverse reactions such as urinary tract infection, depression, and stroke-like attacks. The warning advises clinicians to closely monitor patients for neuropsychiatric, autoimmune, ischemic, and infectious disorders, and to discontinue treatment if symptoms worsen. The drug also carries a risk of harm to unborn fetuses, necessitating pregnancy testing for women of childbearing potential before initiation of treatment.
Polycythemia Vera: Disease Context and Current Treatments
Polycythemia vera is characterized by a mutation in bone marrow stem cells, leading to an overproduction of red blood cells. This results in abnormally thick blood, increasing the risk of blood clots, heart attack, and stroke. According to the FDA, the condition affects approximately 6,200 Americans annually. Current treatment options include phlebotomy to reduce red blood cell count and chemotherapy or other drugs to suppress blood cell formation. However, some of these therapies carry an increased risk of leukemia.
Regulatory History and Availability
The FDA's approval of Besremi follows an initial rejection in March, which PharmaEssentia attributed to COVID-19-related travel restrictions that delayed manufacturing facility inspections. The company resubmitted its application in May. Besremi had previously received approval from the European Medicines Agency in 2019 and is also approved in Taiwan and South Korea. PharmaEssentia anticipates making the drug available in the U.S. in the coming weeks. Furthermore, Besremi is currently in Phase 3 clinical trials for essential thrombocythemia, another condition characterized by excessive platelet production.
