FDA Approves Ropeginterferon Alfa-2b-njft for Polycythemia Vera

FDA

The FDA has approved ropeginterferon alfa-2b-njft (Besremi) for use as a treatment in patients with polycythemia vera.¹

The regulatory decision was based on safety from the PEGINVERA and PROUD/ CONTINUATION-PV studies and efficacy findings from the PEGINVERA clinical study program.

Results showed that following 7.5 years of treatment with ropeginterferon alfa-2b-njft, 61% of patients achieved a complete hematological response, which was defined as hematocrit less than 45% without phlebotomy for at least 2 months since last phlebotomy, platelet counts of 400 x 10⁹/L or less, leukocytes of 10 x 10⁹/L or less, and normal spleen size.

Notably, 80% of patients experienced a hematological response with the agent; this was based on objective laboratory parameters only, with the exclusion of normal spleen size and thrombosis. These parameters are the most frequently used metrics to make clinical decisions.

In the pooled safety population of patients treated with ropeginterferon alfa-2b-njft , the most common toxicities included influenza-like illness, arthralgia, fatigue, pruritis, nasopharyngitis, and musculoskeletal pain. Serious adverse reactions included urinary tract infection, transient ischemic attack and depression.

“The FDA approval of ropeginterferon alfa-2b-njft (Besremi) for people with polycythemia vera represents the next step in advancing patient care as it provides a critical addition to managing not only symptom burden and near-term complications, but also treating the cancer early, which may help reduce the risk of disease progression over time,” Srdan Verstovsek, MD, PhD, director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, Department of Leukemia at the University of Texas MD Anderson Cancer Center, stated in a press release. “With the availability of an FDA-approved, next-generation interferon for this indication, it’s time that we focus on preserving the long-term health of patients with polycythemia vera.”

Ropeginterferon alfa-2b is a novel, long-acting, mono-pegylated proline interferon that was designed to have an optimized profile that would allow for improved pharmacokinetic properties. The agent was also developed to have more favorable tolerability and convenience versus conventional interferons. The agent was developed to be given once every 2 weeks or once every 4 weeks during long-term maintenance.³

PROUD-PV, and CONTI-PV, which was the extension study, were open-label, controlled, phase 3 trials that were conducted in 48 clinics in Europe. To be eligible for enrollment, patients had to be 18 years of age or older with an early-stage polycythemia vera diagnosis per the World Health Organization 2008 criteria.

In the trial, participants were randomized 1:1 to either subcutaneous ropeginterferon alfa-2b, which was given biweekly at a starting dose of 100 μg, or oral hydroxyurea at a starting daily dose of 500 mg. At 1 year, patients had the opportunity of enrolling to the extension portion of the research, the CONTI-PV trial.

The primary objective of PROUD-PV was to establish noninferiority of ropeginterferon alfa-2b versus hydroxyurea in terms of complete hematological response with normal spleen size at 12 months. The coprimary end points of CONTI-PV comprised complete hematological response with normalization of spleen size and improved disease burden, with regard to splenomegaly, microvascular disturbances, pruritus, and headache.

A total of 306 participants were enrolled to the trial between September 17, 2013 and March 13, 2015. Of these patients, 257 underwent randomization, with 127 patients treated in each arm; however, 3 patients in the control arm ended up withdrawing consent. A total of 171 patients went on to participate in the CONTI-PV trial. The median follow-up was 182.1 weeks and 164.5 weeks in the investigational and control arms, respectively.

In PROUD-PV, 21% (n = 26) of patients who received ropeginterferon alfa-2b (n = 122) and 28% (n = 34) of those who were given standard treatment (n = 123) met the composite primary end point of complete hematological response. Additionally, improved disease burden was met in 53% (n = 50) of patients in the investigational arm versus 38% (n = 28) of those in the hydroxyurea arm (n = 74) at 36 months (P = .044).

Additional results showed that complete hematological response without the spleen criteria in the investigational and standard arms were 43% (n = 53) of 123 patients compared with 46% (n = 57) of 125 patients, respectively, at 12 months (P = .63; PROUD-PV). At 36 months, these were 71% (n = 67) of 95 patients compared with 51% (n = 38) of 74 patients, respectively (P =.012; CONTI-PV).

“We are incredibly proud to deliver on our goal of bringing treatments like ropeginterferon alfa-2b-njft to the polycythemia vera community where there is clear unmet need for more effective, tolerable and durable treatments to preserve patients’ health and well-being,” Ko-Chung Lin, PhD, co-founder and chief executive officer for PharmaEssentia and inventor of ropeginterferon alfa-2b-njft, stated in a press release. “As we begin working closely with the community to integrate this important treatment into clinical practice, we also continue to expand our scientific efforts to unlock the full potential of our pioneering molecule.”

References

1. US FDA approves BESREMI (ropeginterferon alfa-2b-njft) as the only interferon for adults with polycythemia vera. News release. PharmaEssentia Corporation. November 12, 2021. Accessed November 12, 2021. https://bwnews.pr/3nbXCYO
2. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7(3):e196-e208. doi:10.1016/S2352-3026(19)30236-4
3. US FDA accepts PharmaEssentia’s application for ropeginterferon alfa-2b to treat polycythemia vera. News release. PharmaEssentia Corporation. June 4, 2020. Accessed December 3, 2020. https://yhoo.it/30fZcxA.