FDA Issues Complete Response Letter for Ropeginterferon Alfa-2b for Polycythemia Vera

FDA

The FDA has issued a complete response letter (CRL) regarding the biologics license application (BLA) for ropeginterferon alfa-2b-njft for the treatment of patients with polycythemia vera, according to an announcement issued by PharmaEssentia Corporation.¹

The regulatory agency cited that COVID-19–related travel restrictions resulted in delayed pre-approval inspection of the company’s manufacturing facility in Taiwan. Moreover, the agency asked for more data regarding the administration format of the drug. However, no concerns were raised regarding the clinical profile of the agent.

“We are confident that we can work with the agency to address the requests highlighted in the response letter and resubmit in an expeditious manner,” Meredith Manning, US General Manager at PharmaEssentia Corporation, stated in a press release. “We remain fully committed to introducing ropeginterferon alfa-2b-njft to the US polycythemia vera community.”

In June 2020, the FDA accepted the BLA for the novel pegylated interferon for use in patients with polycythemia vera in the absence of symptomatic splenomegaly based on data yielded from the phase 3 PROUD/CONTI-PV trial (NCT02218047). Here, patients with polycythemia vera either received ropeginterferon alfa-2b (n = 95) or hydroxyurea/best available therapy (BAT; n = 74). Results indicated that at 36 months, ropeginterferon alfa-2b elicited a higher complete hematological response rate vs hydroxyurea/BAT, at 70.4% vs 51.4%, respectively.²

Moreover, response rates with the pegylated interferon were found to steadily increase over 24 months of treatment; they were found to be maintained after 36 months. After 36 months, 66% of those in the experimental arm achieved a molecular response vs 27% of those in the control arm. Molecular responses were closely related to complete hematological responses.

The toxicity rates proved to be similar between the 2 treatment arms. The most commonly experienced adverse effects that were determined to be associated with treatment included anemia, thrombocytopenia, and leukopenia.

The agent is also under investigation in the open-label, multicenter, phase 3 CONTINUATION-PV trial (NCT02218047), which is an extension of the phase 3 PROUD-PV trial (NCT01949805). Data from the trial presented during the 2020 ASH Annual Meeting & Exposition indicated that patients who were given the pegylated interferon had a higher likelihood of being phlebotomy free in the fourth or fifth year of treatment vs those given BAT.³

Specifically, 55.8% of patients given ropeginterferon achieved a complete hematologic response vs 44.0% of those given BAT at 5 years (P = .0974). Moreover, rates of complete hematologic response with last observation were found to have been carried forward at year 5; these rates were 72.6% in the experimental arm vs 52.6% in the control arm, a difference that was determined to be statistically significant (P = .004). In the fifth year of treatment, the majority or 81.8% of those in the experimental arm maintained hematocrit levels of less than 45% without the need for phlebotomy vs 63.2% of those in the control arm (P = .01).

Additionally, interim data from the phase 2 Low-PV trial (NCT03003325) demonstrated that more patients with low-risk polycythemia vera who received ropeginterferon alfa-2b were able to maintain hematocrit levels at or below 45% vs those who received monthly phlebotomy alone.⁴ Specifically, 84% of patients who were given the pegylated interferon maintained hematocrit levels at or below 45% without any signs of progressive disease vs 60% of those who underwent phlebotomy alone. Due to these positive findings, the Data and Safety Monitoring Board made the decision to close the trial early.

Previously, the FDA granted ropeginterferon alfa-2b an orphan drug designation for use in patients with polycythemia vera. In February 2019, the agent was approved by the European Commission for marketing in the European Union as a single agent in adults with polycythemia vera without symptomatic splenomegaly.

References

1. PharmaEssentia provides US regulatory update on ropeginterferon alfa-2b-njft for the treatment of polycythemia vera. News release. PharmaEssentia Corporation. March 14, 2021. Accessed March 15, 2021. https://bit.ly/3vv6GKD
2. US FDA accepts PharmaEssentia’s application for ropeginterferon alfa-2b to treat polycythemia vera. News release. PharmaEssentia Corporation. June 4, 2020. Accessed March 15, 2021. https://yhoo.it/30fZcxA
3. Gisslinger H, Klade C, Georgiev P, et al. Long-term use of ropeginterferon alpha-2b in polycythemia vera: 5-year results from a randomized controlled study and its extension. Blood. 2020;136(suppl 1):33. doi:10.1182/blood-2020-1336973
4. Barbui T, Vannucchi AM, De Stefano V, et al. Phase II randomized clinical trial comparing ropeginterferon versus phlebotomy in low-risk patients with polycythemia vera. Results of the pre-planned interim analysis. Presented at: EHA25 Virtual; June 11-21, 2020. Abstract LB2602.