BLA Resubmission for Ropeginterferon alfa-2b Accepted by FDA for Treatment of Patients with PV

A Biologics License Application (BLA) for their drug ropeginterferon alfa-2b-njft as treatment of patients with the rare blood cancer polycythemia vera (PV) has been resubmitted to the FDA for consideration according to a press release by PharmaEssentia USA Corporation.¹

The resubmission of the BLA for ropeginterferon alfa-2b-njft comes after the FDA issued a complete response letter to the company in March citing COVID-19 travel restrictions delaying the approval process, as officials could not properly inspect the Taiwanese manufacturing facility. Moreover, the agency wanted to see additional data regarding the administration format of the product, but no concerns were raised by the FDA regarding the clinical profile of the drug.

“We are confident that we have thoroughly addressed the information requests and look forward to engaging with the Agency throughout its review of our application, which we believe supports a positive profile for ropeginterferon alfa-2b-njft,” said Meredith Manning, US General Manager, in a press release announcing the resubmission of the BLA. As of now, ropeginterferon alfa-2b has orphan drug status in the treatment of PV in the US and is approved in Europe under the name Besremi.

The original BLA submission for ropeginterferon alfa-2b-njft approval accepted by the FDA for approval review was based on results from the phase 3 PROUD/CONTINUATION-PV clinical trial (NCT01949805; NCT02218047), presented at the 2020 American Society of Hematology Annual Meeting, that showed ropeginterferon alfa-2b-njft had a high and durable hematological response in patients over 36 months, compared to hydroxyurea (Siklos).²

306 patients were enrolled in the study and 257 patients were randomly assigned treatment, with 171 patients rolling over to the CONTINUATION-PV trial. In the PROUD-PV group, 21% of the patients in the ropeginterferon alfa-2b arm met the study endpoint of complete hematological response with normal spleen size, whereas 28% of the patients on standard therapy met this endpoint.

In the CONTINUATION-PV group, 53% of patients on ropeginterferon alfa-2b-njft met complete hematological response with improved disease burden markers, while only 38% of patients in the hydroxyurea group met this standard (P = 0.044). Excluding the spleen size criteria, 43% of patients on ropeginterferon alfa-2b had complete hematological response compared to 46% on the standard of care group in the PROUD-PV trial. In the patients that were on the CONTINUATION-PV trial, 71% of patients on ropeginterferon alfa-2b had a complete hematological response compared to 58% on the standard of care.

The most common grade 3 and 4 treatment-related adverse events (TRAEs) were increased γ-glutamyl transferase (6%) and increased alanine aminotransferase (3%) in the ropeginterferon alfa-2b group. Leucopenia (5%) and thrombocytopenia (4%) were the most common TRAEs in the standard therapy group. Treatment-related serious AEs occurred in 2% of patients on ropeginterferon alfa-2b and 4% in the hydroxyurea group. Only 1 treatment related-death, acute leukemia, was reported in the hydroxyurea group.

“We remain steadfast in our goal to introduce a much-needed new therapeutic option for the [United States] PV community, fostering more modern approaches to care that can help reduce the risk of disease progression,” Manning concluded.

_References

_{1. Pharmaessentia Resubmits Application to the US FDA for Ropeginterferon alfa-2b-njft to Treat Polycythemia Vera (PV). News release. PharmaEssentia Corporation. May 14, 2021. Accessed May 21, 2021. https://bit.ly/2SkrTI8}

_{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}