The biologics license application seeking the approval of ropeginterferon alfa-2b-njft for use in the treatment of patients with polycythemia vera has been resubmitted to the FDA.
The biologics license application (BLA) seeking the approval of ropeginterferon alfa-2b-njft for use in the treatment of patients with polycythemia vera has been resubmitted to the FDA, according to an announcement from PharmaEssentia USA Corporation.1
The decision follows the issuance of a complete response letter in March 2021, in which the regulatory agency requested more data regarding the administration format of the product.2 No concerns about the clinical profile of the agent were raised. However, the agency also cited that the pre-approval inspection of the company’s manufacturing facility in Taiwan had been delayed due to restrictions caused by the ongoing COVID-19 pandemic.
“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,” Meredith Manning, US General Manager at PharmaEssentia USA Corporation, stated in a press release. “We remain steadfast in our goal to introduce a much-needed new therapeutic option for the US polycythemia vera community, fostering more modern approaches to care that can help reduce the risk of disease progression.”
Previously, in June 2020, the FDA accepted the BLA for ropeginterferon alfa-2b-njft for use in patients with polycythemia vera in the absence of symptomatic splenomegaly based on data from the phase 3 PROUD/CONTI-PV trial (NCT02218047). Study participants were given either the novel pegylated interferon (n = 95) or hydroxyurea/best available therapy (BAT; n = 74). At 36 months, ropeginterferon alfa-2b-njft elicited a higher complete hematological response rate of 70.4% vs 51.4% with hydroxyurea/BAT.3
Responses with ropeginterferon alfa-2b-njft were observed to steadily rise over the treatment course of 24 months and they were maintained after 36 months. Specifically, 66% of patients who were given ropeginterferon alfa-2b-njft achieved a molecular response after 36 months compared with 27% of patients who received hydroxyurea/BAT. Notably, the molecular responses achieved were closely related to complete hematological responses.
To be eligible for enrollment on the trial, patients needed to be 18 years of age or older and have early-stage polycythemia vera; they could not have a history of cytoreductive treatment or have previously received less than 3 years of hydroxyurea.
Participants were randomized 1:1 to receive either subcutaneous ropeginterferon alfa-2b-njft every 2 weeks, starting at a dose of 100 μg, or oral hydroxyurea given at a starting dose of 500 mg daily. After 1 year of treatment, participants were allowed to opt to enter the extension portion of the trial, CONTINUATION-PV.
The primary end point of PROUD-PV was noninferiority of ropeginterferon alfa-2b-njft vs hydroxyurea in terms of complete hematological response with normal spleen size at 12 months. The co-primary end points of CONTINUATION-PV were complete hematological response with normalization of spleen size and with improved disease burden.
Final data from PROUD-PV and findings from an interim analysis at 36 months of the CONTINUATION-PV trial were published in the Lancet Haematology.4 A total of 257 patients underwent randomization; 127 patients received treatment in both arms and 171 went on to the CONTINUATION-PV trial.
Data from PROUD-PV indicated that 21% of patients (n = 26/122) who received ropeginterferon alfa-2b-njft and 28% of those (n = 34/123) who received standard treatment met the composite primary end point of complete hematological response with normal spleen size.
In the extension trial, 53% of patients (n = 50/93) in the investigative arm and 38% of those (n = 28/74) of those in the control arm met the end point of complete hematological response and improved disease burden at 36 months (P = .044). Moreover, 43% (n = 53/123) of those in the investigative arm achieved complete hematological response without the spleen criterion vs 46% (n = 57/125) of those in the control arm at 12 months in the PROUD-PV trial (P = .63); these rates were 71% (n = 67/95) and 51% (n = 38/74) at 36 months in the CONTINUATION-PV trial (P = .012).
The most commonly experienced grade 3 or 4 treatment-related toxicities with ropeginterferon alfa-2b-njft included increased γ-glutamyltransferase (6%) and increased alanine aminotransferase (3%); in the standard therapy group, they were leucopenia (5%) and thrombocytopenia (4%).
Serious treatment-related toxicities were reported in 2% of those in the investigative arm and 4% of those in the control arm. One treatment-related death occurred in the control arm; the patient died from acute leukemia.
Previously, ropeginterferon alfa-2b-njft received an orphan drug designation from the FDA for the treatment of patients with polycythemia vera. In 2019, the product was approved in Europe for this indication.