A Phase 3b, Single-Arm, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Ropeginterferon Alfa-2b-Njft (P1101) in Adult Patients with Polycythemia Vera

Introduction Polycythemia vera (PV), the most common chronic myeloproliferative neoplasm, is a long-term, debilitating, potentially life-threatening disease with limited treatment options. Most patients with PV receive therapeutic phlebotomy and low-dose aspirin to reduce blood viscosity. Cytoreductive therapy is also recommended for both high- and low-risk patients. Ropeginterferon alfa-2b-njft (P1101) is the first and only FDA-approved interferon for treating PV regardless of patients’ risk category or past treatment history. Clinical trial results confirm high complete hematologic response (CHR) rates and deep molecular responses, however, time to achieve CHR can take 6 months or longer because dose escalation to the highest maintenance dose ranged from 16 to 28 weeks. This single-arm, Phase 3b study of U.S. and Canadian patients seeks to confirm that a higher starting dose and faster dose escalation is safe, efficacious, and supportive of a new, optimized treatment regimen.

Materials & Methods The planned enrollment for this study is ≈64 adult patients with PV from the U.S. and Canada. Treatment-naïve patients and those pretreated with hydroxyurea (HU) will be included. The latter will undergo HU tapering by 25% every week for the first 4 weeks. Patients who received previous interferon or JAK inhibitor therapy will be excluded from the study. The primary efficacy endpoint is CHR at Week 24. A 72-week extension will evaluate long-term safety and efficacy, with secondary endpoints including time to CHR, proportion of patients in CHR at Weeks 12, 48, and 96; time to maintenance dose; and time to freedom from phlebotomies. CHR is defined as hematocrit <45%, white blood cell count ≤10 × 10⁹/L, platelets ≤400 × 10⁹/L in the absence of phlebotomy in the previous 12 weeks. P1101 will be provided in 500-mcg prefilled syringes for subcutaneous administration every 2 weeks, with a starting dose of 250 mcg (Day 0), 350 mcg (Week 2), and target optimal dose of 500 mcg (Week 4). Dose adjustments will be allowed if safety or tolerability concerns arise.

Results We anticipate this study's results to be in the range of the CHR response rates of the PROUD/CONTINUATION-PV study, but in a shorter period of time. The Phase 3, randomized, controlled, open-label trial conducted in 48 clinics in Europe showed that patients who received the maximum P1101 dose of 500 mcg earlier had better treatment responses than seen in slower-titrated patients. It is expected that the faster and simpler dosing scheme of 250-350-500 mcg, escalated every 2 weeks, will improve treatment compliance and tolerance and will allow patients achieve complete hematologic remissions significantly earlier than seen in the PROUD/CONTINUATION-PV study.

Conclusion This Phase 3b study of P1101 will provide support for an amended dosing regimen that can achieve a more rapid CHR and optimize treatment of PV.

Mascarenhas:Janseen: Research Funding; AbbVie: Consultancy, Research Funding; Forbius: Research Funding; Galecto: Consultancy; PharmaEssentia: Consultancy, Research Funding; Prelude Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merus: Research Funding; Merck: Research Funding; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Consultancy; Kartos: Consultancy, Research Funding; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy; Sierra Oncology: Consultancy; CTI BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Imago: Consultancy; Roche: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Zagrijtschuk:PharmaEssentia: Current Employment. Zimmerman:PharmaEssentia: Current Employment. Urbanski:PharmaEssentia: Current Employment.