Ropeginterferon Alfa-2b Proves to be Efficacious, Safe in Japanese Patients with Polycythemia Vera

Ropeginterferon alfa-2b-njft (Besremi) produced durable complete hematologic responses (CHRs) without phlebotomy and showcased a consistent safety profile in Japanese patients with polycythemia vera, according to findings from a phase 2 study (NCT04182100) presented during the 2022 EHA Congress.¹

The agent induced a CHR rate of 27.6% (95% CI, 12.7%-47.2%) in the intention-to-treat (ITT) population (n = 29), with a median time to CHR of 52.0 weeks (95% CI, 24.1- 52.3).

Notably, the CHR was comparable, irrespective of prior use of hydroxyurea (Hydrea). In those who did not receive prior hydroxyurea (n = 14), the CHR rate was 35.7% (95% CI, 12.8%-64.9%) vs 20% (95% CI, 4.3%-48.1%) in those who did (n = 15). Moreover, response rates were also similar by age, with patients under 60 years (n = 22) experiencing a CHR rate of 27.3% (95% CI, 10.7%-50.2%) vs 28.6% (95% CI, 3.7%-71.0%) in those aged 60 years or older (n = 7).

“Overall, outcomes were similar to those of previous phase 3 studies [evaluating ropeginterferon alfa-2b],” Keita Kirito, MD, PhD, lead study author and associate professor in the Department of Hematology and Oncology at the University of Yamanashi in Japan, and colleagues, wrote in a poster presentation of the data.

Because of the favorable pharmacokinetic properties of ropeginterferon alfa-2b, the agent can be administered less frequently with strong tolerability. In November 2021, the FDA approved ropeginterferon alfa-2b for use in patients with polycythemia vera, based on findings from the phase 1/2 PEGINVERA (NCT01193699) and phase 3 PROUD/CONTINUATION-PV (NCT02218047) studies.² The agent has also been approved for the treatment of patients with polycythemia vera without symptomatic splenomegaly in Europe, Taiwan, and South Korea.

The safety and efficacy of ropeginterferon alfa-2b had not been evaluated in Japanese patients with polycythemia vera. To address this need, investigators launched the open-label, multicenter, single-arm, phase 2 study, in which they sought to examine the clinical utility of the agent in this patient population.

The trial included Japanese adults with polycythemia vera, including young patients and those with low thrombosis risk for whom guideline-based standard-of-care treatments were difficult to apply. Patients were required to have a diagnosis of polycythemia vera according to the World Health Organization 2008/2016 criteria, less than 3 years of cumulative prior treatment with hydroxyurea, and adequate hepatic function.

Those who were naïve to cytoreduction needed to have 1 of the following: at least 1 documented major cardiovascular polycythemia vera–related event, poor tolerance of phlebotomy or frequent need of phlebotomy, a platelet count higher than 1000 x 10⁹/L or a white blood cell count above 10 x 10⁹/L at 2 measurements within 1 month prior to the start of study treatment, or the manifestation of disease-related signs and symptoms.

Patients were excluded from the study if they presented with symptomatic splenomegaly, previously used or had contraindications to interferon alfa, had a documented history of resistance to hydroxyurea, had circulating blasts in the peripheral blood within 3 months of study enrollment, or had any serious clinical condition that could affect study participation or patient safety.

Study participants received subcutaneous ropeginterferon alfa-2b once every 2 weeks for 12 months. Doses started at 100 μg (or 50 μg for patients already receiving hydroxyurea) and increased by 50 μg per visit, up to 500 μg. All patients also received 75 mg to 150 mg of aspirin per day or another prophylactic antithrombotic agent.

Phlebotomy-free CHR at weeks 36 and 52 served as the primary end point of the trial. CHR was defined as a hematocrit level of less than 45%, as well as normalization of white blood cell count, defined as below 10 x 10⁹/L, and a platelet count that was no higher than 400 x 10⁶/L.

Of 32 patients assessed for eligibility, 29 patients were assigned to treatment. Two patients discontinued treatment; 1 did so because of a treatment-emergent adverse effect (TEAE) in the form of silent thyroiditis and 1 withdrew consent. Twenty-seven patients completed study treatment and advanced to the extension study. At the end of study treatment, 14 patients were receiving the maximum 500-μg dose of ropeginterferon alfa-2b.

In the ITT population (n = 29), the median age was 54 years (range, 26-72) and 55.2% of patients were female; 75.9% of patients were younger than 60 years. All patients had an ECOG performance status of 0, and 51.7% of patients had prior treatment with hydroxyurea. Moreover, 93.1% of patients presented with a JAK2 V617F mutation (93.1%), and 72.4% used aspirin. At baseline, the mean hematocrit was 46.85%, the mean platelet count was 747.3 x 10⁹/L, and the mean leukocyte count was 17.07 x 10⁹/L.

Additional data showed that after patients presented with a median JAK2 V617F allele burden of 81.8 (range, 23.6-98.3) at baseline, that was reduced to 52.5 (range, 6.2-92.0) at week 52. Hematocrit, platelets, and white blood cells also decreased over time, with their mean values reaching their respective target ranges.

Moreover, at baseline, 27.6% of patients required phlebotomies at baseline. By week 52, only 1 patient required a phlebotomy.

TEAEs of any grade that were related to ropeginterferon alfa-2b were experienced by all patients, although no grade 3 or higher TEAEs were reported. One serious TEAE of gastroenteritis occurred, but this was not found to be related to study treatment. Moreover, 69% of patients experienced a grade 1 TEAE, and 31% experienced a grade 2 TEAE.

The TEAEs of any grade reported with ropeginterferon alfa-2b in 10% or more of patients included alopecia (55.2%), fatigue (27.6%), influenza-like illness (27.6%), increased alanine aminotransferase (20.7%), increased beta 2 microglobulin (20.7%), increased aspartate aminotransferase (17.2%), diarrhea (17.2%), abnormal liver function test (13.8%), myalgia (13.8%), pyrexia (13.8%), anemia (10.3%), arthralgia (10.3%), increased gamma-glutamyl transferase (10.3%), injection site reaction (10.3%), and malaise (10.3%).

TEAEs of special interest included hypothyroidism (6.9%), silent thyroiditis (3.4%), anxiety (3.4%), and retinal hemorrhage (3.4%).

References

1. Kirito K, Edahiro Y, Ohishi K, et al. Phase 2, open-label, multicenter, single-arm study investigating the efficacy and safety of ropeginterferon alfa-2b in Japanese patients with polycythemia vera. Presented at: 2022 EHA Congress; June 9-12, 202; Vienna, Austria. Poster P1007
2. 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 July 12, 2022. https://bwnews.pr/3nbXCYO