Ropeginterferon alfa-2b-NJFT

BURLINGTON, Mass.--(BUSINESS WIRE)--PharmaEssentia Corporation (TWSE: 6446), a global biopharmaceutical company headquartered in Taiwan with deep expertise in the development of novel biologics for hematology and oncology, and its Japanese subsidiary today announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved the inclusion of a high-dose dosing regimen for Ropeginterferon alfa-2b in the product label as an alternative dosing schedule. Clinical data show that the high-dose regimen shortens the time to reach the target maintenance dose and supports earlier therapeutic benefit. The revision is based on the domestic Phase III A23-301 trial, an open-label, uncontrolled study in Japanese patients with polycythemia vera. Treatment was initiated at 250 mcg and, if tolerated, escalated to 350 mcg at two weeks and 500 mcg at four weeks, followed by subcutaneous administration every two weeks for up to 24 weeks. The Week 24 complete hematologic response rate was 57.1%. This approval was supported by compelling complete hematologic response (CHR) results achieved with a one-month optimized dosing regimen, enabling patients to reach the target 500 mcg dose significantly faster than in the previously approved bridging study, which required gradual titration over four to four and a half months. Importantly, the safety profile, including serious adverse events (SAEs), remained consistent with prior experience and comparable across dosing approaches. By allowing patients to achieve optimal therapeutic dosing more rapidly without compromising tolerability, this approval represents an important advancement in care. BESREMi® was approved in Japan in March 2023 for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of existing therapies. Under the previously recommended dosing schedule, treatment begins at 100 mcg, with 50 mcg increases every two weeks up to a maximum of 500 mcg. Under the new dosing regimen, patients receiving BESREMi® can reach the clinical maintenance dose more quickly than under the previous dosing regimen, supporting earlier disease control. “We are grateful to the Japanese regulatory authorities for their recognition of the clinical value of the high-dose regimen,” said Ko-Chung Lin, Ph.D., Founder and Chief Executive Officer of PharmaEssentia. “This approval reflects our commitment to optimizing treatment strategies for patients. We are confident in the clinical and commercial potential of the high-dose regimen and will continue to benefit more patients with PV worldwide.” About PharmaEssentia PharmaEssentia USA Corporation, located in Burlington, Massachusetts, is a subsidiary of PharmaEssentia Corporation (TWSE: 6446). PharmaEssentia Corporation, headquartered in Taipei, Taiwan, is a global and rapidly growing biopharmaceutical innovator and the developer and owner of BESREMi® (ropeginterferon alfa-2b-njft). Leveraging deep expertise and proven scientific principles, PharmaEssentia aims to deliver effective new biologics for challenging diseases in the areas of hematology, oncology, and immunology with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today PharmaEssentia is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung, Taiwan. For more information about PharmaEssentia USA, visit the website, LinkedIn or X (formerly Twitter). About BESREMi® (ropeginterferon alfa-2b-njft) Ropeginterferon alfa-2b-njft is currently FDA-approved and marketed as BESREMi® for the treatment of adults with polycythemia vera (PV). The Company is seeking a ropeginterferon alfa-2b-njft label expansion to include ET and has submitted a sBLA with the U.S. FDA. BESREMi® holds orphan drug designation in the United States for the treatment of polycythemia vera (PV) in adults. It has received regulatory approval in over 40 countries, including from the European Medicines Agency (2019), the U.S. Food and Drug Administration (2021), and the Pharmaceuticals and Medical Devices Agency in Japan (2023). The product was developed by PharmaEssentia. PharmaEssentia retains full global intellectual property rights across all indications. INDICATION BESREMi® is indicated for the treatment of adults with polycythemia vera. IMPORTANT SAFETY INFORMATION WARNING: RISK OF SERIOUS DISORDERS Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy. CONTRAINDICATIONS Existence of or history of severe depression, suicidal ideation, or suicide attempt Hypersensitivity to interferons or any inactive ingredients Moderate or severe hepatic impairment History or presence of active serious or untreated autoimmune disease History of transplantation and receiving immunosuppressant agents WARNINGS AND PRECAUTIONS Patients exhibiting the following events should be closely monitored and may require dose reduction or discontinuation of therapy: Depression and Suicide: Monitor closely for symptoms and need for treatment. Endocrine Toxicity: Discontinue if endocrine disorders occur that cannot be medically managed. Cardiovascular Toxicity: Avoid use in patients with severe, acute or unstable cardiovascular disease. Monitor patients with history of cardiovascular disorders more frequently. Decreased Peripheral Blood Counts: Perform blood counts at baseline, every 2 weeks during titration, and at least every 3-6 months during maintenance treatment. Hypersensitivity Reactions: Stop treatment and immediately manage reaction. Pancreatitis: Consider discontinuation if confirmed pancreatitis Colitis: Discontinue if signs or symptoms of colitis Pulmonary Toxicity: Discontinue if pulmonary infiltrates or pulmonary function impairment Ophthalmologic Toxicity: Advise patients to have eye examinations before and during treatment. Evaluate eye symptoms promptly and discontinue if new or worsening eye disorders. Hyperlipidemia: Monitor serum triglycerides before BESREMi ® treatment and intermittently during therapy and manage when elevated. Hepatotoxicity: Monitor liver enzymes and hepatic function at baseline and during treatment. Reduce dose or discontinue depending on severity. Renal Toxicity: Monitor serum creatinine at baseline and during therapy. Discontinue if severe renal impairment develops. Dental and Periodontal Toxicity: Advise patients on good oral hygiene and to have regular dental examinations. Dermatologic Toxicity: Consider discontinuing if clinically significant dermatologic toxicity. Driving and Operating Machinery: Advise patients to avoid driving or using machinery if they experience dizziness, somnolence, or hallucination. Please see full Prescribing Information, including Boxed Warning.

Japan’s Takeda Pharmaceutical (TSE: 4502 / NYSE: TAK) and partner California-based Protagonist Therapeutics, Inc. (NASDAQ: PTGX) announced an NDA filing with the US FDA for rusfertide, a first-in-class hepcidin mimetic peptide, for the treatment of adults with polycythemia vera (PV). With the filing granted Priority Review treatment, the Prescription Drug User Fee Act (PDUFA) target action date has been set for Q3 2026. The priority review award adds to previous grants of Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation for rusfertide. The VERIFY Study and Supporting Clinical Data for Rusfertide The NDA submission was primarily supported by the Phase III VERIFY study (NCT05210790), an ongoing three-part, global, randomized, placebo-controlled trial evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period. The VERIFY study rusfertide results showed that the drug met its primary endpoint — the proportion of patients achieving a response during Weeks 20–32, defined as the absence of phlebotomy eligibility — and all four key secondary endpoints. Phlebotomy eligibility in the trial required a confirmed hematocrit of 45% or higher that was at least 3 percentage points above baseline, or a hematocrit of 48% or higher. Patients receiving rusfertide plus current standard of care demonstrated a higher response rate compared to standard of care alone. The response encompassed hematocrit control, reduction in phlebotomy requirements, and improvement in patient-reported outcomes measuring fatigue and symptom burden. Through 52 weeks, the most common treatment-emergent adverse events among rusfertide-treated patients were injection site reactions (47.4%), anemia (25.6%), and fatigue (19.6%), predominantly grade 1 or 2. Serious adverse events occurred in 8.1% of rusfertide-treated patients overall. The NDA also incorporated four-year efficacy and safety data from the Phase II REVIVE study (NCT04057040), which enrolled 70 patients in dose-finding, 59 in a blinded randomized withdrawal portion, and 58 in an open-label expansion, as well as from the long-term extension THRIVE study (NCT06033586), which continues to follow 46 patients who transitioned from REVIVE. Rusfertide: the industry context Protagonist Therapeutics discovered rusfertide using its proprietary constrained peptide platform and led development from early-stage work through Phase III. In January 2024, Takeda and Protagonist entered into a worldwide license and collaboration agreement for rusfertide with Takeda leading global regulatory submissions. Protagonist retains an option to co-commercialize rusfertide in the US through a 50/50 profit-and-loss-share structure. PV is a myeloproliferative neoplasm characterized by erythrocytosis — the overproduction of red blood cells — which increases blood viscosity and elevates the risk of thrombotic events including stroke, deep vein thrombosis, and pulmonary embolism. The primary treatment goal is maintaining hematocrit below 45%. Current standard of care consists of therapeutic phlebotomy, low-dose aspirin, and cytoreductive agents such as hydroxyurea, pegylated interferon alfa, and ruxolitinib (Jakafi, Incyte). Ropeginterferon alfa-2b (Besremi, PharmaEssentia) received FDA approval in 2021 as the first interferon specifically indicated for PV regardless of treatment history. Despite these options, a substantial proportion of patients remain phlebotomy-dependent and continue to experience symptom burden including fatigue, pruritus, and night sweats. No therapy currently approved for PV treatment directly targets the hepcidin–ferroportin axis that governs iron-restricted erythropoiesis. Rusfertide occupies a distinct mechanistic position. As a synthetic hepcidin mimetic, it binds ferroportin (SLC40A1) and induces its internalization, restricting iron availability for red blood cell production. No other hepcidin mimetic has reached NDA stage in any indication. Several molecules targeting the same biological axis are in earlier-stage development, though these are being studied for iron-loading anemias instead of PV. Examples include Disc Medicine’s DISC-0974 (jatacimab), and CSL Vifor’s Vamifeport (VIT-2763), a small-molecule ferroportin inhibitor.