Mimrylo (rusfertide) / Protagonist Therap, Takeda - LARVOL DELTA

Effect of Rusfertide on Cytoreductive Therapy Use in Patients With Phlebotomy-Dependent Polycythemia Vera: Post Hoc Analysis From the Randomized Controlled Phase 3 VERIFY Study (SOHO 2026) - P3 | "At baseline (randomization), 156/285 patients (54.7%) received CRT (hydroxyurea [HU], n = 109; interferon, n = 38; ruxolitinib, n = 7; other, n = 2), and 129 received PHL only. Analysis showed 41.7% of baseline CRT-treated PHL-dependent PV patients reduced or discontinued CRT during rusfertide exposure while maintaining hematocrit <45%, suggesting rusfertide may reduce PHL and/or CRT burden in patients with PV who have poorly controlled hematocrit."

Clinical • P3 data • Retrospective data • Oncology • Polycythemia Vera

Takeda’s Rusfertide (MIMRYLO) Included as Category 1 Treatment for Polycythemia Vera in National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms (Takeda Press Release) - "NCCN Guidelines inclusion was based on two late-stage pivotal studies that included over 360 patients with PV, showing that MIMRYLO met key efficacy endpoints and demonstrated a favorable safety profile. These studies included the Phase 3 global randomized VERIFY study (NCT05210790), as well as the Phase 2 REVIVE study (NCT04057040)."

NCCN guideline • Myeloproliferative Neoplasm

Ferritin Normalization Is Not Disease Control in HFE-Related Hemochromatosis: Residual Risk, Transferrin Saturation, and the Hepcidin-Ferroportin Axis. (PubMed, Eur J Haematol) - "It further explores novel hepcidin-ferroportin axis targeted treatments, including the hepcidin mimetic rusfertide, the oral ferroportin inhibitor vamifeport, and agents targeting TMPRSS6. Crucially, it highlights that these agents are still investigational and acknowledges that not all persistent morbidity in p.C282Y homozygotes stems from iron deposition. Nevertheless, the combination of high treatment burden, circulating iron toxicity unmeasured by ferritin, and continued tissue and organ risk post-ferritin normalization indicates that disease management in HFE-related hemochromatosis must look beyond ferritin alone, supporting the need for clinical trials to evaluate disease-targeted interventions rigorously."

Journal • Review • Diabetes • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology • TMPRSS6

Onco360, the nation’s leading independent Specialty Pharmacy, has been selected by Takeda Pharmaceuticals as an ultra-narrow limited distribution partner for MIMRYLO (rusfertide), which is indicated for the treatment of erythrocytosis in adults with polycythemia vera (PV) (GlobeNewswire)

Commercial • Polycythemia Vera

Protagonist Therapeutics Announces $300 Million Share Repurchase Program (ACCESS Newswire) - "The Company intends to fund the share repurchases from its cash, cash equivalents, and marketable securities, and from royalties and other payments received under the Company's collaboration arrangements with Takeda related to MIMRYLO (rusfertide) and with Johnson & Johnson related to ICOTYDE (icotrokinra)....The Company expects to receive the payments from Takeda in the fourth quarter of 2026."

Commercial • Plaque Psoriasis • Polycythemia Vera

Rusfertide (Ptg-300) Treatment Interruption Reverses Hematological Gains and Upon Reinitiation, Restoration of Clinical Benefit Observed in Patients With Polycythemia Vera (SOHO 2022) - P2, P3 | "Rusfertide maintains HCT at <45%, essentially eliminates TP requirements, and reverses iron defi ciency in PV patients with/without cytoreductive agents. Reversal of hematological parameters during dosing interruption further confi rms the effect of rusfertide on erythrocytosis and iron homeostasis. A global Phase 3 trial, VERIFY (NCT05210790), has been initiated."

Clinical • Oncology • Polycythemia Vera

Subgroup Analysis of Adverse Events Following Rusfertide Dosing in Revive: A Phase 2 Study of Patients with Polycythemia Vera (ASH 2022) - P2 | "Consistent with previous reports [Pemmaraju, Blood 2019], secondary malignancies (6 early-stage skin cancers and 1 AML) were observed in 5 patients, all with prior history of malignancy or cytoreductive therapy. These data suggest that the rusfertide TEAE profile is manageable across the range of PV patients."

Adverse events • Clinical • P2 data • Acute Myelogenous Leukemia • Cardiovascular • Fatigue • Genetic Disorders • Hematological Disorders • Non-melanoma Skin Cancer • Polycythemia Vera • Pulmonary Disease • Skin Cancer • Solid Tumor • Thrombocytosis • Thrombosis

TARGETED THERAPY OF UNCONTROLLED ERYTHROCYTOSIS IN POLYCYTHEMIA VERA WITH THE HEPCIDIN MIMETIC, RUSFERTIDE: - BLINDED RANDOMIZED WITHDRAWAL RESULTS OF THE REVIVE STUDY (EHA 2023) - P2 | "The randomized withdrawal phase of the REVIVE study met its primary endpoint and demonstrated that rusfertide is a highly effective agent in patients with PV receiving TP with or without CYTO. Rusfertide is a novel hepcidin mimetic that selectively targets uncontrolled erythrocytosis in PV. Rusfertide is well tolerated and produces sustained and durable HCT control, obviating the need for TP in PV patients."

Clinical • Late-breaking abstract • Cardiovascular • Hematological Disorders • Polycythemia Vera

Durability of Hematocrit Control in Polycythemia Vera with the First-in-Class Hepcidin Mimetic Rusfertide: Two-Year Follow up Results from the Revive Study (ASH 2023) - P2 | "The REVIVE OLE demonstrated that rusfertide can provide long-term control of HCT, without phlebotomy, in patients with PV receiving TP with or without CYTO. Ferritin improved with rusfertide dosing and other lineages, after an initial increase in platelet counts both platelets and leucocyte counts remained stable during rusfertide treatment. Rusfertide was added to the current standard of care and was generally well-tolerated; most TEAEs were grade 1 or 2."

Cardiovascular • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera. (PubMed, N Engl J Med) - P2 | "In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.)."

Journal • Chronic Eosinophilic Leukemia • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

UPDATED LONG-TERM RESULTS FROM THE PHASE 2 REVIVE STUDY INVESTIGATING THE HEPCIDIN MIMETIC RUSFERTIDE IN POLYCYTHEMIA VERA PATIENTS (PTS): HEMATOCRIT CONTROL AND THERAPEUTIC PHLEBOTOMY (TP) FREQUENCY (EHA 2024) - P2, P3 | "In REVIVE, rusfertide added to TP with or without CRT provided long-term durable control of Hct anddecreased the need for TP compared with the pre-study period. REVIVE pts are eligible to roll over to the open-label phase 2 extension THRIVE study (NCT06033586), which will continue to assess the long-term safety andefficacy of rusfertide. The randomized phase 3 VERIFY study (NCT05210790) is also ongoing to evaluaterusfertide vs."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Dermatology • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Musculoskeletal Pain • Novel Coronavirus Disease • Oncology • Pain • Polycythemia Vera • Pruritus

Final Results from the Phase 2 Revive Study Investigating the Hepcidin Mimetic Rusfertide in Patients with Polycythemia Vera (PV) (ASH 2024) - P2, P3 | "Patients are eligible to roll over to the phase 2 THRIVE OLE study (NCT06033586), which will continue to assess the long-term safety and efficacy of rusfertide for a total period of up to 5.8 years. The randomized phase 3 VERIFY study (NCT05210790) is ongoing and will evaluate rusfertide vs placebo in PV patients."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Dermatology • Fatigue • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Musculoskeletal Pain • Myeloproliferative Neoplasm • Oncology • Pain • Polycythemia Vera • Pruritus • Skin Cancer • CRP • IL6

Results from VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV). (ASCO 2025) - P3 | "In pts with PV receiving SOC, rusfertide resulted in a statistically significant reduction in the mean number of PHLs and improved Hct control. Rusfertide is the first investigational agent to target the hepcidin pathway to control Hct and the first agent to prospectively demonstrate a statistically significant improvement in the PROMIS Fatigue SF-8a and MFSAF PROs in pts with PV. Rusfertide had a safety and tolerability profile consistent with rusfertide in prior studies."

Clinical • Late-breaking abstract • P3 data • Anemia • Fatigue • Polycythemia Vera

Long-term rusfertide treatment in polycythemia vera: Initial results from the phase 2 THRIVE extension study (ASH 2025) - P2, P3 | "After transitioning to THRIVE, continued treatment with rusfertide with or without CRTdemonstrated consistent, long-term Hct control with reduced therapeutic PHLs compared to baseline.With a median of 3.8 years of treatment, rusfertide's safety profile was consistent with priorobservations.Support: Protagonist Therapeutics, Inc."

P2 data • Basal Cell Carcinoma • Bladder Cancer • Dermatology • Genito-urinary Cancer • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Musculoskeletal Pain • Non-melanoma Skin Cancer • Polycythemia Vera • Pruritus • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma

Rusfertide or placebo plus current standard-of-care therapy for polycythemia vera: Durability of response and safety results through week 52 from the randomized controlled phase 3 VERIFY study (ASH 2025) - P3 | "Rusfertide met the primary and all 4 key secondary endpoints in VERIFY and continued toprovide durable, sustained control of Hct <45% and a relative absence of PHL up to Wk 52. This benefitwas maintained across all subgroups, including age, PV risk category, and ongoing CRT. Similar findingswere also observed after pts crossed over from PBO to rusfertide."

Clinical • P3 data • Polycythemia Vera

IMPACT OF RUSFERTIDE ON POLYCYTHEMIA VERA (PV)-RELATED SYMPTOMS AND PATIENT-REPORTED OUTCOME-RELATED ITEMS IN THE RANDOMIZED, DOUBLE-BLIND PHASE 3 VERIFY STUDY (EHA 2026) - P3 | "Although items improved in the PBO arm, numerically greater improvements in all items were observed in the rusfertide arm. These findings support the key PRO-focused secondary endpoints in VERIFY, further demonstrating that rusfertide broadly improved symptomatology- related items in pts with PV."

Clinical • P3 data • Patient reported outcomes • Chronic Eosinophilic Leukemia • Hematological Disorders • Hematological Malignancies • Musculoskeletal Pain • Myeloproliferative Neoplasm • Polycythemia Vera

THROMBOEMBOLIC AND PROGRESSION EVENTS IN PHLEBOTOMY-DEPENDENT PATIENTS WITH POLYCYTHEMIA VERA (PV): LONG-TERM RESULTS FROM THE PHASE 2 REVIVE AND THRIVE OPEN-LABEL EXTENSION RUSFERTIDE STUDIES (EHA 2026) - P2, P3 | "All 7 pts with on-study TE(s) had prior risk factors (eg, hypertension) and high-risk PV (4 had TE[s] prior to study entry, including 3 venous, and 2 arterial events), and 4 received hydroxyurea at study entry. Two pts (2.8%) had a post-PV progression event. Long-term follow-up will continue to further investigate TEs and other events following rusfertide exposure."

Clinical • P2 data • Acute Myelogenous Leukemia • Cerebral Hemorrhage • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Myocardial Infarction • Polycythemia Vera • Pulmonary Embolism • Respiratory Diseases

Modulation of the Hepcidin Pathway Produces Homogeneous Erythropoietic Suppression but Heterogeneous Iron Repletion in Polycythemia Vera: Lessons From REVIVE and IMPRSSION (SOHO 2026) - "Agents under clinical investigation harness the hepcidin pathway to restrict iron, resulting in a "chemical phlebotomy." Rusfertide, a hepcidin mimetic, and sapablursen, a transmembrane protease serine 6 (TMPRSS6) antisense oligonucleotide that leads to increased endogenous hepcidin production, are two such emerging therapies. We showed that control of HCT is linked to an increase in ferritin when two mechanistically distinct agents modulating the hepcidin-iron axis suppress erythropoiesis in PV. Although interpatient variability in HCT was narrow, increases in ferritin levels were more heterogenous. Hence, HCT response does not reliably predict iron repletion status."

Heterogeneity • Oncology • Polycythemia Vera • TMPRSS6

Benefit of Rusfertide Maintained in Patients With Low-Risk or High-Risk Polycythemia Vera: Efficacy and Safety Subgroup Analysis From the Randomized Controlled Phase 3 VERIFY Study (SOHO 2026) - P3 | "Rusfertide benefit was maintained for clinical response and all four key secondary endpoints vs PBO irrespective of baseline risk group."

Clinical • P3 data • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Royalty Pharma…announced an agreement for $100 million in funding to Zealand Pharma in exchange for Zealand Pharma’s economics related to rusfertide (PTG-300), a potential first-in-class therapy for polycythemia vera (GlobeNewswire) - "Under the terms of the royalty purchase and sale agreement, Royalty Pharma will provide $100 million to Zealand Pharma in exchange for its economic interests related to rusfertide, including rights to a 1% royalty on potential future global net sales of rusfertide and regulatory and commercial milestones. This consists of $50 million upon closing of the transaction with the remaining $50 million due upon the first anniversary of the closing of the agreement. Zealand Pharma will retain the right to a 0.25% royalty on annual net global sales of rusfertide greater than $1.5 billion, while Royalty Pharma will retain a 0.75% royalty on sales above $1.5 billion."

Financing • Polycythemia Vera

A Study of Rusfertide in Adults With Polycythemia Vera in China (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Takeda

New P2 trial • Polycythemia Vera

Takeda Receives U.S. FDA Approval of MIMRYLO (rusfertide), Marking a Potential Shift in the Treatment Paradigm for Polycythemia Vera (Takeda Press Release) - "The approval was supported by data from the global randomized Phase 3 VERIFY study (NCT05210790) that included 293 patients with PV, showing that MIMRYLO met all efficacy endpoints and demonstrated a favorable safety profile....The open-label extension of the VERIFY trial is ongoing and Takeda will share further findings at upcoming medical conferences."

FDA approval • P3 data • Polycythemia Vera

Targeting the hepcidin-ferroportin axis in polycythemia vera: a complementary approach to clone-directed therapies. (PubMed, Blood Rev) - "The hepcidin mimetic rusfertide has shown durable hematocrit control and marked reduction of phlebotomy requirements across phase 2 and phase 3 studies, with predictable changes in systemic iron markers...Within this framework, iron metabolism can be viewed as a downstream, regulatable determinant of erythropoietic output, distinct from but integrated with clonal and inflammatory signaling. This review summarizes biological and clinical evidence on iron homeostasis in PV, focusing on the hepcidin-ferroportin axis and its integration with clone-directed therapies."

Journal • Review • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Second Quarter 2026 Recent Developments and Upcoming Milestones: Rusfertide (ACCESS Newswire) - "As announced on March 2nd, the NDA for rusfertide was accepted by the FDA and granted Priority Review in Q1 2026, with a PDUFA goal date in August 2026."

PDUFA • Polycythemia Vera

Emerging agents and regimens for myeloproliferative neoplasms: updates from ASH 2025 Annual Meeting. (PubMed, Exp Hematol Oncol) - "At ASH 2025 Annual Meeting, multiple investigational strategies aimed to address these limitations, including clone-directed targeting (INCA033989), phlebotomy-sparing physiologic therapy (rusfertide), and epigenetic disease-modifying combinations (pelabresib). We summarized the latest updates on these emerging agents and regimens for MPNs from the 2025 ASH Annual Meeting."

Journal • Genetic Disorders • Hematological Disorders • Myeloproliferative Neoplasm • Oncology