Protagonist Therapeutics (NASDAQ: PTGX) ("Protagonist" or "the Company") today presented updated data from two ongoing Phase 2 studies evaluating rusfertide in patients with polycythemia vera (PV), demonstrating its ability to essentially eliminate the need for phlebotomies in patients.Protagonist Therapeutics (NASDAQ:PTGX) (“Protagonist” or “the Company”) today presented updated data from two ongoing Phase 2 studies evaluating rusfertide in patients with polycythemia vera (PV), demonstrating its ability to essentially eliminate the need for phlebotomies in patients. Rusfertide also showed rapid and sustained hematocrit control in patients requiring frequent phlebotomies or those having high baseline hematocrit levels (>48%). The data were presented in two oral presentations at the American Society of Hematology (ASH) 2021 Annual Meeting, in addition to the Company’s three poster presentations: one describing the Phase 3 study design for rusfertide in PV; one presenting pre-clinical findings with a hepcidin analog in a mouse model of PV; and another poster on the Phase 2 clinical proof-of-concept data for rusfertide in hereditary hemochromatosis (HH).
“The latest data continues to demonstrate rusfertide’s potential to maintain rapid and durable control of hematocrit and essentially eliminate the need for phlebotomies in phlebotomy-dependent PV patients, while offering meaningful improvements across various quality of life measures,” said Ronald Hoffman, MD, Director of the Myeloproliferative Disorders Research Program at the Icahn School of Medicine at Mount Sinai, and principal investigator for the study. “Early findings for rusfertide induction therapy also demonstrate its ability to rapidly control hematocrit in patients with elevated hematocrit levels above 48 percent, and to sustain those effects in maintenance, highlighting rusfertide’s potential efficacy in a wider spectrum of PV patients.”
“We are extremely encouraged by the totality and consistency of the positive results presented today at ASH for rusfertide in polycythemia vera, and by the support we are garnering from the physician community as we continue to execute against our goal of addressing unmet medical needs through this natural hormone mimetic therapy,” said Dinesh V. Patel, PhD, President and Chief Executive Officer of Protagonist. “The upcoming double-blinded, placebo-controlled Phase 3 PV study is a transformative step in the progressive journey of rusfertide, from de novo discovery to a registrational study. In addition, we look forward to providing clarity on our next steps in HH and other iron-overload related diseases in 2022, thereby expanding the potential utility of rusfertide into multiple indications.”
Summary of Key Results
Updated Results from Phase 2 Study Evaluating Rusfertide in Patients with PV
In this Phase 2 study, 63 phlebotomy-dependent PV patients were treated with rusfertide for up to 18 months. The results of the study demonstrated the essential elimination of the need for therapeutic phlebotomy (TP). Rapid, sustained, and durable control of hematocrit levels below 45% was observed without a significant increase in white blood cell numbers or PV-related thromboses. During the first 28 weeks on treatment, 84% of patients required no phlebotomies, 14% required one, and 2% required two phlebotomies. The most frequent adverse events were injection site reactions which were transient in nature. Importantly, none of the treated PV patients suffered from thrombotic events. Serious and Grade 3-4 events were limited in number, less than 10 at the time of data cut-off. Two SAEs were previously reported as possible related to study drug.
Among patient reported outcomes, a third of the patients in the study also saw at least a 40% reduction in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Scores (MPN-SAF-TSS) from baseline at week 28. Sixty-nine percent of patients reported improvement in Patient Global Impression of Change from baseline at week 8.
New Results from Phase 2 Study Evaluating Rusfertide as an Induction Therapy in Patients with PV
In this Phase 2 study, induction therapy with twice weekly rusfertide was administered alone to patients with confirmed high hematocrit levels above 48%. In all 16 erythrocytotic PV patients, rusfertide demonstrated rapid reduction of hematocrit below 45% within weeks, without the need for TP. The drug was well tolerated. Post-induction, weekly rusfertide treatment maintained hematocrit levels without the need for TP. While this study remains ongoing, most reported drug related adverse events to date were grade 1-2, with injection site reactions being the most common adverse event.
Additional Poster Presentations
The design of Protagonist’s planned three-part, multicenter, global, double-blinded, placebo-controlled Phase 3 clinical trial was presented in a poster. This Phase 3 study is expected to commence in Q1 2022 and will evaluate rusfertide in patients with PV compared to placebo when added onto current therapy. The primary endpoint of the study will be the absence of phlebotomy during weeks 20-32 for patients on rusfertide.
Also presented in a poster were results from a pre-clinical study demonstrating that a rusfertide peptide analog reduced erythrocytosis by restricting iron needed for red blood cell production while normalizing body iron distribution in a murine model with JAK2-V617F mutations. These effects support the use of a hepcidin mimetic, such as rusfertide, for potential utility in PV through dose titration treatment to maintain hematocrit below 45%.
Results from a Phase 2a proof-of-concept study evaluating rusfertide in patients with HH were also presented in a poster, demonstrating that rusfertide reduced serum iron and maintained transferrin saturation below 45% with corresponding significant reductions in phlebotomies. Liver iron concentration measured by MRI were also maintained at pre-study levels in patients at the end of the six-month study. Rusfertide was generally well tolerated in patients with HH, with the most common adverse events being injection site reactions that were mild or moderate.
Details for ASH 2021 presentations are as follows:
Oral Presentations
Title: “Rusfertide (PTG-300) Controls Hematocrit Levels and Essentially Eliminates Phlebotomy Requirement in Polycythemia Vera Patients”
Session Title: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Novel Therapies for MPNs and JAK inhibitors for Myelofibrosis
Authors: Ronald Hoffman, MD, et al.
Title: “Rusfertide (PTG-300) Induction Therapy Rapidly Achieves Hematocrit Control in Polycythemia Vera Patients without the Need for Therapeutic Phlebotomy”
Session Title: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Novel Therapies for MPNs and JAK inhibitors for Myelofibrosis
Authors: Yelena Ginzburg, MD, et al.
Posters
Title: “A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300) in Patients with Polycythemia Vera”
Session Title: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Authors: Srdan Verstovsek, MD, PhD, et al.
Title: “Regulation of Iron Homeostasis and Efficacy of Rusfertide Analog Peptide in a Mouse Model for Polycythemia Vera”
Session Title: 102. Iron Homeostasis and Biology: Poster II
Authors: Roopa Taranath, PhD, et al.
Title: “Rusfertide (PTG-300), a Hepcidin Mimetic, Maintains Liver Iron Concentration in the Absence of Phlebotomies in Patients with Hereditary Hemochromatosis”
Session Title: 102. Iron Homeostasis and Biology: Poster I
Authors: Kris V. Kowdley, MD, et al.
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