Promedior Presents Positive Data from a Phase 2 Study of PRM-151 in Myelofibrosis Patients Failed/Ineligible for Ruxolitinib at the 24th European Hematology Association Annual Congress
- Category: Proteins and Peptides
- Published on Tuesday, 18 June 2019 11:57
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Efficacy and Safety Data Confirmed in a Population with High Unmet Need
LEXINGTON, MA, USA I June 17, 2019 I Promedior, Inc., a clinical stage biotechnology company developing novel therapeutics for the treatment of fibrosis, announced positive safety and efficacy data from a Phase 2 study of PRM-151 in myelofibrosis (MF) patients that either failed (76%) or were ineligible for Ruxolitinib. The study demonstrated clear evidence of biologic activity of PRM-151 in reducing bone marrow fibrosis in 28% of patients. PRM-151 was well tolerated throughout the 9 monthly cycles of therapy by this very sick population with high unmet need. The prognosis for myelofibrosis patients who fail Ruxolitinib is extremely poor with a median survival of only 6 months.1 The results were provided in an oral presentation at the 24th European Hematology Association (EHA) Annual Congress, which took place June 13-16, 2019 in Amsterdam. The EHA presentation follows the simultaneous publication in Lancet Respiratory Medicine and the presentation at the American Thoracic Society 2019 International Conference of positive safety and efficacy data from the Company's open-label extension study of PRM-151 in patients with Idiopathic Pulmonary Fibrosis (IPF).2 Together, the data underscore the profound clinical potential of PRM-151, a human recombinant form of pentraxin-2, to affect fibrosis and inflammation in both of these incurable diseases.
"There are very few options for patients that fail or cannot take Ruxolitinib. Longevity is impacted by platelet level and 59% of the patients in this trial had a platelet count of less than 50 x 109/L so these patients were very sick. The Phase 2 data demonstrates the promising antifibrotic activity of PRM-151 as measured by reduction in bone marrow fibrosis and improvement in hematologic measures," said Dr. Srdan Verstovsek, Professor, Leukemia Department, MD Anderson Cancer Center. "Patients also showed a reduction in their myeloproliferative neoplasm symptoms, as well as a trend to prolonged survival with PRM-151 monotherapy in these refractory MF patients with great unmet need."
The Phase 2 MF clinical trial was a randomized, double blind, study to determine the efficacy and safety of three different doses of PRM-151 in subjects with Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (post-PV MF), or Post-Essential Thrombocythemia MF (post-ET MF). Subjects were randomized to one of three dose cohorts: 0.3 mg/kg, 3.0 mg/kg or 10 mg/kg of PRM-151 administered once-a-month. The primary endpoint was bone marrow response rate, defined as the percent of subjects with a reduction in bone marrow fibrosis score by at least one grade (according to WHO criteria) at any time during the study. The oral presentation at EHA reported efficacy and safety data from 97 MF patients treated with PRM-151 monotherapy. Decreases in bone marrow fibrosis (BMF) and collagen grade were observed in approximately 30% of patients across all dose levels. Increases in hemoglobin levels and platelet counts, as well as reductions in transfusion requirements were also reported across all doses. Improvements in symptoms and spleen volume were observed in 40 to 50% of patients. Low platelet count correlates with mortality and 62% of the patients showed a 50% or greater reduction in platelet transfusions.3 The 10 mg/kg dose resulted in clinical benefit in a patient population with the most advanced disease, including a trend towards survival benefit.
This data together with the data in IPF, underscores the clinical potential for human recombinant pentraxin-2, an endogenous regulatory protein modulating fibrosis and inflammation, is very significant. The Company looks forward to advancing the clinical program for PRM-151 in both MF and IPF, and will explore other fibrotic indications in the future.
Myelofibrosis (MF), a type of myeloproliferative neoplasm, is a serious, life-limiting cancer that is characterized by fibrosis of the bone marrow. Replacement of the bone marrow by scar tissue prevents the normal production of blood cells, leading to anemia, fatigue, and increased risk of bleeding and infection. Production of blood cells shifts to the spleen and liver (extramedullary hematopoiesis), which become enlarged, causing severe discomfort, inability to eat, and weakness. Symptomatic myelofibrosis affects approximately 18,000 people per year in the US, with a median age of 61-66.4 The only potentially curative treatment is allogeneic bone marrow transplant, which results in reversal of fibrosis and all symptoms, but is a realistic option for only a small number of patients. Other currently available therapies address the symptoms but have minimal if any impact on the underlying fibrosis.
PRM-151, Promedior's lead product candidate, is a recombinant form of the endogenous human innate immunity protein pentraxin-2 (PTX-2), which is specifically active at the site of tissue damage. PRM-151 is an agonist that acts as a macrophage polarization factor to prevent and potentially reverse fibrosis. PRM-151 has shown broad anti-fibrotic activity in multiple preclinical models of fibrotic disease, including pulmonary fibrosis, myelofibrosis5, acute and chronic nephropathy, liver fibrosis, and age-related macular degeneration. In addition to the randomized Phase 2 study in IPF published in JAMA in 20186, Phase 1a and 1b clinical studies in healthy subjects and IPF patients have demonstrated that PRM-151 was well-tolerated.
Promedior is a clinical stage biotechnology company pioneering the development of targeted therapeutics to treat diseases involving fibrosis. Fibrosis is a harmful process that occurs in many diseases, when normal healthy tissue is replaced with excessive scar tissue, compromising function and ultimately leading to organ failure. Promedior's proprietary platform is based upon pentraxin-2, an endogenous human protein that is specifically active at the site of tissue damage, preventing and potentially reversing fibrosis.
Promedior has successfully advanced its lead therapeutic candidate in human clinical trials and is initially focused on rare fibrotic diseases, including idiopathic pulmonary fibrosis and myelofibrosis. Promedior is backed by leading global healthcare venture investors and has a significant intellectual property estate relating to the discoveries and applications of pentraxin-2 therapeutics.
Additional information is available at www.promedior.com.
1 Jabbour, Elias et al. "Outcome Of Patients (pts) With Myelofibrosis (MF) After Ruxolutinib (Rux) Therapy." Blood Journal. Blood 2013 122:1584; http://www.bloodjournal.org/content/122/21/1584?sso-checked=true
2 Raghu G, van den Blink B, Hamblin MJ et al. "Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study." Lancet Respir Med. 2019; (published online May 20.) http://dx.doi.org/10.1016/S2213-2600(19)30172-9
3 Masarova, L et al. "Significance of thrombocytopenia in patients with primary and postessential thrombocythemia/polycythemia vera myelofibrosis." 2018 Mar;100(3):257-263. doi: 10.1111/ejh.13005. Epub 2018 Jan 17. https://www.ncbi.nlm.nih.gov/pubmed/29226426
4 Mehta, J. et al. 2014. "Epidemiology of myeloproliferative neoplasms in the United States", Leukemia & Lymphoma. 55:595-600
5 Verstovsek, S. et al. 2016. Role of neoplastic monocyte derived fibrocytes in primary myelofibrosis. J. Exp. Med. 213:1723-1740.
6 Raghu G, van den Blink B, Hamblin MJ, et al. Effect of recombinant human pentraxin 2 vs placebo on change in forced vital capacity in patients with idiopathic pulmonary fibrosis: a randomized clinical trial [published online May 20, 2018]. JAMA. doi:10.1001/jama.2018.6129