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FDA grants fast track designation to PRM-151 for myelofibrosis
The FDA granted fast track designation to PRM-151 as a potential treatment for patients with myelofibrosis, the drug’s manufacturer announced.
The designation encompasses three indications: primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
PRM-151 (Promedior Inc.) — a recombinant form of an endogenous human protein, Pentraxin-2 — acts as a monocyte/macrophage differentiation factor that may inhibit and potentially reverse fibrosis, according to a press release issued by the company.
In preclinical models, PRM-151 demonstrated anti-fibrotic activity in several types of fibrotic disease, including acute and chronic nephropathy, age-related macular degeneration, liver fibrosis and pulmonary fibrosis.
Beth Tréhu
The FDA based its decision on interim data from a phase 2 study. The findings, presented at the ASCO Annual Meeting in June, showed PRM-151 conferred benefit in several clinically relevant measures of myelofibrosis, including reduction in spleen size, decreased bone marrow fibrosis, symptom responses, and improvements in hemoglobin and platelets. The agent also demonstrated an acceptable safety profile with no treatment-related myelosuppression.
“We are extremely pleased to have received fast track designation for PRM-151, as we believe that PRM-151 offers the potential to better meet the needs of patients with myelofibrosis,” Beth Tréhu, MD, FACP, chief medical officer of Promedior, said in the press release. “This designation validates our perspective that there is a clear and compelling need for a novel mechanism for the treatment of myelofibrosis that specifically targets the underlying fibrotic processes of the disease. We will continue to work expeditiously to advance this program through the clinic and look forward to presenting the full data set from the first stage of our phase 2 study later this year.”
Perspective
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The accompanying article provides insights into this and other similar reports. That a macrophage-differentiating protein, Pentraxin-2 (also known as serum amyloid P) clears fibrosis in marrow — and evidently in pulmonary fibrotic syndromes, as well — suggests that transplanted macrophages may be responsible for the “McGlave phenomenon,” especially if they are appropriately stimulated by endogenous pentraxins.
Moreover, one might postulate that idiopathic myelofibrosis — at least in some cases — results from incompetent, mutated macrophages or from inefficient pentraxin-induced differentiation of normal macrophages. This suggestion can be examined and hopefully will be in the future.
Perspective
Back to TopEarly data from a phase 2 trial with PRM-151 in myelofibrosis — either with or without the JAK inhibitor ruxolitinib (Jakafi, Incyte) — revealed tolerability and safety, as well as broad activity, including regression of marrow fibrosis, improvement in cytopenias, reduction in spleen size and improvement in symptom scores (Verstovsek S. J Clin Oncol. 2014;32:5s.). Results are early and longer follow-up data are needed to answer important questions regarding the depth, duration and consequence of an anti-fibrotic effect in treated patients, including the potential to more definitively improve altered hematopoiesis and blood counts, which is somewhat lacking with the use of JAK inhibitor therapy, as well as complementing the symptom improvement, reduction in organomegaly and apparent survival improvements noted with JAK inhibitor therapy. Of interest, as well, would be potential correlation with reduction in clonal burden in the case of JAK2 (V617F) and other observed molecular drivers in myeloproliferative neoplasms.
Given the broad effects myeloproliferative diseases have on patients, we continue our quest for more comprehensive and more definitive therapy or combinations of therapy. PRM-151 may prove worthy in this venture and bears close watch.