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naturally-occurring protein in humans called pentraxin-2 that works as a switch to halt and possibly reverse the formation of scar tissue. “[Pentraxin-2 works] really early in the process to kind of reset that whole environment.,” Bruhn says. The result, she says, is that cells that would otherwise develop into a form that causes damage instead wind up helping the bone marrow heal.
That’s all well and good, but where’s the proof? Promedior designed an adaptive, two-part Phase 2 trial: meaning Promedior first ran a small trial asking some big questions—like, is there a signal here that the drug is impacting fibrosis, how well does it work as a single agent and in combination with ruxolitinib, and should the drug be administered weekly or monthly? And, ultimately, do the answers warrant moving on to a bigger Phase 2?
Promedior is reporting the initial results of the first stage of that trial today. The company enrolled a total of 27 patients with either grade 2 or 3 fibrosis—a measure of their scarring—at the beginning of the study. They were broken into four groups and given either weekly or monthly doses of PRM-151 on its own, or in combination with ruxolitinib, over the course of 24 weeks.
Promedior took bone marrow biopsies at the beginning, middle and end of the trial. 18 patients have finished the study so far. Bruhn says three of the rest are still being tested, three withdrew, and three died, but that these were all older patients who had failed multiple JAK inhibitors, and that those withdrawals/deaths were largely no attributed to the drug.[Paragraph edited for clarity.]
“These folks are all very, very sick,” she says.
Promedior then measured the impact on bone marrow health, according to a scoring system that takes various side effects like spleen size and anemia into account (officially called the Myoproliferative Neoplasm Symptom Assessment Form). Seven out of the 18 patients had a 50 percent reduction in that score, and 5 of them saw their fibrosis reduced by at least one grade. A “number” of the patients on PRM-151 saw their levels of platelets and hemoglobin improve, though Bruhn wouldn’t specify how many. She says most of the side effects patients experienced were mild, and most were thought to be unrelated to PRM-151. [Paragraph edited for clarity.]
Still, this is a small sample size of patients, Promedior hasn’t even picked a dose for the next study yet, and the composite score isn’t an endpoint that would be used in a pivotal study. Further, though Promedior saw some patients with improvements to their fibrosis, others had signals of bone marrow health without anti-fibrotic evidence—so the company has plenty of things to figure out before it even starts the longer portion of its Phase 2 trial, let alone becomes a mover in the myelofibrosis field. But as Bruhn says, it’s a start.
“We’re excited,” she says. “This was a signal-finding, and we saw a signal in all four groups.”
Promedior was formed in 2006 and originally based in Malvern, PA. Bruhn, who spent most of her career at Transkaryotic Therapies (acquired by Shire in 2005) and had a hand in developing biologics for rare diseases like Fabre disease (aglsidase alfa, sold as Replagal) and Gaucher (velaglucerase alfa, sold as Vipriv), took over as CEO in May 2012. The company has raised a total of $76 million in venture dollars from the likes of Polaris Partners, Shire, and Morgenthaler.