Almost three months after Osiris Therapeutics Inc.'s Prochymal failed in Phase III trials for Crohn's disease, news of unfavorable interim Phase II data in chronic obstructive pulmonary disease dented the stock and left some investors on edge about the next indication, graft-vs.-host disease.
Columbia, Md.-based Osiris said Wednesday that the product, made of adult mesenchymal stem cells, proved safe but did not significantly improve lung function. At the end of the trading day, the company's stock (NASDAQ:OSIR) had fallen by $1.03, to close at $12.90.
Partnered with Genzyme Corp., of Cambridge, Mass., Prochymal was tested in 62 COPD patients, 58 percent of them male, ranging in age from 47 to 80 and suffering disease levels that ranged from moderate (23 patients) to severe (39). Patients had been afflicted for an average of 7.8 years, and those who also had asthma were excluded from the trial.
All participants took their four infusions with no evidence of related toxicity. Oxygen saturation levels showed no events either, and adverse event rates were comparable for patients receiving Prochymal and placebo.
Prochymal did, though, knock down c-reactive protein levels to a significant degree compared to placebo in patients who had elevated CRP (>4 mg/L) when they entered the study. The difference was clear at 10 days after the first infusion, and stayed low during treatment and follow-up.
CRP is often higher in such diseases as Crohn's, where Prochymal failed in late March. The trial was tainted by a higher-than-expected placebo response and the possibility of bias in patients' reporting, Osiris said, and the trial was starting over. (See BioWorld Today, March 30, 2009.)
In GvHD, too, elevated CRP is an important factor. September is expected to bring data from two pivotal Phase III trials in that indication. One study randomized 244 steroid-refractory patients, and the other randomized 190 patients with newly diagnosed GvHD.
Signed in late 2008, the deal between Genzyme and Osiris provided the latter with $130 million up front and as much as $1.25 billion in milestone payments. Also included in the deal is Chondrogen, a Phase I/II mesenchymal adult stem cell candidate for osteoarthritis of the knee. (See BioWorld Today, Nov. 5, 2008.)
Company officials were traveling and not available Wednesday, as analysts debated the meaning of the latest results. "Prochymal fails again," wrote Lazard Capital Markets' Joel Sendek in a same-day research report, adding that efficacy in the refractory GvHD indication would not be enough to drive profitability. Sendek had a "sell" rating on Osiris' shares.
At the opposite end of the spectrum was Charles C. Duncan, of JMP Securities, who rated Osiris "market outperform" and wrote that the good safety data lowered the risk for approvability. "Although not statistically significant nor an observation that we are basing our bullish view on, treatment with Prochymal did demonstrate positive trends in improving pulmonary function, including the six-minute walk test," in Duncan's view.
Landing in the middle was Edward A. Tenthoff, analyst with Piper Jaffray, who pointed to the CRP data and its meaning for GvHD. Tenthoff wrote that he was "optimistic we'll see positive results" from that trial in the fall, with potential fast-track approval in that indication in the first half of next year.