Disappointing Results for “Prochymal” trials
In a recent article I described a hopeful new technology called “Prochymal” that I hoped would much improve control of graft-versus-host disease – the single most important hurdle standing in the way of safer stem cell transplants. I reviewed very encouraging results reported from Phase – II trials and I hoped the company’s pivotal Phase – III trials would confirm the earlier results and thereby earn rapid FDA approval.
I am sorry to tell you that the just announced results sound a whole lot less encouraging than I hoped. Below is a excerpt from the company’s statement.
Osiris Therapeutics, Inc.today announced preliminary results for two phase III trials evaluating Prochymal for the treatment of acute graft versus host disease (GvHD). GvHD, the most common complication of bone marrow transplantation, is a life-threatening disease for which there is currently no approved treatment. Prochymal showed significant improvements in response rates in difficult-to-treat liver and gastrointestinal GvHD, however neither trial reached its primary endpoint.
Key findings from the GvHD trials include:
- There was no statistical difference between Prochymal and placebo on the primary endpoints for either the steroid-refractory (35% vs. 30%, n=260) or the first-line (45% vs. 46%, n=192) GvHD trials.
- The primary endpoint for the steroid-refractory GvHD trial (durable complete response) for the per-protocol population approached statistical significance(40% vs. 28%, p=0.087, n=179).
- In patients with steroid-refractory liver GvHD, treatment with Prochymal significantly improved response (76% vs. 47%, p=0.026, n=61) and durable complete response (29% vs. 5%, p=0.046).
- Prochymal significantly improved response rates in patients with steroid-refractory gastrointestinal GvHD (88% vs. 64%, p=0.018, n=71).
- In pediatric patients, Prochymal showed a strong trend of improvement in response rates (86% vs. 57%, p=0.094, n=28).
One more time, I (we) have to face the reality that it is not a done deal until the last bit of information is in, until well designed and well conducted late stage clinical trials prove new drugs are really as good as they seem to be at first blush. The FDA is rightly unimpressed by trials that do not meet their primary endpoints. Neither am I. Of course, these results will be parsed every which way by experts and company spokespersons. But it seems clear Prochymal flunked a couple of very important tests.
We have been here before. Remember Genitope, their custom made “MyVax” vaccine was going to cure CLL with little to no toxicity? The company went out of business after it failed to show benefit in a pivotal trial. How about Genta’s “Genasense” (oblimersen)? It too failed to meet it pre-defined primary endpoints. So many drugs fall by the wayside when they face late stage trials. The list is depressingly long. Even my favorite Ofatumumab is teetering on the edge, FDA approval has been delayed longer than I hoped.
I try hard not to get too enthusiastic about Phase -II trial results. I have been burned too many times, I have come by my cynicism the hard way. But some times it is hard to resist the possibility of breakthrough good news just around the corner. Hope springs eternal, especially when there is precious little else to keep us going. I was really rooting for Prochymal’s successful completion of their Phase – III trials. So many patients with aggressive CLL need transplants. But until we learn to control GVHD more effectively, transplants will continue to be the toughest therapy decisions patients and their families have to face.
Well guys, I think we can put Prochymal on the back burner for now. Sorry. I wish I had waited a little longer, waited for the Phase – III results before publishing my glowing review just a few weeks ago. The least I can do is bring this disappointing sequel to your attention as well, hot off the presses.