Osiris began its mesenchymal stem cell program in 1992 and won approval to begin Phase III trials in 2006. “We’re the senior citizen of stem cell companies,” Doug Jacobstein, M.D., senior director medical affairs, joked. Since then, Osiris has expanded its stem cell program to include anti-inflammatory applications.
“We have fast-track status for two indications: acute graft versus host disease (GvHD) and Crohn disease,” Dr. Jacobstein said. GvHD affects about half of all transplant patients, and there is no approved therapy. Standard treatment starts with high-dose steroids, which more than half of patients fail.
Protocol 280, a trial for steroid refractory GvHD, combined the physician’s choice of second-line therapy with either Prochymal® or a placebo. “Prochymal achieved an overall response in 82 percent of patients with gastrointestinal GvHD and in 76 percent of patients with GvHD of the liver,” Dr. Jacobstein reported.
Another trial, Protocol 275, involved 59 pediatric patients, of which 92% had visceral organ involvement, 88% had the most severe forms of GvHD (Grades C/D), and 63% had multiple organ GvHD. “At day 28, 63 percent had responded to Prochymal, with a median improvement of two grades.” Of patients who responded at 28 days after treatment, 78% were alive at day 100.
“Fast Track status didn’t affect the study design. The benefit is that it allows more frequent meetings and conversations with the FDA and allows a rolling review so the BLA—for example—may be filed in sections.” An NDA priority review under Fast Track takes about 6 months, versus about 10 months for nonpriority review.
Juventas Therapeutics gained FDA approval to initiate Phase II testing in critical limb ischemia using its lead compound, JVS-100, in January. Currently, there is no FDA-approved therapy, according to Rahul Aras, Ph.D., CEO.
JVS-100 encodes stromal-cell derived factor 1 (SDF-1). As Dr. Aras remarked, “SDF-1a is a very interesting molecule.” SDF-1 repairs the heart after myocardial infarction by activating the natural repair pathways, promoting the growth of new blood vessels, and preventing on-going cell death. Early studies indicate it may repair the heart when administered even a few months after a cardiac event.
“Results are promising,” he said. Specifically, “in the six minute walk, patients improved by 36 meters in four months and gained 22 points in quality-of-life measurements, and about half improved one full cardiac class.”
JVS-100 has the potential to be a platform drug, with applications after ischemia and traumatic injury to the brain, kidney, liver, lungs, and dermis. “We also have topical approaches to accelerate wound healing.”