An FDA advisory committee Thursday voted 9-1 to recommend that the agency approve a stem cell therapy developed by MesoBlast as a treatment for acute graft-versus-host disease (aGVHD) in children. The panel weighed the need for a new way to address the potentially fatal condition against shortcomings of the clinical trial the Australian biotech conducted to evaluate the investigational cell therapy.
Shares in (NASDAQ: MESO), which fell more than 30 percent earlier in the week after the FDA released briefing documents ahead of the committee’s meeting, closed up 51 percent Friday at $17.88 apiece compared to $11.81 at market close Wednesday. (Trading was halted on Thursday.)
The MesoBlast cell therapy, remestemcel-L (Ryoncil), is made from mesenchymal cells taken from healthy donors. The properties of these cells, which don’t prompt an immune reaction, allow them to be used as an “off-the-shelf” treatment without accompanying immunosuppressants that put patients at greater risk for infection, among other side effects.
Some patients with blood cancer are treated with a stem cell transplant, in which cells from a healthy donor are infused into their bloodstream with the intent that those cells will travel to the bone marrow and form new healthy blood cells. Frequently, however, when donors are unrelated, their cells identify the recipient’s as foreign, prompting them to attack organs and tissues. Treatment with systemic corticosteroids can help control the severity of the condition. But in up to 90 percent of aGVHD patients who don’t respond to steroid treatment, the condition can prove fatal.
MesoBlast’s submission was based on a clinical trial that enrolled 55 children age 2 months to 17 years who had received a transplant of bone marrow, peripheral blood stem cells, or cord blood, were diagnosed with aGVDH and weren’t responding to steroid therapy. The study tracked their responses to remestemcel on day 28. Overall, 70 percent of the patients responded, including 76 percent of the 25 patients whose condition was graded as most severe. On day 100, 74 percent of patients remained alive; on day 180, 69 percent.
However, the trial was neither randomized nor controlled, raising concerns of confounding factors and potential bias. MesoBlast said investigators weren’t willing to enroll children in such a trial. But the company said randomization and controlled design would be incorporated into a planned post-marketing study in adults.
In previous clinical trials in wider patient populations, the treatment missed the primary goal. Analyses of results from those earlier trials prompted MesoBlast’s decision to focus the drug’s further development to steroid-refractory pediatric patients. In its presentation to the advisory panel the company said the remestemcel manufacturing process has been improved since those trials in ways that have made the treatment more potent.
The panel voted on whether MesoBlast provided enough clinical data to show that its therapy was effective in treating aGVHD in this narrower group. Panelist Christian Hinrichs, a clinical researcher at the National Cancer Institute and physician by training, was the sole “no” vote. Nine panelists felt the available data did indicate efficacy. (The committee recorded the tally as 8-2, but a MesoBlast representative said one “no” vote was made in error.)
“I do think that the two prior randomized trials convincingly show that the [earlier version of remestemcel], at least in the population that was being studied, which is similar but not the same, clearly did not have meaningful activity,” Hinrichs said. “So, you know, do we think that these tweaks to the manufacturing have suddenly made it highly effective, and the change in patient population has suddenly made it highly effective?”
Jorge Garcia, division chief of solid tumor oncology at University Hospitals Seidman Cancer Center in Cleveland, however, said while it isn’t clear how the treatment compares to other drugs used to treat patients with the condition, the data indicate it is safe and has shown “some efficacy.”
In May 2019 an Incyte (NASDAQ: INCY) treatment, ruxolitinib (Jakafi), became the first FDA-approved treatment for patients with aGVHD who didn’t responded to steroid therapy. Ruxolitinib was OK’d for patients starting at age 12. But no treatment is approved for those younger.
Although the FDA considers advisory panel recommendations during drug reviews, committee recommendations are not binding, and the agency doesn’t always follow them. Its decision on remestemcel is anticipated by September’s end.
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