FDA Calls for Data on ALS Drug

In the midst of a debate about an experimental drug’s early approval, the US Food and Drug Administration requests that full trial results be released.

Following the completion of a 12-person, Phase 2 trial testing its drug candidate, GM604, for the treatment of amyotrophic lateral sclerosis (ALS), California-based biotech Genervon announced“very robust” and “dramatic” results and applied to the US Food and Drug Administration (FDA) for accelerated approval. If granted, the status would allow the company to skip Phase 3 trials for the drug, following up with additional studies after it hit the market. ALS patients have petitioned for the approval of GM604; researchers have demanded caution.

The FDA has remained tight-lipped on the issue, as by law it cannot discuss ongoing drug evaluations. Instead, the agency last week (April 16) called on the company to publicly release the all data from the Phase 2 study, rather than a mere summary of the results, upon which advocates and skeptics have so far based their arguments.

“We call upon Genervon to release all the data from their recently completed trial in order to allow a more informed discussion of the trial findings among ALS stakeholders,” the FDA wrote. “Such a release should include the pre-specified clinical outcome measures as assessed by change from baseline observations that were taken just prior to randomization to drug or placebo. Such data provide the strongest basis to assess for drug-related changes in efficacy and safety parameters.”

The day before the agency released its statement, GM604 skeptic Steve Perrin, president and chief scientific officer of the ALS Therapy Development Institute, penned a blog post in which he argued that the supposedly breakthrough results achieved in the Genervon trial were not as exciting as they may seem. The company had stated that forced vital capacity (FVC), a measure of lung capacity, declined just 5.6 percent among patients in the treatment group, while it declined 22 percent among patients taking a placebo. But Perrin’s analysis found that a historical sample of 777 ALS patients, pulled from a public database, had a decrease in FVC of just 4.33 percent for a comparable period. “Should we really believe that the placebo group from the Genervon trial, with its 22% decline over the same duration, can fairly represent the overall ALS patient population?” Perrin wrote.

Of course, without access to the actual Phase 2 data, there is no way to draw a direct comparison. And Genervon maintains that critical data for evaluating the GM604’s true efficacy can come in an aftermarket study. “Through APP [accelerated approval program], the FDA can get the large population data they could never get from Phase 3 trials while at the same time today’s 30,000 ALS patients in the US will have access to treatment options,” the company wrote in a statementresponding to Perrin’s blog post. “It takes a lot more courage for Genervon to allow GM604 to be exposed to a full spectrum of heterogeneous ALS patients through AAP with Phase 4 surveillance requirements than pursuing the much safer route of a very narrowly defined, controllable, small number of ALS patients in a Phase 3 trial.”