UPDATED: The FDA challenges Genervon to release data from controversial ALS study

Steve Perrin

Yesterday, FierceBiotech reported how an expert review of a tiny study for Genervon's ALS drug GM604 raised serious questions about the data that were provided by the company, which has aroused a furious campaign by ALS patients to gain an accelerated FDA approval. Today, in a rare break from the agency's standard "no comment" approach to experimental drugs, the agency called on the biotech to come clean and publicly release the actual results.

"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, noting the ALS community's interest, says in its statement. "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."

That's a remarkable position for an agency that abides by strict rules when it comes to the way it handles data, leaving it to biotechs to handle the talking points. A spokesperson for the agency noted that they had seen the Perrin piece, but said that today's statement had been in the works "to address the ongoing questions we've received about that drug from many people, including patients, families, media, etc."

Genervon's tiny 12-person study, with four people assigned to a placebo arm, assessed the drug's performance on several biomarkers for the disease, which would not be sufficient to gain an accelerated approval. But it also assessed an impact on ALSFRS-R rates and forced vital capacity, or FVC, among the patients. Genervon has not publicly revealed the ALSFRS-R data, which should reflect a specific change from baseline in patient performance. It did discuss, with considerable fanfare, what the biotech claimed was a major improvement in the rate of decline for FVC compared to placebo as well as one remarkable case in which a compassionate use patient experienced a rebound from the disease.

Reviewing the FVC data, Steve Perrin, president and chief scientific officer of the ALS Therapy Development Institute and an early skeptic of this drug, says the data didn't hold up on a review of a public database including hundreds of ALS patient experiences that could be used as a comparison measure. In that comparison, Genervon's drug arm actually performed slightly worse than the database average. There was no big improvement for patients taking GM604, says Perrin, raising questions about the way in which the data were collected, the patients were screened and selected for this study, and its importance to the ALS community.

"Based on the modeling demonstrated here from a very large patient cohort it does not appear plausible that the cohort of patients enrolled in the Genervon trial would represent a 'normal' cohort of ALS patients," Perrin noted. "Therefore based on the model I continue to be very skeptical that there is any way that GM604 could have provided any therapeutic benefit in this small of a trial with this short of an exposure."

While patients often say that this drug represents their only hope, Perrin has been quick to point out that there are a number of ALS drugs in the clinic. And if the patient campaign were to succeed, patients taking the drug would be excluded from trials for a drug that might actually work.

FierceBiotech followed up by asking Genervon CEO Winston Ko a simple question: Has the company actually filed a new drug application--which would be necessary for any kind of approval, accelerated or otherwise, that it's been demanding--and how has the FDA responded? If an NDA was filed, then the agency would have had a chance to see if the application was acceptable for review, or not.

The company, which is based in Pasadena, CA, and has cited biblical prophecy as an inspiration for its work, did not answer this question in a reply to FierceBiotech Friday afternoon. In an e-mail, Genervon did say it was considering the FDA's request, then repeated its demand for an immediate approval in order to save the lives of tens of thousands of patients.

"Through (accelerated approval)," the company wrote, "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. 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. It is a more secure and conservative approach to go through the traditional phase 3 trial and then apply for a New Drug Application. We do not think that people really understand the risk Genervon is taking to try and save the lives of 30,000 US ALS patients alone." 

Then the company turned to attack Perrin. Here's a passage: 

"Did Perrin threatened (sic) all ALS patients who have or will be receiving GM604 treatment in your blog? When can his compound(s) be ready for trials? Have they passed all the preclinical tests? Perrin should declare with full disclosure of his conflict of interest. If GM604 is approved can his company survive or continue to get donations? Journalists has (sic) the responsibility to tell their readers. Perrin is challenging the integrity without proof of the two prominent PIs contracted by Genervon to screen, enroll and collect data according to the FDA approved protocol. Perrin is wrong by ignoring the facts (sic) that FDA approved protocol per our PI suggestion that we enrolled only very fast progress patients as disclosed in clinicaltrials.gov, only definite ALS patients and within 2 years of ALS onset...Perrin did not show any data or how he come up with his data. He made claims without basis."  

FierceBiotech also contacted the two investigators for this study, Hiroshi Mitsumoto at Columbia University Medical Center and Merit Cudkowicz at Mass General.

Mass General's media group responded, saying that "unfortunately (Cudkowicz) will be unable to comment until the results have been reported in a peer-reviewed publication." Mitsumoto has not returned numerous messages in recent days.

- here's the FDA's statement