Neurologists are backing the on an investigational drug for amyotrophic lateral sclerosis (ALS).
Genervon has previously released top-line data from its 12-week phase II trial of GM604 in 12 patients and has supposedly applied for accelerated approval status in ALS with the FDA, although neither the company nor the FDA will confirm that. But neurologists remain skeptical about the full data, which have not been released, especially as a large social media campaign, including a , has increased patient demand for access to the treatment.
"I understand their desperation, but we have to make sure we do no harm," , of the Houston Methodist Neurological Institute, told 鶹ý.
Appel applauded the for Genervon to release all of the data on GM604 to the public. If the company applied for accelerated approval, the FDA would have all of that data, but it is not legally allowed to make it public. Nor is the FDA allowed to confirm receipt of the company's application, a spokesperson for the agency told 鶹ý.
"The FDA's response is totally reasonable," Appel said. "It is totally unacceptable to be telling patients that there's a drug that works, and that they're being denied, when there are no such data."
, president and CEO of the ALS Therapy Development Institute, that he's not sure why the ALS community has rallied so strongly around GM604.
"Why not NP001? It is a drug that went through a much larger clinical trial and showed efficacy!" he wrote. "Why not tirasemtiv? A compound that went through several much larger trials in ALS and also showed some signs of efficacy. The data are certainly as good as those from GM604. Why not retigabine, memantine, rasagiline, TUDCA, NurOwn, or ozanezumab? You get the picture."
Several experts also cited the case of lithium for ALS, which looked promising in early data from a small Italian trial but ended up being a bust.
"Academia quickly conducted two larger trials that unfortunately showed conclusively that lithium was not effective in ALS," , medical director of the Penn ALS Association Center at Pennsylvania Hospital, said in an email to 鶹ý. "Had these trials not been conducted, and lithium had been approved for use in patients with ALS on the basis of small data without the proper placebo-controlled trials, then current and future generations of ALS patients would be on lithium, which was not only shown to be ineffective, but potentially harmful."
In Search of Accelerated Approval
Genervon says it was granted fast-track status for the drug in ALS in June 2013, followed by an orphan status designation in March 2014.
In October 2014, it released top-line results from its 12-week phase II trial in 12 patients, conducted at Columbia University in New York City and Massachusetts General Hospital in Boston. The company also released a case report from a single patient in January. It claims to have submitted all of these data "including statistical reports, raw data, and supporting documents" to the FDA in hopes of garnering accelerated approval of the drug. Those data have never been published.
The drug -- a peptide highly expressed in week 9 of human gestation, according to Genervon -- plays a role in nervous system development and is also being studied in Parkinson's and ischemic stroke.
Genervon says it met with the FDA in February to discuss next steps for its ALS indication, arguing for accelerated approval partly on grounds that "tens of thousands of ALS patients ... will almost certainly die before a phase III trial could be completed."
Accelerated approval would enable the drug to be distributed widely, to any ALS patient that wanted it, instead of the typical next step, which would be a phase III randomized, controlled trial to get a better picture of the drug's actual efficacy.
Neurologists contacted by 鶹ý prefer to see those phase III trials first.
"A larger and longer study is needed to determine both safety and efficacy for those with the disease," , of the University of Kansas Hospital in Kansas City, said in an email. "Giving a medication broadly without appropriate clinical trials exposes those with ALS to possible side effects that may reduce their quality of life, risks making them worse, and pulls money, personnel, and effort away from finding the cure."
But patients have not made the comparison between GM604 and the outcomes seen with lithium and other drugs. They held a in March calling for accelerated approval. More than 460,000 have signed on to the in support of bringing the drug to market. They've posted videos and started Twitter hashtags in support.
Genervon, based in Pasadena, Calif., has issued a on its website, many of which rely on strange rhetoric. In a response to Perrin's blog, the company writes his "intentional deception to the public has some pretty graphs" despite its "wrong assumptions," and that his "deception" is "evil."
A handful of releases are dedicated to putting the science into "layman terms," often going into detail about many of the results but never fully releasing the data.
Genervon owners Dorothy and Winston Ko -- she is a chemist, he is an architect -- said they were inspired to create the compound by this passage in the bible: "the lame will leap like a deer and the mute tongue shout for joy."
"This reported novel medication, by a biotech company, founded by two individuals that were inspired by a biblical prophecy, appears to be too good to be true," , chair of neurology at North Shore University Hospital on Long Island, N.Y., said in an email to 鶹ý. "I am fearful that the data may be inaccurate and produce false hope in the ALS community."