For people with amyotrophic lateral sclerosis, which attacks the body’s motor neurons and renders a person unable to move, swallow or breathe, the search for an effective treatment has been a crushing disappointment. The only drug available for the disease, approved two decades ago, typically extends life just a few months.
Then in the fall, a small California biotech company named Genervon began extolling the benefits of GM604, its new ALS drug. In an early-stage trial with 12 patients, the results were “statistically significant,” “very robust” and “dramatic,” the company said in news releases.
Such enthusiastic pronouncements are unusual for such a small trial. In February, Genervon took an even bolder step: It applied to the Food and Drug Administration for “accelerated approval,” which allows promising treatments for serious or life-threatening diseases to bypass costly, large-scale efficacy trials and go directly to market.
ALS patients responded by pleading with the FDA, in emotional videos and e-mails, to grant broad access to the experimental drug. Online forums lit up, and a Change.org petition calling for rapid approval attracted more than a half-million signatures.
“Why would anyone oppose it?” asked ALS patient David Huntley in a letter read aloud in the past week at a rally on Capitol Hill. Huntley, a former triathlete, can no longer speak or travel, so his wife, Linda Clark, flew from San Diego to speak for him.
“This disease is evil,” Huntley wrote. “It doesn’t just kill you; it takes away everything that you care about, one at a time, then it kills you. Tell me how some as-yet-to-be-detected side effect is going to degrade my quality of life?”
Now, the FDA must weigh its mandate to ensure new drugs are safe and effective against the demands of patients such as Huntley, who say they should be allowed to try experimental treatments and are willing to accept the risks.
This isn’t the first time desperate patients have launched a social media campaign to try to compel the FDA to act. But in this case, the effort also has laid bare stark divisions within the ALS community, where some advocates, patients and researchers — including one who helped lead the clinical trial — have criticized the company’s tactics.
Few pharmaceutical companies, they say, would push for accelerated approval based on a 12-week trial involving just 12 people. And they warn that short-cutting the traditional clinical-trial process could make it more difficult to tell whether GM604 really works.
“All this petitioning and press releases over such little data is premature,” said David Gortler, a pharmacology expert and former FDA senior medical officer. He said the company hasn’t made the case that its drug deserves accelerated approval, adding, “I think Genervon is preying on the lack of information that the average person has about the drug-development process. . . . You can’t rush the scientific process. Good science takes time.”
Steve Perrin, president and chief scientific officer of the ALS Therapy Development Institute, a nonprofit dedicated to developing effective treatments, is even more blunt. “The bottom line with the Genervon drug is there is absolutely no data,” he said. “There is no mathematical way or statistical way that they could measure a drug effect.”
A Columbia University researcher who helped run the clinical trial for Genervon says the results so far fall short of the company’s assertions, and more research is needed. Even the ALS Association, which last year raised more than $115 million through its “Ice Bucket Challenge,” says making the drug broadly available at this point would expose patients to possible side effects and “pulls money, personnel and effort away from finding the cure that all of us are working together to find.”
Dorothy and Winston Ko, the owners of Pasadena-based Genervon, insist their results are strong enough to warrant speedy approval. “The data is highly, highly robust,” Winston Ko said in an interview. “Why would I push it if I’m not confident that our innovative, novel drug discovery is not effective?”
Thousands of ALS patients and their loved ones also remain hopeful about the drug. Scores of people from around the country recently attended the Capitol Hill rally, waving signs that read, “Give us the right to try GM604” and “Time is NOT on our side.”
Eric Valor, 46, an ALS patient who lives in California, says the apparent safety of the drug, coupled with its potential, makes it an ideal candidate for pressing the FDA to change the way it approves drugs for the terminally ill, a process he thinks is too slow and risk-averse.
“I understand the need for data and deplore false hope and its effect on PALS [people with ALS],” he wrote in an e-mail. “However, the current FDA review paradigm has to change. . . . It’s a balance between hope and hard science.”
At any one time, about 30,000 people in the United States have ALS, and some 5,600 are diagnosed each year, according to the ALS Association. Most live an average of two to five years after being diagnosed.
The FDA has granted accelerated approval for multiple drugs in the past, including three in 2014, according to the agency. The most recent was a drug for metastatic melanoma that showed remarkable results in early trials involving 370 people. The agency declined to comment for this story, saying it is prohibited from discussing pending drug applications.
If the FDA grants accelerated approval for GM604, thousands of patients potentially could get access to a treatment that has been tested in a small number of humans, primarily for safety.
The agency traditionally has been reluctant to grant such approvals without strong indications a drug will prove effective. Advocates for GM604 note the FDA could approve the drug and require follow-up studies on its long-term risks and benefits. But some experts say it can be hard to get patients to enroll in such “confirmatory” trials and to compel companies to complete them after a drug is already on the market.
If the FDA denies accelerated approval, the drug would probably face years of additional clinical trials that might well produce more reliable results. Any subsequent approval would probably come too late for today’s ALS patients.
Winston and Dorothy Ko founded Genervon Biopharmaceuticals in 2002 after being inspired by the biblical prophecy that “the lame will leap like a deer, and the mute tongue shout for joy,” according to their Web site. Winston is the chief executive officer and an architect; Dorothy is chief operating officer and has a master’s degree in chemistry.
The Kos also own an anti-aging research company called Dermacare Neuroscience Institute in Beverly Hills, and they founded the Agape Bible Missions Church in Monterey Park. The couple, who filed for Chapter 7 bankruptcy in 2003, also previously owned a company named KM Biotech, records show.
Winston Ko says he has been in business a long time and is used to ups and downs. “If you work in the kitchen, you have to be able to stand the heat,” he said.
GM604 is a peptide, or chain of amino acids, which is aimed at promoting the survival, growth and maintenance of selected cell populations — in the case of ALS, motor neurons, which reach from the brain to the spinal cord to the muscles responsible for movement, including swallowing and breathing. Genervon is developing similar treatments for stroke and Parkinson’s.
The recent ALS trial involving GM604, which took place at Columbia University Medical Center and Massachusetts General Hospital, occurred over two weeks, with eight ALS patients receiving a total of six doses of GM604. Four patients received a placebo. The patients were then followed and tested, chiefly for tolerance of the drug, over the next 10 weeks.
“The differences between the treated groups and the placebo groups were statistically significant despite the fact that the trials were small and thus not powered to produce such dramatic effects,” the company wrote in a February news release.
Genervon also cited Paul Lupinacci, a Villanova University professor of mathematics and statistics who analyzed the trial data for the company. He said in an interview that even a small trial can produce statistically significant results, and the GM604 trial was an example of that.
But Perrin, of the ALS Therapy Development Institute, says those differences in such a small trial are meaningless because ALS patients decline at different rates.
“Honestly, if there were 30 people in your office and all diagnosed with ALS in early stages, you couldn’t tell by looking at them who is going to lose their battle in six months because they’re a fast progresser and who is going to last three or seven years,” he said. “So the only way to test the drug’s effect is to test it in hundreds of patients.”
Hiroshi Mitsumoto, medical director of the Eleanor and Lou Gehrig MDA/ALS Research Center at the Neurological Institute of New York, oversaw the GM604 clinical trial at Columbia University Medical Center. He grew disturbed by the company’s interpretation of the data in its news releases.
“When [Genervon] started putting out things [about significant results], we said, ‘That’s not true,’ ” Mitsumoto said, referring to himself and the other principal investigator, Merit Cudkowicz, director of Massachusetts General Hospital’s ALS clinic. “I think a large study is needed, and they [the Kos] don’t understand.”
Cudkowicz declined interview requests, but a spokesperson at Mass General said the researcher “has been participating in the GM604 trial since it began and intends on seeing it through until everything has been completed. This is technically when the results are published.”
Winston Ko said given the drug’s apparent safety, it would be unethical not to allow broad access if there’s any evidence it might help. The company previously has said it received a “fast track” designation from the FDA, which provides for expedited review of a promising drug but does not allow it to skip clinical trials.
“If I have to do a [larger trial], they will all die; most of them will die,” he said of current ALS patients. “Even if it doesn’t work . . . they have something.”
Last year, Valor, the California ALS patient, became the only person to receive GM604 through the FDA’s “compassionate use” exemption, which allows individuals with serious illnesses to receive an experimental drug. He said his limited treatment gave him a “small but detectable” improvement in speech clarity and increased the amount of water he could hold in his mouth — a big deal, he said, because it allows him the simple pleasure of enjoying a beer at the end of the day.
“My improvements are slight because I am a very late-stage patient,” he said, “but nonetheless surprising that any improvements in condition happened at all.”
Nick Grillo, a 54-year-old ALS patient from San Francisco and one of the sponsors of the Change.org petition, said those not battling the disease can’t grasp what it feels like to have no real treatment options.
“Truth is, there isn’t anything else in the pipeline,” he wrote in an e-mail. “Personally, I’d rather die a guinea pig and contribute to research than to sit at home and waste away.”
The history of ALS is littered with failed clinical trials. A recent disappointment came in early 2013, when Biogen halted the development of a much-anticipated ALS drug after studies showed it didn’t improve patients’ quality of life or survival.
Still, some people who have dedicated their lives to finding a cure for ALS say accelerated approval of the Genervon drug isn’t the way to achieve that goal. Bernard Muller, an ALS patient from the Netherlands who co-founded a company to map the DNA of ALS patients, said he appreciates Genervon’s efforts. But, in an e-mail, he said Genervon’s claims of efficacy are thus far “poorly documented and not backed by sufficient evidence-based scientific publications.”
The ALS Association, which has received withering criticism from patients for not being more supportive of GM604, says due diligence is necessary. “We share the sense of urgency that exists for people living with ALS and their families,” said Barbara Newhouse, the group’s president, echoing a letter the group sent earlier this year to ALS patients that was signed by 13 scientists and research groups.“Bypassing clinical trials, however, could severely compromise drug development and safety.”
The debate over GM604 comes as a growing number of states have adopted “right to try” laws aimed at giving terminally ill patients access to experimental drugs that have passed initial safety tests but haven’t been approved by the FDA. At least nine states have passed such laws. Dozens more are considering them.
ALS patients and family members pushing for GM604, including many at the recent rally on Capitol Hill, say they merely want the FDA to use its existing legal authority to give accelerated approval to promising drugs for dire conditions.
“We’re not trying to rewrite laws today,” ALS patient Stephen Finger, 37, of South Carolina, told those assembled on the cold, gray afternoon. “All we need is the FDA to follow the directives issued to them by Congress.”
Mike Clarke, a 46-year-old patient from Atlanta, came to the rally hoping to add his voice to the chorus pushing for faster access to new drugs. “If it doesn’t happen while I’m here,” he said, “maybe it will happen when I’m gone and help someone else.”
At the center of the gathering stood an ice sculpture in the form of a two-handled bucket, a reference to the Ice Bucket Challenge that went viral on social media last summer. Hours later, all that was left of the sculpture was a jagged shell and a wet stain blooming slowly across the sidewalk. The melting of the ice, rally organizers said, symbolized the lives lost to ALS.
Advocates are already planning another rally in Washington for May 11.
Alice Crites contributed to this report.