ALS Drug Access Debated

Biotech company Genervon has requested accelerated approval for its experimental ALS drug after a small but promising Phase 2 trial. Patients advocate for its acceptance, while researchers urge caution.

By | April 7, 2015

FLICKR, SLGCKGCLast fall, California-based biotech Genervon announced results of a Phase 2 trial involving 12 amyotrophic lateral sclerosis (ALS) patients: its drug candidate, GM604, had produced “very robust” and “dramatic” results, according to company news releases. In February, the company applied to the US Food and Drug Administration (FDA) for accelerated approval, which would allow the drug to skip Phase 3 and head straight to market. Patients, who typically only live two to five years past diagnosis and have no effective treatment options, quickly began advocating for the FDA to grant the company’s request, but many researchers believe that a larger trial is necessary before the drug becomes widely available, The Washington Post reported last week (April 3).

“All this petitioning and press releases over such little data is premature,” David Gortler, a pharmacology expert and former FDA senior medical officer, told The Washington Post. “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.”

But time is not something that most ALS patients have at their disposal, and advocates for GM604’s accelerated approval argue that, if the drug is forced to continue down the traditional clinical trial path, the majority of today’s patients will have died before it reaches the market. Patients and advocates have thus petitioned for its rapid approval, collecting more than half a million signatures on Change.org and organizing a recent rally on Capitol Hill.

But Steve Perrin, president and chief scientific officer of the ALS Therapy Development Institute, argued that, due to the variability in rates of decline among ALS patients, the Phase 2 trial was too small to generate meaningful results. Only eight ALS patients were treated during the trial, while four patients received a placebo. “The bottom line with the Genervon drug is there is absolutely no data,” Perrin told The Washington Post. “There is no mathematical way or statistical way that they could measure a drug effect.”

In addition to the Phase 2 results, the company in January announced positive results with a single patient given the drug through an expanded-access program. That patient, Eric Valor, who is no stranger to trying experimental therapies (see “Do-It-Yourself Medicine,” The Scientist, March 2013), supports GM604’s accelerated approval, noting his mild improvements despite his advanced condition. “I experienced slightly clearer speech and I can almost guzzle beer again,” he told The Scientist in February.

The debate also highlights the slow and risk-averse nature of the regulatory process, even in the context of approving drugs for the terminally ill, said Valor. “[T]he current FDA review paradigm has to change,” he told The Washington Post last week. “[There must be] a balance between hope and hard science.”

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Avatar of: test tube

test tube

Posts: 1

April 7, 2015

My Sister, wonderful and brilliant, is dying of ALS.  She, along with many others with ALS, Would eagerly take this drug and have their data used as part of a scientific study. They are not risk-averse.  They know they are going to die slowly and terribly.  If the drug kills them, it kills them.  They deserve the chance to take the drug.     

Avatar of: NGrillo

NGrillo

Posts: 1

April 7, 2015

Why we believe Accelerated Approval is the better option for GM604.

While researchers are calling for more clinical trials for Genervon’s GM604, we recognize that the FDA’s Accelerated Approval Program (AAP) is a preferable and an appropriate alternative. Let's look at why that is true:

1) There is an urgent and unmet need to get a viable treatment to People with ALS (PALS). The only option at this time is Rilutek, which extends life expectancy by a few months with no improvement to quality of life. The average life expectancy for PALS is 2-5 years. So by the time another clinical trial for GM604 is completed, the majority of the current generation of PALS will be dead. AAP was designed to meet the needs of populations just like the ALS Community.

2) The common clinical trial design limits patient inclusion to those diagnosed within 2-3 years of trial commencement and those exhibiting an "average" disease progression. In ALS, the notion of an "average" patient is scientifically invalid and indeterminable. This gap in knowledge precludes determining the number of patients to recruit in order to create a valid sample population. This common trial design yields no data on efficacy in late or early stages of the disease.

3) For GM604, AAP is a superior choice over a Phase 3 trial because AAP has the ability to yield more data sooner, across a broader spectrum of patient profile, and at far lower cost. Post-approval studies could include focused single arm trials designed to ask specific questions regarding correlation of clinical outcomes and biomarker responses, and a patient registry to capture more limited but still meaningful data from a larger population of patients (but not necessarily all) receiving the drug as an approved medicine.

Why is the ALS Community so excited about GM604? It's safe, we like the data provided (see links below), and we believe in Genervon's innovative approach.

1) GM604 is a 6-amino acid endogenous peptide. It is very safe and tolerable as shown in Phase 1 (32 subjects), ALS Phase 2A (12 subjects), Parkinson’s Disease Phase 2A (6 subjects), Stroke (28 of 36 subjects, not yet un-blinded). Adverse events and serious adverse events were comparable to placebo, with no reported drug related clinically serious adverse events.

2) In the 1990s, Genervon realized that the many failures of clinical trials for central nervous system diseases can be attributed to the fact that the classic drug development paradigm - designing single-target drugs - simply cannot account for the multifactorial nature of these complex diseases. Instead, Genervon's drug development strategy was to find the endogenous regulator(s) that control the development and function of the nervous system by modulating the expression of multiple genes through different pathways, thus bringing homeostasis and health to the biological systems. Genervon has received both fast track and orphan drug designations for GM604 in the treatment of ALS.

3) Bottom line: a Phase 3 trial for GM604 would result in the same data, more slowly, at higher cost, while AAP with required patient data surveillance could be used to not only broaden experimental drug access to patients in need of medical options, but also to gather data on a spectrum of patients that is more representational of the whole population.

Whatever you do, don’t rely on anyone else’s opinion. Educate yourself about GM604 by reading the information in the links below and consider our position. Then, decide for yourself if ALS patients and researchers will both benefit from an FDA program that is already in place to meet urgent and unmet needs of the terminally ill.

http://www.genervon.com/genervon/medicines_trialdata.php

https://docs.google.com/viewer?a=v&pid=sites&srcid=ZGVmYXVsdGRvbWFpbnxhYXA0Z202fGd4OmRjMThlZmVmN2Y1NGI0OA

https://docs.google.com/viewer?a=v&pid=sites&srcid=ZGVmYXVsdGRvbWFpbnxhYXA0Z202fGd4OjE2ZDZmOGQ2MjYwMmFiNQ

https://www.youtube.com/watch?v=45vVnjKlFxM

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