- GM604 (also called GM6), in development by Genervon, has been associated with some functional and biochemical benefits in one 12-person trial and one single-person trial in people with ALS.
- The drug is believed to act as a "master regulator" of genes that are active in the nervous system.
- There is a community movement to make GM604 available to ALS patients as soon as possible, but the FDA is unlikely to approve the drug until larger, longer studies are conducted.
Biopharmaceutical company Genervon has announced what it considers encouraging results from a "compassionate use" trial of its experimental drug GM604 in a single patient with advanced amyotrophic lateral sclerosis (ALS).
In a Jan. 8, 2015, press release, Genervon said the patient, a 46-year-old man who had shown ALS symptoms for 10 years, showed small improvements in speech and swallowing during the 12-week study. In addition, the levels of some proteins used as biological indicators of disease progression moved toward the normal range in the patient's spinal fluid. No adverse side effects of GM604 were noted.
The data on the single patient follow encouraging results from a 12-person, phase 2a trial of GM604 in ALS, for which Genervon announced results in Oct. 19, 2014. Participants in this trial were randomly assigned to receive GM604 or a placebo and were observed and assessed for 12 weeks. To be in this trial, patients had to have experienced ALS symptom onset within the previous two years, so they were at an earlier stage of their disease than the compassionate use patient.
In the phase 2a trial, according to the Oct. 19, 2014, press release from Genervon, GM604 was associated with significant reduction in functional decline, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). In addition, the company also said that five patients showed a slowing of the decline in forced vital capacity, a measurement of respiratory function. Multiple proteins indicative of disease progression, measured in blood or spinal fluid, showed either a statistically significant or "strong trend" (less than statistically significant) change toward normal with GM604 treatment. The drug appeared to be safe and tolerable.
'Master regulator' GM604 has fast track and orphan drug designations
GM604, also known as GM6, is believed to be a "master regulator" of signaling in the nervous system, regulating levels of activity of multiple genes in such a way that protein production from these genes stays in or moves into a normal range.
GM604 has received fast track and orphan drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of ALS. These are mechanisms that the FDA has in place for speeding up the review process for new drugs (fast track designation) and encouraging development of drugs to treat rare diseases (orphan drug designation).
Evidence to date unlikely to lead to FDA approval
"It's important to note that the Jan. 8, 2015 report on GM604's possible benefits are from a study of a single patient," said Grace Pavlath, MDA's scientific program director. Pavlath, acknowledging that there is a community movement to hasten GM604's approval, noted that the FDA is unlikely to approve GM604 for use in ALS based on a single patient's results or even the 12-person, phase 2a results. "Both trials were very small and short in duration," Pavlath said. "However, any hint of efficacy in ALS is worth pursuing, and we hope that Genervon will continue to test this drug in larger and longer clinical studies."