An experimental drug treating amyotrophic lateral sclerosis (ALS) is demonstrating promising potential, both slowing the progression of this neurodegenerative disease and prolonging patient survival. Phase 2 human trials are complete and Amylyx Pharmaceuticals, the company developing the treatment, says it is working with regulatory bodies on the steps necessary to bring the drug to market ahead of a Phase 3 trial.
AMX0035 is an experimental co-formulation of two separate drugs: sodium phenylbutyrate and taurursodiol. The formulation is designed to slow, and possibly prevent, neurodegeneration associated with motor neuron dysfunction.
For the last few years AMX0035 has been tested in a Phase 2 human trial with a cohort of 137 subjects. The primary results of the trial were published in The New England Journal of Medicine in early September. Those results revealed that, after a 24-week treatment, the drug leading to a “clinically meaningful and statistically significant” benefit.
At the end of the initial 24-week, placebo controlled study, all participants were offered the opportunity to take part in an open-label follow-up to investigate the drug’s effect on long-term survival. The vast majority of the cohort agreed to take part.
Three years later and the new study reveals those subjects initially randomized to AMX0035 had a 44 percent lower risk of death, compared to those subjects originally in the placebo group. This equates to those original AMX0035 subjects living an average of six and half months longer than the placebo group.
“This is one of the first studies to show effect on both function and survival,” says senior author Merit Cudkowicz. “We are hopeful that this is just the beginning of many new treatments for ALS.”
The experimental drug proved relatively safe in the trial, with an equal number of adverse effects reported in both active and placebo groups.
Traditionally at this point a new drug would move into larger Phase 3 human trials, validating these results in a bigger and more diverse cohort. However, this next phase will take significant time and money to complete, meaning at best the drug would not be publicly available for several more years.
The ALS Association, a co-funder of the AMX0035 Phase 2 trial, recently launched a public petition calling for the US Food and Drug Administration (FDA) to make the drug urgently available to ALS patients now, foregoing the usual Phase 3 trial requirements.
“Given the large phase 2 sample size, clinically relevant slowing of disease progression, and significant evidence that the drug is safe, the Association and I AM ALS launched the petition asking that Amylyx and the FDA move with urgency make this drug available for all people living with ALS,” the association writes. “People with ALS cannot wait for a phase 3 trial to conclude given the promising results shows in phase 2.”
It is not unusual for some drugs to begin to be delivered to patients before Phase 3 trials are complete. The FDA’s Expanded Access and Compassionate Use protocols are expressly designed to accelerate access to promising life-saving medicines as soon as possible. But, it would be somewhat unusual for full approval of a drug to be made without any larger Phase 3 investigation even commencing.
In a statement accompanying this latest study outlining the results of the Phase 2 trial, Josh Cohen, co-CEO of Amylyx, suggests there are ongoing discussions with regulatory agencies looking at everything necessary to bring the drug to patients as soon as possible.
“These results provide evidence to support the rapid advancement of AMX0035,” says Cohen. “We will continue to work collaboratively and expeditiously with global regulatory agencies to bring this potential treatment to people living with ALS in accordance with the applicable regulatory approval processes.”
While a Phase 3 trial for AMX0035 has yet to be announced, another Phase 2 trial for the experimental drug is nearing completion. This trial is investigating the safety and neurological effect of AMX0035 on patients with Alzheimer’s disease.
The new study was published in the journal Muscle & Nerve.
Source: Massachusetts General Hospital
