Although a public corporation used poor study design and manipulated data in a small study (Phase II) that found no benefit of the drug, and that truncated needed efficacy studies (Phase III), Relyvrio was approved in 2022 by physicians at the FDA to treat ALS. Now that efficacy studies (Phase III) have been performed in 2024, the company has pulled the drug because no benefit was measured. Much money has been wasted following approval of this drug, money that could have been used for things that provide benefit and for finding therapeutics that really work.
The Continued Failure of Drug Development for Neurodegenerative Disorders
Amylyx Pharmaceuticals announced today that it has begun the process of voluntarily withdrawing its ALS drug, Relyvrio, from the market after it failed to prove efficacy in a large Phase III clinical trial. On the positive side, Relyvrio is a form of a short chain fatty acid called butyrate and was found to cause, as would be expected, few negative side effects. The bad news is it didn’t work, but was approved anyway, leading to years of wasted money and false promises to those who are suffering from a deadly disease.
So why was this lousy drug approved by physicians at the FDA?
Physicians, not scientists, run the FDA. Physicians make many decisions that are not scientifically sound. As scientists have published, “There is ample evidence that many clinical decisions made by physicians are inconsistent with current and generally accepted evidence.” Doing things that don’t work is rampant in medicine, but those things they do make the physicians big bucks. Further, many of the physicians have conflicts of interest. They make most of their money working for the very pharma corporations that they have been tasked to regulate. And the physicians and phamra companies use tricks to avoid conflict of interest regulations. What could go wrong?
Here’s what happened at the FDA as physicians decided to approve this drug that didn’t work. As the FDA viewed it, there were a number of problems with the small trial used to approve Relyvrio. Patients recruited into the trial had been told that they might experience gastrointestinal side effects if they had been assigned the drug, so they could have guessed if they were getting the real thing or a placebo. In a trial that relied on self-reported measures, instead of more objective measures, blinding the patients is critical. Patients used the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), a self-reported data scale that measures motor impairment and functional deterioration in people with amyotrophic lateral sclerosis (ALS)
Confounding the study design were potential “baseline imbalances,” especially during the trial’s extension because those who switched from the placebo to the drug were, on average, healthier than those who had dropped out along the way, which might have exaggerated the ostensible effects. Also, some of the study’s outcomes were compared with “external” control, which were data from patients in previous decades, when the general standard of care was lower. Importantly, the FDA had proposed one method of statistical analysis, but Amylyx had elected to use an alternative method. When the FDA subjected Amylyx’s data to its own test, the results were no longer statistically significant.
The FDA was reluctant to accept the apparent five-month survival benefit, which it regarded as the result of a statistical fishing expedition. So in a small study that was designed to test safety, not efficacy, the drug was approved. This unscientific nonsense is occurring at high rate in the US, and you’re paying for it.
A New Methodology for Treating Neurodegenerative Disorders
I developed a therapeutic strategy and technology, called a systems therapeutic, where a multitude of molecules are used together, to renormalize physiology. I’ve published how to use this strategy to successfully treat ALS, and in vitro data provide evidence that this methodology may work. My strategy is even likely to benefit the development of vaccines. It’s a new paradigm in therapeutic development, very safe, and hopefully one day I can help to diminish the unscientific nonsense in drug development and move forward with an FDA approval for this new paradigm. My paradigm can also use one molecule as the therapeutic, a molecules that activates multiple targets. All diseases involve multiple pathways and therefore therapeutics need to target those multiple pathways. Most current drugs don’t this – unfortunately. We found this strategy worked to rescue degenerating retinal ganglion cells (neurons) in a model of glaucoma. We activated a number of normal physiological pathways using one drug candidate to rescue the neurons. Paradigm shifts aren’t easy and they require much time. I persist.
Stem Cells, Health, Technology 