Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig’s Disease) is a uniformly fatal disease that attacks the nerves that control all of the muscles in the body.  Patients diagnosed with this disease slowly lose the use of their muscles, including those that are needed to breathe, and die on average two to five years after being diagnosed.  

In 2013, two undergraduates at Brown University concocted a pharmaceutical (they called it Amylyx) that they hoped would help patients with Alzheimer’s and Parkinson’s.  It consisted of a drug that included an acid found in bear bile, a mainstain of Chinese medicine.  They knew little of what it takes to test a drug and bring it to market, but they found a prominent researcher who thought that a trial for patients was warranted–only for ALS, not for the other two neurological afflictions.  The students pivoted to focus on ALS, and the researcher had the wherewithal to conduct a clinical trial of the novel drug. 

A small trial appeared to show that patients who got the drug lived, on average, five months longer than those who got placebo.Patients, and their advocates, jumped all over this and importuned the Food and Drug Administration (FDA) to approve the drug.

Enter the FDA

The FDA found the clinical trial wanting and declined to approve the drug.  It felt the trial was poorly designed and that the statistical analysis was convoluted to the point of obscurity.  This resulted in a fusillade of criticism that centered on the FDA’s apparent reluctance to approve drugs that showed promise, but were unproved by standard clinical trials.
ALS Advocacy groups had learned a lot from the HIV/AIDs advocacy groups in the 1980s.  In fact, the ALS people capitalized on the experience of these groups to learn how to pressure Congress and regulatory agencies for approval of drugs.  These lobbying efforts often force science to take a back seat to promotion efforts straight out of marketing curricula.  

Eventually, FDA was pressured into bestowing an “accelerated-approval pathway” for Amylyx.  This is a way to legalize pharmaceuticals pending definite proof of effectiveness.  Large trials for the ALS drug are ongoing in Europe.  

In the meantime, sales of the drug have skyrocketed and today sales of the Amylyx will reach $400 million per year.  The drug costs  privately insured patients $158,000 per year, typically with a copay of $30,000.  People on Medicare and Medicaid are expected to pay the whole freight.  Regardless, few people can afford the drug, and, like so much in America, the poor stand to lose out.

Conflicting Interests

Patients with ALS are desperate.  Many feel that the FDA has prioritized science over compassion.  The FDA’s mission, on the other hand, is to ensure the safety and efficacy of the drugs available to Americans.  The FDA suspects that Amylyx has gained currency through emotional appeal of afflicted patients and a transcendently good marketing campaign.  Patients, and their advocates, on the other hand, are determined to try anything that may extend their lives, regardless of the science. 

And then there is the proprietary interest of the company that manufacturers the drug.  Once definitive studies are completed, will the company simply withdraw the drug as promised if it is shown not to work?  Insurers are also enmeshed in the situation:  They legitimately do not want to pay for drugs that have not been proven to work.

Commentary

This blog entry springs from a recent article in The New Yorker.  The piece does not state whether the Brown undergraduates had any scientific background, but it does say that they had no idea how to navigate the drug approval process.  Then they stumbled upon a researcher in ALS who became interested in the drug, but not for dementia and Parkinson’s for which it was originally created.  It was like, what the hell, let’s try it for ALS.  All three diseases have completely different pathophysiology (the process that causes diseases), and therefore it stands to reason that effective drugs would differ for each condition.  But no, trials proceed, drug sales are in the multi millions, and science lies in the wake.  And skeptics fear that ALS patients are being victimized (some say “robbed”), perhaps at the expense of “legitimate” science.  The fear is that patients on Amylyx will forgo participating in important trials of drugs for ALS that are the product of scientific based research.

All parties in this situation have understandable goals.  Patients are desperate and are willing to try anything that holds a shred of promise.  The FDA’s mission is to help ensure the safety and effectiveness of pharmaceuticals, and it feels political pressure diverts it from this mission.  Putting emotion into the approval process is beguiling, but it can be ultimately counterproductive and harmful.