Life or Death: The Fast Track to FDA Approval

Farisa Khan

Associate Editor

Loyola University Chicago School of Law, JD 2024

After five years, the Food and Drug Administration (FDA) has approved a drug for ALS (amyotrophic lateral sclerosis): Relyvrio. While the drug is expected to significantly prolong the life of ALS patients, who typically die within a few years after diagnosis, the fast approval of the drug raises concerns regarding the FDA’s fast-tracking process of approval.

What is ALS?

ALS is a progressive neurodegenerative disease that kills motor neurons in the brain and spinal cord. While the disease has a gradual onset, ultimately the individual loses their ability to speak, move, swallow, eat, and breathe. As a result, most patients with ALS die of respiratory failure or malnourishment within 2-5 years. Furthermore, in 90% of cases, there is no family history or genetic mutation that led to the onset.

Currently, there is no cure for ALS. Approximately 29,000 people are affected in the United States, and 6,000 people die in the U.S. from the disease each year. There are three FDA approved drugs for ALS: (1) Riluzole, the very first drug, approved in 1995. Liquid and an improved pill version were approved in 2018 and 2019; (2) Nuedexta, approved in 2011, which targets specific ALS side effects; and (3) Radicava, approved in 2011 as the second drug put in the market since Riluzole to treat ALS.

What can Relyvrio do for ALS patients?

Recently approved, Relyvrio is a combination of two existing drugs with the goal to prolong life by 5-6 months or more by preventing motor neuron cells from dying. The drug was founded by a small company called Amylix, which focuses on neurodegenerative diseases. While the drug has some side effects, such as abdominal pain and upper respiratory tract infection, the FDA has not considered them significant. Essentially, the drug is Amylix’s first large step towards a cure and treatment for ALS. The President and CEO of the ALS Association stated in an interview that “six months can be someone attending their daughter’s graduation, a wedding, the birth of a child.” For patients facing imminent death, being present for these important milestones is their most important wish.

General requirements for drug approval

For a drug to get approved by the FDA, it needs to receive favorable results from Phase III trials with continued Phase IV monitoring. The studies must be independent and include hundreds of participants to show effectiveness and clear results. The process from Phase I trial to approval can typically take approximately eight years. The stringent requirement and length of time is to assure patients that the drugs they receive are of the highest scientific standard, free of error and unnecessary effects.

How did the FDA approve Relyvrio?

Although the FDA requires positive Phase III trial results, exceptions are made for serious diseases with few treatments. In March of 2022, an advisory panel voted against the drug because there was insufficient data to supports its effectivity. However, six months later, there was a rare second meeting which voted in favor of an accelerated approval. They relied on data from a placebo-based Phase II trial with only 137 patients which resulted in a 25% slower decline. They also relied on an open-label extension study which showed that each of the 90 patients who continued to knowingly take the drug for seven months lived approximately five more months before being hospitalized or dying. Prior to the vote, the director of the FDA’s Office of Neuroscience emphasized the need for increased flexibility when considering a drug that would help those facing certain death. As a result, the FDA only considered results from the Phase II trial with the added requirement of continued monitoring.

Critiques of fast-tracking approval

When the FDA approves drugs through an accelerated process, they require confirmation trials to determine whether the drug was rightly approved and should stay on the market or if the approval needs to be reversed. These trials should be underway during the time of the initial approval. However, studies are not being completed. The implication of this is that many drugs remain on the market and are used without any certainty as to their efficacy. A news report found that 42% of current outstanding confirmatory trials had either not started at all or started a year after approval. Furthermore, the report found that there were 33 studies with completion dates behind schedule, indicating that the FDA is lenient about deadlines in this process.

A concerned Yale professor, who advocated for the fast-track of AIDs medication in 1980s, argued that “the regulatory enforcement is lax” and that “the bargain that was made with accelerated approval is broken in a way that needs serious repair.” This is explained by other critiques who think that drug manufacturers are taking advantage of the accelerated approval process, while the FDA is not doing its part to hold them accountable.

Advantages of accelerated approval

For patients with chronic and life-threatening diseases, accelerated approval can provide great benefits. The process allows new medications and treatments to become available at a faster rate. While there is a risk of drugs being on the market that are not effective, there is also a risk of keeping drugs off the market that could save or prolong a life. Sometimes, this consideration is enough to push the FDA to fast-track approval for a potentially life-altering drugs.

While there are pros and cons to the accelerated approval processes, supporting the FDA’s efforts to fast-track drugs into the market is necessary to ensure that chronically ill patients have every fighting chance to overcome their disease. Whether these patients want to risk taking a drug that has not gone through enough clinical trials or follow the natural progression of their illness to imminent death is a choice that should be left to the patient.