The U.S. Food and Drug Administration (FDA) recently approved the first new amyotrophic lateral sclerosis (ALS) drug in five years, offering the approximately 31,000 adult patients in the United States and their health care teams another tool that may slow down the disease and extend lives.

ALS, also known as Lou Gehrig’s disease, is an incurable illness that slowly destroys the motor nerve cells in the brain and spinal cord needed for voluntary movement. Over time, people with ALS are no longer able to move, talk, swallow and breathe. There is no cure, and 80 percent of people with the disease die within two to five years of diagnosis.

Relyvrio, the new drug, “is a huge achievement,” says Kelly Graham Gwathmey, M.D., chair of the neuromuscular division and an associate professor of neurology in the VCU School of Medicine. Gwathmey leads the VCU Health ALS Clinic. She talked with VCU Health News about the new treatment option and clinical trials.

The FDA has just approved the first new treatment option for patients with ALS in five years, Relyvrio. How significant is this FDA approval for patients with an ALS diagnosis?

It is a huge achievement for our ALS patients and community. ALS is a rapidly progressive, fatal neurodegenerative disease with an average life expectancy of only two to five years. Our first drug, riluzole, was FDA-approved in 1995, and our second drug, edaravone, was approved in 2017.

Having a third drug on the market allows us to combine therapeutics with differing mechanism of action that likely have a synergistic benefit. This “cocktail” approach will translate to improved patient outcomes in terms of slowed progression and survival.

What is the standard ALS treatment today?

The standard treatment approach today is multifaceted. It involves the patient’s participation in a multidisciplinary ALS clinic, which we know extends life and the quality of it. It also includes the use of ALS-specific medications to slow disease progression. Then, there is symptom management to address excessive secretions, uncontrolled crying or laughing, and constipation, for example.

How does the new drug work?

ALS affects the nerve cells that control voluntary muscle movement. As the disease progresses, organelles within nerve cells begin to lose their function, causing the cells to deteriorate and ultimately die. The new drug works by blocking the molecular processes that cause dysfunction within two organelles, the mitochondria and endoplasmic reticulum. Clinical trials have shown that this helps protect nerve cells from dying.

Who is eligible to receive it? 

The drug is FDA-approved for ALS treatment. We hope that all patients, regardless of disease stage, will be able to access and benefit from the drug. Often, however, insurance payers will set their own criteria for patient eligibility.

During reviews of the drug, the FDA expressed concerns about the medication’s effectiveness. What would you say to patients concerned about the safety and effectiveness of Relyvrio? 

In terms of effectiveness, we have excellent Phase 2 clinical trial data. It showed the functional decline in patients treated with Relyvrio was significantly slower compared to those taking a placebo.

We also believe that Relvyrio has a survival advantage of close to ten months, which is longer than other drugs we have. Because the average life expectancy of someone diagnosed with ALS is about two-and-a-half years, an almost ten-month survival benefit is huge.

The safety of the drug was well studied. The most common side effects are gastrointestinal. Only a small number of patients in the Centaur clinical trial stopped taking the drug because of these side effects.

What is VCU Health doing in the research space related to ALS? 

The VCU Health ALS Clinic has a robust and growing research program. We are actually a site for Relyvrio’s phase 3 clinical trial, a double-blind randomized study where adult patients will get either Relvyrio or a placebo to study its efficacy. Enrollment for this trial is closed.

We are actively enrolling patients for two clinical trials at this time.

• The first one studies Reldesemtiv, a type of fast skeletal muscle troponin activator that aims to slow the decline of muscle function in patients with ALS.
• The second study looks at trehalose, a drug that has preserved motor neurons and motor function. We are part of the Healey Platform Trial for this study, which allows researchers to test several promising ALS therapies in parallel under one master clinical trial protocol. This means more access to clinical trials, more options for patients and finding effective treatments sooner than in traditional clinical trials.

We are getting ready to pilot a Rapid Access ALS Program that includes educating community providers on the signs and symptoms of ALS. We will provide them the resources necessary to refer patients right away for consultation with an ALS specialist. I hope that this will result in earlier diagnosis and access to life-prolonging treatments.