FDA Approves Treatment for Rare Form of ALS

Manuel Balce Ceneta/AP photo

The U.S. Food and Drug Administration (FDA) has approved a drug for treating patients with a rare form of neurological disease called amyotrophic lateral sclerosis (ALS).

ALS affects motor neurons—nerve cells in the brain and spinal cord that control voluntary muscle movements like walking, chewing, breathing, and talking. An individual suffering from ALS loses the ability to activate specific muscles, which eventually causes the muscles to become weak and suffer from paralysis.

The drug “Qalsody,” also called tofersen, has been approved by the FDA for patients with ALS associated with “a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS),” according to an April 25 FDA announcement.

According to the CDC, only fewer than 500 of the 16,000-32,000 ALS patients in the United States have mutations in the SOD1 gene. Qalsody targets the SOD1 mRNA to reduce the synthesis of SOD1 protein.

The FDA approval was based on observing a reduction in plasma neurofilament light (NfL) among SOD1-ALS patients in a test involving 147 individuals. NfL is a blood-based biomarker of axonal injury and neurodegeneration. Axons are a portion of a nerve cell that carries nerve impulses away from the cell body.

The most common adverse effects of the medication include pain, fatigue, muscle pain, joint pain, and increased cerebrospinal fluid white blood cells.

According to the prescription information of the drug, serious events of myelitis and radiculitis have been reported. Myelitis refers to an inflammation of the spinal cord, while radiculitis is the pain that radiates along the nerve and is caused by inflammation at the root of the nerve’s connection to the spinal cord.

Other reported serious events include elevated intracranial pressure, papilledema or swelling in the eyes due to higher intracranial pressure, and Aseptic Meningitis which refers to an illness characterized by serious inflammation of the linings in the brain.

Accelerated Approval, Patient Study

Qalsody was greenlit under the Accelerated Approval Program, which allows the FDA to “approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.”

“To confirm the clinical benefit of Qalsody, a Phase 3 randomized, double-blind, placebo-controlled trial is ongoing in individuals who are carriers of the SOD1 genetic mutation who do not yet have symptoms.”

Under the Accelerated Approval Program, the drug is only given traditional approval after the company’s confirmatory trial shows that the medication offers a clinical benefit. If no such benefit is shown, the FDA can remove the drug from the market.

In the study involving 147 patients, 108 individuals were randomly assigned a treatment of Qalsody or a placebo for a period of 24 weeks.

Those who received Qalsody were found to have “significant reductions” in NfL concentration at week 28 compared to the placebo group. The reduction in NfL was found to be consistent across various subgroups in the study.

Amyotrophic Lateral Sclerosis

As motor neurons in ALS patients degenerate and die off, they cease sending messages to muscles. As a consequence, the muscles start to twitch and waste away. Ultimately, the brain loses its ability to control voluntary movements.

At present, ALS has no known cure. However, medications can slow down the progression of the disease. In addition, therapies can help patients adapt to the physical and emotional changes that occur as a result of ALS.

People who have ALS will eventually be unable to stand, walk, use their hands and arms, or get out of bed. They can have problems with speaking, chewing food and swallowing, and breathing.

Patients usually end up losing the ability to breathe and depend on a ventilator. Most people with ALS tend to die from respiratory failure, typically within three to five years from symptom onset. Around 10 percent of the patients last for a decade or more.