The Food and Drug Administration recently approved the first new drug in more than two decades to treat ALS, the disease more commonly known as Lou Gehrig's disease that attacks and kills the nerves that control muscles.
About 12,000 to 15,000 Americans have ALS, which causes nerves to lose the capability to activate muscles and leads to paralysis, according to the Centers for Disease Control. Most people with ALS die from respiratory failure, usually within three to five years of diagnosis.
The FDA in May approved the use of the drug Radicava to treat ALS after a successful trial in Japan. Riluzole, the only other drug that was available to treat the disease, was approved for use in the United States in 1995.
Dr. Justin Kwan, an assistant professor of neurology at the University of Maryland School of Medicine and co-director of the University of Maryland ALS Clinic at the University of Maryland Medical Center Midtown Campus, explains how Radicava works.
How does Radicava treat ALS?
Radicava has been shown in a clinical study to slow the decline in physical function in people with ALS. It decreases the nerve cell damage that occurs for reasons we don't completely understand. Radicava has been shown to prevent nerve cell death in animal models by decreasing oxidative stress.
How is Radicava different from the drug that is on the market now?
Riluzole and Radicava work completely differently. Riluzole blocks the release of glutamate, which is the message that nerve cells use to communicate with each other in the central nervous system. We believe that excessive glutamate release may cause injury to the neurons, and by blocking its release, we believe that is how riluzole slows down symptom progression in ALS.
What are the benefits of Radicava?
In a randomized placebo study in Japan, Radicava was shown to slow the rate of decline on the ALS functional ratings scale which is how we measure patients' functional status. Patients who received Radicava lost approximately 5 points and patients who received a placebo lost 7.5 points.
Please explain the results of the clinical trial in Japan and how that made it possible for the drug to be offered in the United States?
There are concerns about this study. The people who participated in the study in Japan tended to have less severe disability, tended to be earlier in their disease course, and tended to have slightly slower progression. It is difficult to generalize the findings from this study to the entire group of individuals in the world who have been diagnosed with ALS.
The reason the drug was approved is because the company was able to persuade the FDA that the results were sufficiently robust that it warrants approval.
The drug was approved under the orphan designation. What does that mean?
Orphan drug designation is a specific designation by the FDA. In order for a drug to qualify as an "orphan drug," it must meet certain criteria. The drug must be intended to treat a disease or condition that affects 200,000 or fewer people in the United States, which is categorized as a rare disease. By having orphan status, there are certain financial incentives for the drug development process, which include tax credits or extended patent protection.
Why has it taken 20 years for a new drug to make it to market?
Our understanding of the biology of ALS has improved over the years, but we still don't fully understand what causes the disease, which contributes to the lack of effective drug development. Another reason may be that by the time someone is diagnosed with ALS, he or she has already had a substantial loss in nerve cells, so the drugs that we have tested may be ineffective because the disease has progressed to the extent where it is not possible to treat.
What are some of the side effects of Radicava?
Radicava appears to be safe. Major side effects include bruising, constipation, skin changes, rash, difficulty swallowing and insomnia. Compared to the placebo group in the study, the side effects were essentially no different. We can't say for sure if the side effects were from the drug or not.