Staff at the U.S. Food and Drug Administration said Monday that Biogen’s experimental ALS drug could provide “clinical profit” for a rare and aggressive form of the disease, despite the failure of a larger, late-stage clinical trial last 12 months.
Employees drew conclusions in information documents ahead of Wednesday’s meeting where a panel of external advisors will discuss whether to recommend accelerated approval of Biogen tofersen for the treatment of a rare, genetic form of amyotrophic lateral sclerosis, or ALS. Accelerated approval by the FDA is meant to permit faster approval of drugs for serious conditions that address an unmet medical need.
The panel will examine the mixed evidence from the study regarding the efficacy and safety of tofersen and can vote on whether it shows whether the drug will provide clinical profit in patients with a rare form of ALS. The FDA often follows the advice of its advisory committees, but shouldn’t be obligated to accomplish that.
“That is a situation where there may be a negative clinical trial that didn’t show a statistically significant treatment effect in the specified population of the primary evaluation,” reads the 68-page staff report. Nonetheless, he notes that the study was limited in its ability to find out whether the drug had any effect on the entire population because of the way it was designed. At the same time, the data indicate that targeted use of the drug reduces “a biomarker that has been shown to be correlated with disease progression and prognosis in patients with ALS.”
A separate exploratory evaluation of the drug suggests “clinical profit with longer duration of treatment,” the staff wrote.
If approved, Biogen could turn into the first drug to focus on the genetic cause of ALS, commonly generally known as Lou Gehrig’s disease, which generally affects people between the ages of 40 and 70. It’s a progressive and fatal neuromuscular disease that causes the breakdown of nerve cells in the spinal cord and brain over time. It might probably cause muscle twitching and spasms, significantly impairs motor skills and results in problems with swallowing, respiratory, and ultimately causes paralysis and death.
FDA accepted Biogen’s application for full approval of the tofersen in July. In October last 12 months, the agency prolonged his opinion application for three months. The ultimate decision can be made on April 25.
The FDA review of tofersen comes as Biogen tries to recuperate from the aftermath polarization approval and the disastrous introduction of Alzheimer’s therapy last 12 months. Push for tofersen approval may include its own hurdles: In accordance with results, drug didn’t slow ALS progression in phase three trial announced in October.
But Biogen noted that the study drug affected a mutant version of a protein called SOD1. The protein can accumulate to toxic levels in individuals with mutations in a particular gene, which might damage the nervous system and result in the development of ALS.
In accordance with Biogen, there are only a few thousand people in the world who have been diagnosed with this sort of mutation – about 2% of the 168,000 ALS victims worldwide. In United States, 330 people are affected by the SOD1 mutation. But the approval of the drug could herald a recent area of promising research targeting the cause of ALS, which affects about 5,000 recent people in the United States every year. Researchers at the National Institutes of Health estimate that the number of ALS cases worldwide will increase by nearly 70% to around 376,000.
The study showed that patients who received tofersen had SOD1 protein levels decreased by 26% to 38% compared with patients who received a placebo. Tofersen was also found to lower levels of a protein called neurofilament lumen (NfL), which is “correlated with disease severity, rate of disease progression, and survival in ALS patients,” in line with FDA staff.
The staff highlighted the “convincing reductions” present in the tofersen efficacy data, saying that “such a reduction in neuronal damage, as evidenced by a reduction in NfL, may very well be expected to guide to a slower clinical decline in function.”
The FDA said it was looking for input from the advisory panel on the strength of the efficacy data, and outlined two potential scenarios for the panel to contemplate. The primary is to maneuver forward with a advice for accelerated approval based on Tofersen’s NfL reduction in ALS patients. The second scenario is a advice to totally register the drug based on available data and test results ongoing extension study on tofersen.
ALS Association earlier this month he said he made comments to the FDA’s advisory panel, urging them to recommend full approval of tofersen. The organization noted that the drug meets all requirements for accelerated approval, an FDA designation that allows the agency to approve drugs as quickly as possible.
“SOD1-associated ALS is a particularly rare and aggressive form of an already rare and debilitating disease,” said Dr. Neil Thakur, chief mission officer of the ALS Association. “Recognizing the urgent need for recent treatments for ALS, and based on the data available at this stage, we imagine that tofersen meets all the conditions required for accelerated approval: treating a serious condition, providing a significant advantage over existing therapies, and demonstrating an effect on a surrogate marker that is extremely prone to be will predict a clinical profit.”