Biogen hasn’t let a phase 3 failure for tofersen hold it back. In fact, the company has used 12-month data to secure priority review status for a new drug application of the amyotrophic lateral sclerosis (ALS) drug.
If approved, the Ionis Pharmaceuticals-partnered prospect would be the first drug to treat a genetic cause of ALS. The FDA has penciled in a decision date of Jan. 25, 2023, with plans to hold an advisory committee meeting for the application.
The regulator's go-ahead is all the more impressive considering that in October 2021, Biogen revealed that the antisense medicine failed to improve the functional status of SOD1-ALS patients compared to placebo after six months, causing the 108-subject study to miss its primary endpoint.
Now, Biogen has used 12-month data from the phase 3 VALOR trial and an open-label extension to show that an earlier initiation of tofersen treatment slowed decline across measures of clinical and respiratory function, strength and quality of life.
Its workaround has been to zero in on changes in biomarkers and trends favoring tofersen in patients with rapid disease progression to make the case for the candidate. If that approach sounds familiar, it’s because the company tried something similar to ensure the controversial approval of its Alzheimer’s disease therapy Aduhelm.
Specifically, Biogen is pointing to the use of neurofilament as a surrogate biomarker that it argues is “reasonably likely” to predict clinical benefit. Neurofilaments are normal proteins found in healthy neurons, which are increased in blood and cerebrospinal fluid when damage has been done to neurons or their axons. They are also a marker of neurodegeneration, with higher levels found to predict more rapid decline in clinical function and shortened survival among patients with ALS.
An analysis of the 12-month data from the failed VALOR study showed that the drug causes a reduction in neurofilaments. This appears to have convinced the FDA, to which Biogen has promised to continue to send data.
The FDA will also have to consider the high level of serious adverse events—reported by over a third (36.5%) of patients in the 12-month data, according to Ionis. Overall, 17% of participants discontinued their treatment as a result of an adverse event, Ionis said.
The most common adverse events were headache, procedural pain, fall, back pain and pain in extremities, said Biogen, which added that most adverse events were mild to moderate in severity. Serious neurologic events, including inflammation of the spinal cord, nerve pain along the spine, aseptic meningitis and intracranial pressure, were reported in 6.7% of participants, the company added.
While the FDA reviews the drug, Biogen will continue its early access program for participants spanning over a dozen countries. An open-label extension and the phase 3 ATLAS study in pre-symptomatic individuals with motor neurone disease and the SOD1 genetic mutation remain ongoing.
The regulator can find it tricky to make a call on ALS treatments. Last month, the FDA notified Amylyx that it was extending its decision date for its drug AMX0035 to review additional data analyses. The therapy was previously voted down by an agency advisory committee in March in a tough vote that followed riveting patient testimony.