Despite a PhIII fail, Biogen pushes ALS drug tofersen forward with new analysis in move echoing Aduhelm
In a move reminiscent of its aducanumab development plans, Biogen is taking steps Friday to try to paint a failed Phase III in a positive light — this time for ALS.
The big biopharma released a new analysis combining Phase III data with results from an open-label extension on the Ionis-partnered antisense drug tofersen. Biogen says the drug proved more effective for patients who started taking it earlier in their disease, with the new analysis suggesting a clinical function benefit and longer survival times.
But it remains unclear how persuasive these analyses will be at the FDA, given tofersen did not achieve its primary Phase III goal.
Back in October, Biogen and Ionis reported tofersen did not significantly improve the functional and neurologic decline of patients after 28 weeks of treatment, observing very little difference in response between the drug and placebo groups. The p-value came in at an abysmal p=0.97, equating to a 3% chance that the potential effects seen in the trial were drug-related and not due to chance.
On Friday, however, Biogen said the pooled Phase III and open-label extension data are proof the drug actually works. The companies claimed to see benefits in clinical function, respiratory function, muscle strength and quality of life.
Tofersen is being evaluated in a genetic subset of ALS patients — those with mutations in a gene known as SOD1. The ALS Association estimates that 10% to 20% of patients with family histories of ALS possess such mutations. SOD1-ALS also makes up another 1% to 2% of patients without an ALS family history.
The partners are also arguing that the new data shed light on a potential effect on ALS biomarkers, of which there are none currently proven to be linked. Research to find biomarkers has centered around levels of neurofilament and other proteins, with the theory being that lowering such elements is correlated to a disease-modifying effect.
Here, the companies said the analysis showed reductions in SOD1 and plasma neurofilament both in patients who started taking tofersen earlier and as previously administered. It’s part of the “totality of evidence” Biogen is arguing shows tofersen is more effective the earlier patients receive it.
As Biogen and Ionis approach the FDA with their application, the similarities to the Alzheimer’s drug Aduhelm — and the fiasco that ensued post-approval — abound. In that instance, Biogen halted two Phase III studies early due to futility, but then reversed course and said it saw an effect in one of the trials after more analyses were conducted.
Clarification: This article has been updated to clarify the nature of Biogen’s pooled data analysis.