- Biogen will stop work on an experimental ALS drug it's developing with Ionis Pharmaceuticals, announcing Monday that the medicine, dubbed BIIB078, didn't help people with the disease. The treatment was designed for ALS caused by a specific genetic mutation.
- BIIB078 was the second Biogen ALS drug to fail in recent months, after another, called tofersen, missed its primary goal in a late-stage study in patients with a different mutation. Both BIIB078 and tofersen are a type of genetic medicine which could now face larger questions over its use in neurological diseases.
- The setback was disclosed just two days before expert advisers convened by the Food and Drug Administration will review an ALS drug developed by Amylyx Pharmaceuticals. If approved, the drug would join a short list of treatments approved to treat the condition, which causes muscular weakness that typically leads to early death.
A small percentage of ALS cases is linked to genetic mutations, making them a promising target for researchers hoping to halt the course of the disease. Like tofersen before it, BIIB078 is what's known as an "antisense oligonucleotide," which in this case works by disrupting the genetic translation of a mutation to a protein called C9orf72.
In the trial, patients received a spinal infusion of up to either 60 or 90 milligrams of BIIB078, administered across as many as eight doses. Some patients received a placebo. While primarily a safety study, researchers also assessed whether BIIB078 slowed patients' decline as a secondary goal.
Researchers followed trial participants for up to 260 days. Those patients receiving the 60 milligram dose declined at the same rate as placebo patients, while those receiving 90 milligrams declined more quickly, Biogen said. These findings prompted the company to stop development work.
Ionis' Chief Scientific Officer, C. Frank Bennett, said in a statement that the failure suggests C90rf72-driven ALS may be more complex than scientists understand it to be now.
"While these results do not support further development of BIIB078, we anticipate they will provide valuable learnings that lead to a deeper understanding of this form of ALS,” he added.
Biogen and Ionis have had success with another antisense oligonucleotide drug called Spinraza, which treats children with a condition called spinal muscular atrophy, or SMA. But since then, Ionis-invented drugs have faced setbacks in central nervous system diseases, such as the failure of a Roche-partnered drug in Huntington's disease and with the Biogen-partnered tofersen.
In a March 28 note to clients, Stifel analyst Paul Matteis suggested the difference may be linked to how well the drugs reach their targets, with SMA being easier to treat because the affected tissue is in the spine. "To us this raises the question as to whether enough drug is getting delivered to different areas of the brain," he wrote.
He also added that, because children's brains and nervous systems are growing, their tissues can be more easily reconditioned to adapt and recover with a drug intervention.
Following on the heels of Spinraza's success, Biogen in 2018 paid $375 million in cash and bought $625 million worth of Ionis stock for rights to license more antisense drugs from the biotech. With these setbacks, that collaboration hasn't panned out as expected, although it has continued to cost Biogen money in fees paid to Ionis.
Meanwhile, BIIB078's failure adds to a list of setbacks for Biogen's research and development pipeline, increasing the urgency for the company to find success with its approved Alzheimer's disease drug Aduhelm and another experimental Alzheimer's treatment called lecanemab.