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Biogen, Ionis shelve ALS drug following study failure

Biogen and Ionis Pharmaceuticals are stopping development of an experimental drug for ALS following new clinical trial results that didn’t meet the companies’ expectations.

The trial, which enrolled almost 100 people with the nerve-destroying disorder, found the drug actually worked as intended. Biogen and Ionis had designed it to lower levels of “ataxin-2,” a protein tied to amyotrophic lateral sclerosis, and on that measure it was successful. High-level results released Thursday showed participants who received the drug, named BIIB105, rather than a placebo experienced significant decreases in the protein over a six-month treatment period.

However, the drug didn’t appear to change the trajectory of the disease. It didn’t impact breathing, strength and overall function — key health measures that diminish as ALS progresses. BIIB105 also didn’t substantially reduce a different protein, “neurofilament light chain,” that recently became important across this area of research. Qalsody, another ALS medicine developed by Biogen and Ionis, won marketing approval last year based on its ability to lower that protein.

“While BIIB105 lowered ATXN2 protein, it did not reduce neurofilament, which gives us confidence that BIIB105 did not slow the disease process,” said Stephanie Fradette, head of Biogen’s Neuromuscular Development Unit, in a statement.

In the trial, participants who completed the main six-month treatment period were then offered entry into an “open-label extension” phase, in which they all could receive BIIB105. Biogen and Ionis said data from that phase were similar what was seen earlier in the study, with “sustained reductions” in the ataxin-2 protein but “no impact” on neurofilament or clinical outcome measures.

The companies said there was no evidence that any subgroup of drug-treated patients benefited clinically.

Analysis of the data remains ongoing. Biogen and Ionis plan to present more detailed study results next month at an ALS research convention in Stockholm.

The shelving of BIIB105 is the latest setback for a field of drug development marred by failure. ALS, like many central nervous system disorders, is complex and difficult to combat. Scientists first discovered the disease over a century ago; and yet, just a few medicines have ever been approved to treat it. (The list got even smaller this year, as a once-promising medication from Amylyx Pharmaceuticals is being pulled from the market.)

Approved in April 2023, Qalsody is the newest offering, though it’s for a very small fraction of ALS patients with specific genetic mutations. Biogen and Ionis collaborated on early development of the therapy, using the latter’s antisense oligonucleotide drugmaking technology.

Qalsody essentially gums up the production of an ALS-associated protein called SOD1. The therapy actually failed to hit the central goal of the study that led the Food and Drug Administration to clear it. In that trial, Qalsody wasn’t any better than a placebo at slowing disease progression. It was, however, better at lowering neurofilament light chain — a biological marker of neurological damage.

The FDA’s decision effectively created a new route to approval for ALS drugmakers, who, since the Qalsody decision, have prioritized showing an effect on neurofilament in their clinical tests.

So far, Qalsody is the only clear victory to come out of Biogen and Ionis’ ALS research. In 2022, the partners discontinued another antisense drug, code-named BIIB078, after an early-stage trial disappointed. Also on Thursday, Ionis revealed that Biogen has opted against licensing a drug the companies have been working on for Angelman syndrome, despite results Ionis described as positive.

The longstanding partnership has been fruitful in other areas, though. It’s produced a blockbuster medicine in Spinraza, a treatment for a rare, muscle-wasting illness. And over the past couple years, Biogen has highlighted the potential of another experimental drug, BIIB080, which is in mid-stage testing as a possible treatment for Alzheimer’s disease.