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Biogen and Ionis Pharmaceuticals are stopping development of an experimental drug for ALS following new clinical trial results that didnt 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 didnt appear to change the trajectory of the disease. It didnt impact breathing, strength and overall function key health measures that diminish as ALS progresses. BIIB105 also didnt 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 Biogens 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 its for a very small fraction of ALS patients with specific genetic mutations. Biogen and Ionis collaborated on early development of the therapy, using the latters 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 wasnt 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 FDAs 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. Its 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 Alzheimers disease. '

Biogen already signaled a foray into rare disease last year, where CEO Chris Viehbacher said the company has “tremendous commercial capability.” To be a better neuroscience company, Biogen is going to have to diversify—outside of the therapeutic area that has in recent years defined the company. “We always call ourselves a neuroscience company, but the reality of neuroscience is that this is a high-risk area,” CEO Chris Viehbacher said on the drug developer’s first-quarter earnings call Wednesday morning. And so Biogen will be focused on business development outside of the neuroscience arena, which in turn, will support the expensive, lengthy trials required of the beat. “While we remain committed to neuroscience, my personal view is that is not diversified enough for a company of our size,” the CEO said. Biogen already signaled a foray into rare disease last year, where Viehbacher said the company has “tremendous commercial capability.” Thanks to the slow buildout of Leqembi in Alzheimer’s disease, Biogen knows a thing or two about launching medicines in difficult areas where diagnosis is a challenge and hurdles with payers are rampant. Viehbacher also sees further potential for expansion in multiple sclerosis. “We are very well placed in neurology … but the reality is that we sit there with programs that are very difficult to predict, very expensive, very long-running. And when you actually look at the ability to do external deals, that field is also very narrow. There's just not that many people working in the CNS space,” Viehbacher said. “So we're by no means abandoning it. The fact that we go after these really tough diseases is really a source of pride within Biogen.” He continued: “But the reality is we need to have more predictable results out of R&D.” Biogen's industry peers have found plenty to buy in the space. Bristol Myers Squibb bought Karuna Therapeutics and its schizophrenia med KarXT for $14 billion while AbbVie picked up CNS-focused Cerevel Therapeutics for $8.7 billion, all at the end of 2023.  Speaking of deals, Biogen is unlikely to take on a huge acquisition this year, given the company’s balance sheet, the CEO said. “If something really extraordinary came along, you’d look at it,” he said. Chief Financial Officer Michael McDonnell said the balance sheet is “in a very good spot” in terms of net debt for the first quarter. He says there’s about $4 billion to $5 billion to play with for an acquisition target. In 2025 or beyond, that number could grow. As for the pipeline, the executives had little to report with respect to concrete data, but Viehbacher promised more to come as three key readouts draw closer. A big one is Biogen’s anti-tau agent for Alzheimer’s disease called BIIB080, followed by phase 3 assets dapirolizumab pegol and litifilimab, both for systemic lupus erythematosus. Biogen has developed some tough go-no-go criteria to ensure those programs are only advanced if they prove promising, said Priya Singhal, M.D., head of development. “I think the next job is really now to build out the pipeline,” Viehbacher said. “We want to diversify our business a little bit more than we have in the past.”