Another Biogen-Ionis collab hits the dust after phase 1 ALS flop

Biogen and Ionis Pharmaceuticals are packing up and moving on after another antisense ALS candidate flopped in the clinic, less than six months after tofersen, a different med from the same two companies, failed to improve symptoms for the rare and elusive neuromuscular disease. 

The partners said the drug, BIIB078, didn’t improve symptoms at all in a phase 1 trial, according to a Monday announcement. Among the higher 90 mg dose group, patients actually declined quicker than placebo. As a result of the disappointing data, the two companies called it quits on the program. 

Ionis' Chief Scientific Officer C. Frank Bennett said that BIIB078 was designed to tackle the root cause of C9orf72-associated ALS, which is associated with problems with the c9orf72 gene. 

“Unfortunately, this phase 1 study did not support the hypothesis, suggesting that the disease mechanism is much more complex," Bennett said in a statement.

The study recruited 106 trial participants with C9orf72-gene-associated ALS and divided them into six treatment cohorts, with a 3-to-1, treatment-to-placebo ratio in each cohort. The primary measurement was safety and tolerability, while secondary assessments were an assortment of measures of disease improvement. 

The results are yet another disappointment for both companies, but particularly Biogen, which is struggling under the weight of its approved Alzheimer's disease treatment Aduhelm. The companies also saw the failure of a different ALS candidate, tofersen, when the therapy failed to improve symptoms in a phase 3 trial late last year.

Biogen plucked tofersen from Ionis in 2018, months after the two extended a collaboration to develop a suite of programs aimed at neurological disorders. That collaboration extension, announced in April 2018, cost Biogen $1 billion in cash in exchange for the rights to select from a list of neurological targets to develop on its own. Unfortunately, the clinic is where these targets have evidently met their maker. 

Multiple analysts worried that Biogen’s inability to make progress in ALS in recent months ultimately puts more pressure on other areas of the pharma's pipeline, particularly Aduhelm. The drug received accelerated approval from the FDA, relying on cloudy clinical data built on amyloid plaque biomarker evidence. 

With so much now riding on Aduhelm, RBC Capital Markets said that any further failure in the Alzheimer's program could spark a takeover. The team at Jefferies was even blunter, saying BIIB078 had been expected to fail and investors are unlikely "to care too much at this point” about the company’s remaining ALS pipeline. 

Looming for Biogen is a final decision to the Center for Medicare and Medicaid Services’ earlier coverage determination for Aduhelm, which limited coverage only to individuals who were participating in qualified clinical trials. Even if the agency were to reverse the decision, which RBC said could potentially boost access and uptake, Jefferies noted that the action would likely be more valuable for companies like Eli Lilly or Roche's Genentech, which each have their own Alzheimer’s drugs coming down the pike.

As for Biogen’s partner in crime, Ionis, it’s a tough pill to swallow but one the company can likely financially handle given the breadth of its partnerships. In December 2021, the company shipped off an antisense therapy for ATTR amyloidosis, eplontersen, to AstraZeneca in a deal worth up to $2.9 billion. 

Validating analysts’ assessment that Monday’s results were expected, shares for both Biogen and Ionis were stagnant as of the time of publishing.