After months of holding its ground on not offering an experimental ALS drug to patients outside of clinical trials, Biogen is laying out a plan to do just that.
The treatment, tofersen, is in a phase 3 study in 178 patients with amyotrophic lateral sclerosis (ALS) stemming from mutations in the SOD1 gene. After talking it over with regulators, clinical trial investigators, ethicists and patient advocates, the company will now offer tofersen to patients with this form of ALS starting in mid-July, the company wrote in a letter to the ALS community.
In the two-part program, Biogen will begin with the patients whose disease is worsening the fastest in mid-July, after the study participants currently on placebo switch to tofersen but before the drug is shown to be safe and effective.
Later, if the drug proves safe and effective when the study reads out, the company will offer the drug to the broader population of patients with SOD1-ALS under an Early Access Program. The company hopes to roll out the latter part of the program in the fall.
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Despite the new plan to get tofersen to patients before the drug is approved, July may be too late for Lisa Stockman Mauriello, a patient with SOD1-ALS who has been petitioning the company to provide her the drug under compassionate use.
"We are pleased our efforts have contributed to some people with ALS getting access to tofersen faster than they would have otherwise. Unfortunately, it still falls short for SOD1 ALS A5V patients like me who are deteriorating rapidly," Stockman Mauriello wrote in a statement released on Tuesday. "For us, this is a death sentence because we likely will not make it to mid-July when the tofersen Expanded Access trial will start, and if we do, we will be in such bad shape that we may not see any benefit."
Biogen denied Stockman Mauriello's fifth request for expanded access to tofersen on Monday, she said in the statement. That was one day before the company published its letter to the ALS community.
In March, the company reiterated its decision not to provide the drug, tofersen, to patients requesting it under compassionate use. Doing so would be unfair to patients still getting placebo in its phase 3 study, Biogen R&D chief Al Sandrock, M.D., Ph.D. wrote at the time. What’s more, it could jeopardize the completion of the study, delaying its regulatory filing and “risk failing to obtain access for all SOD1-ALS patients,” he wrote.
The company would provide early access to the drug only after study participants switched from placebo to tofersen, Sandrock wrote in March. If the study turned out a success, Biogen would “immediately open an Early Access Program” for patients with SOD1-ALS, he wrote.
Besides those rough timelines, Sandrock didn’t provide further details on that plan.
To allay ethical concerns, Stockman Mauriello proposed in her request that she and patients like her be randomized to receive either tofersen or placebo, just like the participants in the phase 3 study.
"This would have given me, and others, the same 67% chance of getting the medicine that we so desperately need. Then in mid-July, when the trial participants that are getting the placebo are switched over to tofersen, those of us who are receiving the placebo through Expanded Access could also be switched over," she wrote.
"It’s not as if Expanded Access is new. It started in the late 1980’s to help those dying of AIDS and continues to be offered today to help people with cancer. On the FDA website they cite more than 10,000 cases of Expanded Access so any ethical argument rings hollow," she continued.
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Biogen ended its letter with a reminder that “promising drugs can fail in Phase 3 studies,” an experience it’s had firsthand in the ALS space with its last effort, dexpramipexole. After that failure, the company switched from drugs with specific mechanisms, like anti-inflammatories, to medicines like tofersen that target genetic mutations. Behind tofersen, Biogen has two other ALS programs: an Ionis-partnered antisense drug that targets mutations in the C9orF72 gene, as well as a drug that blocks the protein exportin 1 (XPO1).
Although the vast majority of ALS cases are considered “non-genetic,” Biogen hopes to translate what it learns from its work in SOD1 and C9orF72 into other types of ALS, Toby Ferguson, M.D., Ph.D., head of Biogen’s neuromuscular development unit, said in a previous interview.
Editor's note: This story has been updated with new comments from Lisa Stockman Mauriello.