Biogen holds firm on denying compassionate use for experimental ALS drug

Biogen biologics plant in Denmark
The company will provide early access to tofersen only after study participants are no longer taking placebo, wrote Biogen R&D chief, Al Sandrock, in a message posted to the company's website. (Biogen)

Nearly 70,000 people have signed an online petition asking Biogen to provide an experimental ALS drug to a patient requesting it under compassionate use, but the pharma is sticking to its decision not to offer the treatment.

Lisa Stockman Mauriello was diagnosed with amyotrophic lateral sclerosis (ALS), a debilitating, progressive disease that can be terminal in just five years, weeks after enrollment closed for the drug’s phase 3 clinical trial, her husband, Bob Mauriello, told news channel WCNC on Tuesday. Her disease is a genetic form of ALS stemming from a mutation in the SOD1 gene: precisely the kind of ALS Biogen is developing the drug for. Known as tofersen, the drug is an antisense oligonucleotide licensed from Ionis Pharmaceuticals.

“I think there’s evidence to suggest that this therapeutic would be helpful to her… We’re very limited as to what we can offer our patients, so this I feel is her best chance for a therapeutic that could make a meaningful difference in the course of her disease,” Neil Shneider, M.D., Ph.D., told WCNC. Shneider is a neurologist and director of the Eleanor and Lou Gehrig ALS Center at Columbia University and is treating Stockman Mauriello.

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At the heart of Biogen’s denial is the question of broader access. The fastest way to get tofersen to as many patients as possible would be regulatory approval, wrote Biogen chief medical officer, Maha Radhakrishnan, M.D., in a March 17 letter to Stockman Mauriello that she shared with WCNC. That, of course, requires the completion of clinical trials.

“Providing individual access to tofersen at this time could jeopardize access to tofersen for hundreds of SOD1-ALS patients by impeding our ability to complete the study that will determine whether tofersen is efficacious and safe and to seek subsequent regulatory approvals as quickly as possible,” Radhakrishnan wrote.

In other words, it would not be fair to study participants who were randomized to placebo if Biogen were to offer the drug to patients not participating in the study.

The company will provide early access to tofersen only after study participants are no longer taking placebo, wrote Biogen R&D chief, Al Sandrock, M.D., Ph.D. in a message about the experimental treatment posted to the company’s website.

“We cannot overlook these patients when considering questions of broader access, and cannot keep them on placebo while at the same time offering tofersen to those outside of our study,” Sandrock wrote. “Offering tofersen outside of the study would risk failing to complete the study and risk failing to obtain access for all SOD1-ALS patients".

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Sandrock did not mention Stockman Mauriello by name in the letter but started it by conveying “deepest gratitude” to many people who have contacted the company about their “concern for people living with ALS.” A Biogen spokesperson confirmed by email that “the message was written with all those audiences in mind,” namely those who signed Stockman Mauriello’s petition, as well as those who have contacted Biogen about Stockman Mauriello and other patients with ALS.

Tofersen is in a phase 3 study pitting it against placebo in 178 patients with ALS and a SOD1 mutation.

“These patients agreed to participate in our study acknowledging the risk that they may not receive tofersen, and with hope that tofersen could be shown to work and be approved for all patients,” Sandrock wrote.

Biogen expects the study to read out later this year. If the results are positive and the company doesn’t need to carry out more studies, Biogen will “immediately open an Early Access Program for individuals with SOD1-ALS,” Sandrock wrote.

“I agree wholeheartedly that all those in the clinical trials deserve deep gratitude, because they all knowingly accept the risk of being treated with a placebo and also the unknown adverse events that could occur by being treated with an investigational drug,” Stockman Mauriello said in a statement released on Wednesday.

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“But the company is wrong in concluding that the only option available is to ‘open the floodgates’ to the active drug,” she continued. “That simply is not based in either science or humanity, the two tenets that Biogen claims are at the core of its mission… I sympathize with the position that Biogen’s leadership have taken and I understand the desire to focus on the science. But for a disease such as ALS, particularly a form of the disease that kills so quickly, I know that more can be done.”

At the end of the day, Biogen’s decision to deny Stockman Mauriello’s request is about more than just one patient, she wrote.

“[It] is about all those whose circumstances eliminate the possibility of waiting for the scientific process to play out: Whose lives are at stake, whose physicians recommend access and for whom tofersen is the only realistic hope of extending their lives to enjoy just a few more weeks or months with loved ones,” she wrote.

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ALS is a difficult field in which drugs that show early promise can turn out to offer no benefit, or pose “unjustified risks” to patients in later studies. Biogen knows this as well as anyone, having seen its last ALS effort, dexpramipexole, fail in phase 3.

Since then, the company has “rewired” its approach to ALS, switching its focus 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 90% of ALS cases are considered “non-genetic,” Biogen thinks there is an underlying genetic piece to these patients. It hopes to translate the lessons it learns from its work in SOD1 and C9orF72 into other populations, Toby Ferguson, M.D., Ph.D., head of Biogen’s neuromuscular development unit, said in a previous interview.