- Biogen isn't finished with its clinical efforts to prove the effectiveness of its spinal muscular atrophy treatment Spinraza, announcing this week the launch of a study designed to explore whether higher doses of the drug could deliver greater benefit to patients.
- DEVOTE, as the trial's called, will test doses of Spinraza roughly two times higher than the dosing regimen currently approved by the Food and Drug Administration. Notably, Biogen plans to enroll adults as well as children into the Phase 2/3 study, hinting at the potential the biotech sees in treating older patients.
- While Biogen made no mention of Zolgensma, the recently launched SMA gene therapy from Novartis, competition is likely on the mind of Biogen executives. Approved for infants under two, Zolgensma offers the potential for one-time treatment of the progressive neuromuscular disorder.
Spinraza (nusinersen) was the first drug approved in the U.S. to treat spinal muscular atrophy, an inherited disease caused by mutations in a crucial gene.
In its most severe form, SMA is typically fatal before age two. Individuals with more copies of a "back-up" gene, and thus less severe disease, can reach motor milestones like sitting or walking independently. Those with more than four copies usually walk through adulthood.
Biogen's therapy, delivered by an injection into the spine, alters genetic expression to spur production of functional protein. Clinical data show Spinraza to be effective at improving motor function and extending survival of infants with SMA.
That benefit has turned Spinraza into one of Biogen's most important products, especially as other bets made by the company in Alzheimer's have come up short.
The May approval of Novartis' Zolgensma (onasemnogene abeparvovec) brought with it questions of whether families of infants with SMA would opt for the gene therapy's one-time infusion and chance at long-lasting benefit over Spinraza's thrice-yearly injections.
Biogen executives said recently they haven't seen significant changes.
"So far, it's been slow," Biogen's finance head Jeff Capello told investors at a Sept. 9 conference hosted by Morgan Stanley, referring to Zolgensma's launch.
"We think the market is big enough for multiple therapies," he added, echoing comments from Biogen CEO Michel Vountasos in July.
Still, Biogen is clearly reviewing how well Spinraza can compete.
The trial will compare Spinraza's approved dosing — four loading doses at 12 mg followed by maintenance dosing every four months — with an experimental regimen of two 50 mg loading doses and then 28 mg every four months.
Umer Raffat, an analyst at Evercore ISI, thinks the higher dose could prove more effective in infants as well as in teenagers and adults, writing in a note to clients that Biogen never tested above 12 mg.
In theory, higher dosing is also likely to increase side effects. Raffat noted that some toxicity was seen in preclinical testing in monkeys, but pointed out that the doses given were equivalent to much higher levels in humans that what Biogen is now proposing.
In its statement, Biogen said Spinraza's well-characterized safety profile allowed for further exploration of dosing higher.
The biotech plans to enroll 126 infants and adults into the study, which will include a double-blind, randomized treatment period.
If Biogen can prove higher Spinraza dosing is more effective, it could be better positioned to win over older patients with SMA, for whom Zolgensma is not approved.
Capello noted on a recent earnings call that half of the patients newly starting on Spinraza treatment in the second quarter were adults.
Novartis plans to offer more details on how Zolgensma has performed since approval when it discloses its third-quarter results later this fall.