Despite possessing a solid data package on the potential of high-dose Sprinraza in spinal muscular atrophy (SMA), Biogen will now need to revise its application if it hopes to secure an FDA nod.
The FDA has handed Biogen a complete response letter (CRL) requesting that the company update “technical information” included in the chemistry, manufacturing and controls portion of its filing for the high-dose regimen of Spinraza (nusinersen), the company said Tuesday.
The FDA’s rejection did not cite any issues with the data on Biogen’s high-dose regimen, the company said. The FDA “provided options for resolution,” Biogen noted, adding that it plans to resubmit its Spinraza filing “promptly.”
“While this outcome was unexpected, we remain committed to bringing the high dose regimen to people living with SMA,” Priya Singhal, M.D., head of development at Biogen, said in a statement. “We are working diligently to provide the necessary information to the FDA.”
In a note to clients, City analysts agreed with Singhal that the snub was “unexpected” but caveated that they believe the issue is a “manageable bump in the road towards approval of higher dose Sprinraza, which shouldn’t take long to ultimately resolve.”
The analyst team said it was “optimistic that Biogen can turn around the CRL in a relatively expedited manner.”
As it stands, Spinraza—first approved for SMA in 2016—is given as three 12-mg starter doses two weeks apart, followed by another 12-mg dose a month after that, at which point patients settle into a 12-mg maintenance regimen every four months. The regimen for the high dose option Biogen is developing starts with two 50-mg starter doses given 14 days apart before patients transition to a 28-mg maintenance dose administered monthly.
Biogen announced it would submit data on high dose Spinraza to global regulators last October, emboldened by positive results from its phase 2/3 Devote trial.
In the Part B portion that study, the higher dose regimen helped significantly improve SMA patients’ mobility as measured by the change from baseline on the Children’s Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTED).
That leg of the trial examined high dose Spinraza in infantile-onset SMA patients, while Part A looked at the safety and tolerability of the increased dose in patients transitioning from the currently approved Spinraza regimen.
Biogen has also released data suggesting higher-dose Spinraza could benefit a range of SMA patients, including those who haven’t been treated previously and those with early- and late-onset disease.
So far, the company has secured a thumbs-up for the high dose Spinraza regimen in Japan. Regulators in the EU are also reviewing the company’s application.
Biogen’s Spinraza rejection comes alongside another production-related SMA snub from the FDA.
Scholar Rock on Tuesday announced that the regulator had turned down the application for its SMA hopeful apitegromab. In that instance, the FDA’s hesitancy came down to findings made during an inspection of a third-party manufacturing site in Indiana, which were not specific to the production of Scholar Rock’s monoclonal antibody candidate.
The facility in question previously belonged to Catalent and was acquired by Danish drugmaker Novo Nordisk last year after its parent, Novo Holdings, purchased Catalent for $16.5 billion. The site has a troubled history and has been implicated in multiple FDA rejections in recent months and years.