Nearly eight years after securing a historic first approval for a spinal muscular atrophy drug, Biogen is seeking to launch a new dosing regimen of Spinraza.
Clinical trial data unveiled on Tuesday suggest, but don’t definitively show, that a higher dose regimen could improve outcomes compared to the currently approved one. The study reports that the higher dose regimen improved motor skills compared to a historical sham control group taken from the original study that led to Spinraza’s approval in 2016.
Currently, people with the motor neuron disease who take Spinraza start with three 12 mg doses each two weeks apart, followed by a 12 mg dose after a month, and then 12 mg maintenance doses every four months. The new dosing regimen more than doubles the dose patients receive each time: It includes two 50 mg starting doses two weeks apart, followed by 28 mg maintenance doses every four months.
Biogen had announced in September that the study met its primary endpoint and it was planning to seek an FDA approval for the new dosing regimen.
Stephanie Fradette“When we were developing Spinraza in the early days, we were really focused on identifying a safe and effective therapy and getting it to patients that had no treatment options,” Stephanie Fradette, Biogen’s head of neuromuscular development, told Endpoints News. “There was this potential to optimize for benefit, and as time has gone on, that’s only become more clear as we look across the different therapies.”
The pivotal part of Biogen’s study enrolled 75 treatment-naïve infantile-onset SMA patients. Fradette said there were “fewer and fewer treatment-naïve patients, which is a beautiful thing for this community, but makes conducting clinical trials more complicated,” adding that it took 30 months for Biogen to enroll the pivotal cohort.
‘Noisy’ data
On a motor skills test called the CHOP-INTEND, patients in the high-dose group saw their scores improve by 15.1 points at around half a year compared to an 11.1-point decline in the sham group — meeting the primary endpoint for the pivotal portion of the study.
But the high-dose group actually did numerically worse on the CHOP-INTEND than the group randomized to receive the approved 12 mg regimen at day 302, according to the poster presented at the World Muscle Society annual meeting on Tuesday.
Meanwhile, the high-dose group did numerically better on another clinical measure called the HINE-2 at about 10 months.
Fradette said that the functional measures were “noisier” than survival and biomarker measures, noting in particular that the CHOP-INTEND wasn’t designed to compare two therapies to each other. “I think we have to have further conversation across the community about, how do we refine those measures, and how do we ensure that we’re using the right tools in the toolkit?” she said.
In the study, the high-dose group saw a 29.9% lower risk of death or permanent ventilation compared to the 12 mg group, though the result was not statistically significant.
The study also measured neurofilament, a potential biomarker of nerve degeneration in SMA. At day 64, the higher dose group had greater reductions in neurofilament compared to the 12 mg group.
However, the lines converged over time as the level of neurofilament fell very low in both treatment arms. At day 183, neurofilament measured in the blood plasma was down 94% compared to the beginning of the study for the high-dose group.
Biogen is working toward regulatory filings. Fradette said the company will provide additional details down the line. She added that the company is working closely with academic researchers to dissect the data and look at the different subgroups.
Another part of the study looked at a small group of patients who previously were on the 12 mg Spinraza regimen and transitioned to the high dose regimen. There was no comparator for this part of the study, but patients saw small increases in two measures of motor function called the HFMSE and RULM, Biogen reported.
A big question is how Biogen plans to price the higher dose regimen. The company declined to comment on its pricing plan, but TD Cowen analysts said that it was “unlikely” in their view that the higher dose regimen will be priced higher than the currently approved one. Spinraza has a list price of $142,000 for a 12 mg dose/5 ml vial.