Biogen to seek high-dose Spinraza approval after new data

Nearly eight years after Biogen obtained the initial approval for a spinal muscular atrophy (SMA) drug, the company is now aiming to introduce a new dosing regimen for Spinraza. Recent clinical trial data, unveiled on Tuesday, suggest that a higher dose regimen may enhance outcomes, though the results are not definitive. The study indicates that the higher dose regimen improved motor skills in comparison to a historical sham control group from the original study that led to Spinraza’s 2016 approval.

Currently, Spinraza is administered to SMA patients starting with three 12 mg doses two weeks apart, followed by a 12 mg dose after a month, and then 12 mg maintenance doses every four months. The proposed new regimen more than doubles the dosage with two initial doses of 50 mg two weeks apart, followed by 28 mg maintenance doses every four months.

In September, Biogen announced that the study had met its primary endpoint and that the company planned to seek FDA approval for the new dosing regimen. Stephanie Fradette, Biogen’s head of neuromuscular development, emphasized that the initial goal was to develop a safe and effective therapy for patients with no prior treatment options. "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," she stated.

The key segment of Biogen’s study involved 75 treatment-naïve infantile-onset SMA patients. Fradette explained that while the decreasing number of treatment-naïve patients is a positive trend for the community, it complicates the process of conducting clinical trials. It took 30 months to enroll the pivotal cohort.

On the CHOP-INTEND motor skills test, patients in the high-dose group showed a 15.1-point improvement around six months, compared to an 11.1-point decline in the sham control group, meeting the study’s primary endpoint. However, by day 302, the high-dose group performed numerically worse on the CHOP-INTEND compared to the group receiving the approved 12 mg regimen. Conversely, the high-dose group showed better results on another clinical measure, HINE-2, at approximately 10 months.

Fradette noted that functional measures were “noisier” than survival and biomarker measures, adding that CHOP-INTEND wasn’t designed to directly compare two therapies. She emphasized the need for further discussions to refine these measures and ensure the right evaluation tools are used.

In terms of survival, the high-dose group had a 29.9% lower risk of death or permanent ventilation compared to the 12 mg group, though this result was not statistically significant. The study also assessed neurofilament levels, a potential biomarker for nerve degeneration in SMA. At day 64, the high-dose group showed greater reductions in neurofilament compared to the 12 mg group, but over time, the levels converged as neurofilament fell to very low levels in both groups. By day 183, neurofilament levels in the blood plasma had decreased by 94% from the study’s start in the high-dose group.

Biogen is preparing for regulatory filings, with Fradette indicating that more details will be provided later. The company is collaborating with academic researchers to analyze the data and examine various subgroups. Another segment of the study observed a small group of patients who transitioned from the 12 mg regimen to the high-dose regimen. These patients saw modest improvements in motor function measures HFMSE and RULM, though there was no comparator group for this part of the study.

A significant question remains about the pricing of the higher dose regimen. While Biogen declined to disclose its pricing strategy, TD Cowen analysts suggested it is "unlikely" that the higher dose regimen will be priced above the current one. Spinraza currently has a list price of $142,000 for a 12 mg dose/5 ml vial.