Biogen's higher Spinraza dose more effective in Phase II/III trial

A recent study has shown promising results for a higher dose of Spinraza (nusinersen), a drug developed by Biogen to treat spinal muscular atrophy (SMA). This neuromuscular disorder leads to the loss of motor neurons and progressive muscle wasting. The trial, known as the Phase II/III DEVOTE study, successfully met its primary endpoint in a group of infants with SMA.

The DEVOTE study enrolled 145 patients of various ages and SMA types. Among them, 75 treatment-naïve children with infantile-onset SMA constituted the Part B cohort. These children received an investigational higher dose regimen of Spinraza. This regimen involves a quicker loading phase with two 50 mg doses administered 14 days apart, followed by a maintenance dose of 28 mg every four months. In contrast, the approved regimen for Spinraza involves four loading doses given at 14-day intervals and a maintenance dose of 12 mg administered every four months.

After six months, infants receiving the higher dose showed a statistically significant improvement in motor function. This was measured against a predefined, untreated control group from the ENDEAR study, which was one of the pivotal studies supporting regulatory approval for the standard 12 mg dose of Spinraza. Specifically, patients in the higher dose group had an adjusted average difference of 26.19 points in CHOP-INTEND scores compared to the control group. The CHOP-INTEND tool assesses motor function in infants with neuromuscular disorders like SMA.

Secondary outcomes of the study also favored the higher dose of Spinraza, showing a positive trend over the current 12 mg regimen on key biomarker and efficacy measures. Moreover, the higher dose was generally well tolerated by the patients. Adverse events were consistent with those commonly associated with SMA and Spinraza’s known safety profile. Interestingly, serious adverse events were less frequent in the higher dose group, occurring in 60% of cases compared to 72% in the 12 mg group.

Spinraza, an antisense oligonucleotide (ASO), addresses the underlying cause of motor neuron loss by continually increasing the production of full-length survival motor neuron (SMN) protein in the body. The 12 mg dose of Spinraza is already approved in more than 71 countries for treating infants, children, and adults with SMA, a genetic disorder marked by the loss of motor neurons.

Financially, Spinraza generated $1.74 billion in sales for Biogen in 2023. However, sales are projected to decline steadily, reaching $1.13 billion by 2030. The drop in revenues is attributed to shipment timing, competition, and pricing pressures outside the United States, according to Biogen’s 2023 financial report.

Biogen has announced plans to seek regulatory approval for the higher dose regimen of Spinraza. Stephanie Fradette, head of the neuromuscular development unit at Biogen, commented on the findings: “While there has been remarkable progress in the treatment of SMA, there remains significant unmet need. Building on the well-characterized profile of Spinraza established over the past 10 years, we continue to explore the potential for maximizing efficacy outcomes while maintaining our commitment to safety.”

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