US/EU regulators start review of Biogen's high-dose Spinraza

Biogen's treatment for neurodegenerative disorder spinal muscular atrophy (SMA) Spinraza has come under pressure in an increasingly competitive market, but the company hopes a new high-dose formulation could help defend the brand.
The company confirmed today that regulators in the US and Europe have started reviews of a new regimen based on two 50mg doses of Spinraza (nusinersen) given 14 days apart, followed by a higher maintenance dose of 28mg every four months.
The regimen delivers more drug in the first administration than the entire two-month loading phase of the approved Spinraza 12mg regimen, which involves four loading doses.
According to a head-to-head trial called DEVOTE, which underpins the applications, the high-dose slowed neurodegeneration faster at day 64 than the current regimen based on measurements of the neurofilament light chain biomarker.
Moreover, part B of DEVOTE, which enrolled a group of patients who had infantile-onset SMA, met the primary endpoint of change from baseline to six months in the CHOP INTEND scale – which measures motor skills in SMA – compared to an untreated control arm.
That represented a "clinically and statistically significant improvement" over Spinraza 12mg without adding to the side-effect burden, according to Biogen, which has also pointed to trends in the data toward reduced risk of death or permanent need for ventilation.
Spinraza remains a big product for Biogen, but has seen its sales go into reverse as competition in SMA treatment has emerged from Evrysdi (risdiplam), which was approved by the FDA in 2020 and can be delivered orally, as well as Novartis' blockbuster gene therapy Zolgensma, which got a green light in 2019.
Biogen made $1.15 billion from Spinraza in the first nine months of 2024, down nearly 14% on the same period of 2023. For comparison, Evrysdi grew more than 20% to CHF 1.25 billion ($1.38 billion) in the nine months, while Zolgensma rose 4% to $952 million, with additional growth for the latter expected from a recently approved route of administration that will make younger patients eligible for the one-shot treatment.
"Continued progress to improve upon the remarkable initial successes in SMA necessitates an innovative approach," said Thomas Crawford, co-director of the Muscular Dystrophy Association Clinic at Johns Hopkins Medicine.
He added that the new Biogen filing "is a significant step forward for the community."
SMA is a type of motor neuron disease that destroys motor neurons – the muscle-controlling nerve cells – and can be fatal. It affects approximately 1 in 10,000 babies and when untreated is the leading genetic cause of infant mortality.