As competitive threats escalate for Biogen’s Spinraza (nusinersen), the company has announced a global clinical trial to investigate the drug at higher doses in a broad range of patient subpopulations.

Although not without risk, this strategy is likely to represent Biogen’s best chance of maintaining dominance of the spinal muscular atrophy (SMA) market.

Spinal muscular atrophy treatment

In 2016, Spinraza became the first therapy to receive marketing authorisation for SMA, a rare neurodegenerative disease that primarily affects children. The approval represented a major breakthrough in the field with clinically meaningful improvements in motor function, the achievement of milestones, and survival observed for the first time in children with SMA.

However, Biogen’s monopoly of the SMA market is threatened by the recent approval of Avexis’ Zolgensma (onasemnogene abeparvovec-xioi), a gene therapy administered as a one-time intravenous infusion that is approved for the treatment of children under two years old.

Despite costing $2.1m per infusion, Zolgensma is thought to be more cost-effective than Spinraza over the long term requiring only a single administration. This also makes Zolgensma’s usage much more convenient by comparison to Spinraza, which requires patients to be hospitalised multiple times a year to administer the drug by lumbar puncture.

Biogen is also facing further threats from the pipeline, including from Roche’s risdiplam. The drug is in late-stage development and has a similar mechanism of action to Spinraza, but offers a more convenient oral administration route.

However, Biogen is taking steps to prevent the marginalisation of its leading drug. The DEVOTE trial is a Phase II/III, randomised, controlled, dose-escalating study that is expected to enrol 126 SMA patients of all ages, including adults. The trial will evaluate a new treatment regimen consisting of two loading doses of 50mg Spinraza followed by maintenance doses of 28mg every four months, compared with the current regimen of four loading doses of 12mg Spinraza followed by maintenance doses of 12mg every four months.

Biogen contends the higher dose could result in even greater efficacy results. If realised, this would provide a boost to its marketing campaign and could deter patients from switching to new competitors. However, an obvious risk of increasing the dose so drastically is the potential for new safety signals to emerge, particularly as toxicity was observed in preclinical studies. However, these effects occurred at comparatively higher doses in animals than Biogen is proposing to administer to human subjects.

Furthermore, Biogen’s decision to include patients of all ages in the trial suggests that in the coming years, the company could more aggressively target later-onset patients, a sub-section of the population that is often overlooked. This would further differentiate Spinraza from Zolgensma, which is currently only approved for infantile-onset SMA.

Related reports
GlobalData (2019) Spinal Muscular Atrophy (SMA), Forecast in Asia-Pacific Markets to 2028, to be published