On 8 January, Biogen announced that the first spinal muscular atrophy (SMA) patient had been treated in its Phase IV RESPOND study evaluating the efficacy and safety of Spinraza (nusinersen) in patients with a suboptimal clinical response to Novartis’ Zolgensma (onasemnogene abeparvovec). RESPOND is a two-year, open-label study that will enrol 60 children up to age three years who have the potential for additional clinical improvement after receiving Zolgensma. There will be two groups in this study. The first group will include 40 infants ages nine months or younger who have two copies of the SMN2 gene and received Zolgensma at ages six months or younger. The second study group will include 20 children ages three years or younger. Participants will receive Spinraza as a 12mg dose that has been split into four loading doses, followed by maintenance doses every four months for the two-year study period.

The study’s primary endpoint will be the total score on the Hammersmith Infant Neurological Examination, and secondary endpoints will include safety, change from baseline on additional motor function measures, other clinical outcomes, and caregiver burden. An additional exploratory endpoint, neurofilament levels, will also be evaluated as a marker of biological disease activity.

Until the FDA’s approval of Zolgensma in May 2019, Biogen’s Spinraza was the only approved treatment for SMA patients. While Zolgensma’s approval expanded the number of treatment options for SMA, there is still an opportunity for other treatment options that can offer benefits such as a favourable route of administration or improved muscle function in SMA patients.

Key opinion leaders (KOLs) interviewed by GlobalData agree that the outcomes with Spinraza are favourable for both patients and their families. However, significant clinical and environmental challenges continue to hinder the wider adoption of this therapy in certain settings. Clinical challenges include the need for a lumbar puncture (LP) each time Spinraza needs to be administered via an intrathecal route. This requires institutional infrastructure and resources for the procedure to be carried out, as well as for post-procedural monitoring of patients. Patients who have undergone spinal fusion procedures for associated spinal deformity have additional difficulty with undergoing an LP, as the procedure could put such patients at a greater risk of injury.

In an effort to address this issue, companies such as Novartis and Roche are developing therapies that have a similar mechanism of action as Spinraza but are intended to be administered via an oral route. Roche’s Evrysdi (risdiplam) was approved by the FDA in July 2020. Evrysdi will face challenges to erode Spinraza’s SMA market share despite its convenient oral dosing due to safety concerns and a lack of long-term data. Novartis’ branaplam is currently in Phase II of development in the US and EU and is expected to be launch in the US in 2024.

The challenge posed by the chronic nature of treatment with Spinraza is expected to be partially offset by Novartis’ gene therapy Zolgensma, which received FDA approval in May 2019 for use in pediatric SMA patients less than two years of age. While the prospect of one-time gene therapy is exciting for patients and physicians, both its price and the lack of long-term safety and efficacy data have hindered its immediate uptake in the market.

GlobalData expects Biogen’s Spinraza to continue maintaining a strong position in the SMA market primarily due to the fact that it will be first to market, as well as patient and physician familiarity. However, it is set to face patent expiration in 2023. Novartis’ recently FDA-approved gene therapy drug, Zolgensma, is also expected to play a pivotal role in the treatment landscape for SMA. However, the high price associated with this one-off therapy means that the company will likely face reimbursement challenges.