Following a review of data from the Phase I STRONG study of the intrathecal (IT) formulation of Novartis’ one-off gene therapy Zolgensma (onasemnogene abeparvovec) in older patients with spinal muscular atrophy (SMA), the Food and Drug Adminstration (FDA) has requested a pivotal Phase III confirmatory study to further support the drug’s regulatory filing;

Sarah Elsayed, Neurology Analyst at GlobalData, a leading data and analytics company, offers her view on the opportunities and challenges in this market:

“Clinical data from the new study are unlikely to be available before 2023. As such, Novartis will suffer further delay in its effort to expand Zolgensma’s patient pool, allowing its direct competitors, Biogen’s Spinraza (nusinersen) and Roche’s Evrysdi (risdiplam), to continue to capture considerable share of the older SMA patients. GlobalData expected that Zolgensma would generate global sales of $2.5bn by 2026, which now looks ambitious given the recent stumbling block.

“Biogen’s first-to-market Spinraza was approved in 2016 by the FDA for the treatment of all sub-types of SMA. It is currently positioned as the market leader with reported global sales of $2.1bn in 2019. Unlike Zolgensma, Spinraza represents a chronic treatment option for SMA patients. Zolgensma, despite costing $2.1m per infusion, is thought to be more cost-effective than Spinraza over the long term as it has the potential of curing the disease and only requires a single administration, compared to Spinraza, which requires patients to be hospitalized multiple times per year in order to deliver the drug through lumbar puncture.

“The FDA’s approval of Roche’s Evrysdi in August 2020, for all subtypes of SMA two months and older, is expected to drive further competition in the market. This new entrant is expected to pose further threats to both marketed drugs, Spinraza and Zolgensma, due to its wider targeted patients, favorable oral dosing and lower annual cost of therapy (ACOT). GlobalData estimates that Evrysdi will reach global sales of $1.8bn by 2026 to equate Spinraza’s sales estimate for the same year. Evrysdi’s expected growth will mainly come at the cost of Spinraza, rather than Zolgensma.

“Although the anticipated delay of Zolgensma’s IT formulation launch will prove costly to Novartis’ expansion plan, the drug still has future prospect to overtake Spinraza’s leadership position considering it is a one-time therapy with potential to replace the defective gene and thereby improve the quality of life of SMA patients.”