Novartis has recently announced that the Food and Drug Administration (FDA) has lifted a clinical hold on its spinal muscular atrophy (SMA) drug OAV-101, an intrathecal (IT) formulation of Zolgensma (onasemnogene abeparvovec). Novartis will now be able to initiate a pivotal Phase III trial (STEER) to evaluate OAV-101 IT in treatment-naïve patients with SMA Type 2 aged between two and 18 years old, which, if successful, would greatly increase sales for Novartis due to the high cost of therapy of Zolgensma, says GlobalData, a leading data and analytics company.

Philippa Salter, Neurology Analyst at GlobalData, comments: “Although patients with SMA Type 2 have less severe disease than some other types of SMA, they are still faced with significant challenges. As a one-time gene therapy, Zolgensma would transform treatment for these patients. Novartis will be hoping that positive results seen in earlier clinical trials will be carried through into this pivotal Phase III trial.”

The intravenous (IV) formulation of Zolgensma is only approved in the US for patients under two years of age, so the development of IT Zolgensma would likely more than double the patient population targeted by Novartis, which would have a huge impact on the potential revenue for the drug. However, its high cost of therapy is a significant barrier to the uptake of Zolgensma.

Salter continues: “Zolgensma is currently the most expensive drug available with a price tag of $2.1m. This has led to challenges surrounding reimbursement and therefore its availability for patients. It will be crucial that Zolgensma can demonstrate significant efficacy in the STEER trial, so that its long-term cost-effectiveness as a one-off gene therapy is favourable compared with its competitor Biogen’s Spinraza (nusinersen), which requires patients to be hospitalized multiple times per year every time it is administered. GlobalData estimates that Zolgensma will reach global sales of $1.9bn by 2026. ”

The SMA market is highly competitive and as such, the clinical hold has not just delayed Novartis’ development of Zolgensma, it has also allowed its competitors, Biogen, the current market leader, and Roche’s Evrysdi (risdiplam) to gain traction in the older SMA patient population.

Salter adds: “Evrysdi is a strong competitior to Zolgensma and Spinraza, with its oral route of administration allowing for convenient at-home dosing giving it a strong advantage in the SMA market. Both Spinraza and Zolgensma are administered intrathecally via an invasive lumbar puncture which requires hospitalization. GlobalData estimates that Evrysdi will reach global sales of $2bn by 2026.”