The Use of Real-World Data to Support the Assessment of the Benefit and Risk of a Medicine to Treat Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disease that affects individuals with a broad age range and spectrum of disease severity, characterized by progressive loss of spinal motor neurons leading to debilitating and sometimes fatal muscle weakness. Therapeutic options had been limited for this patient population, and to address this unmet medical need, a series of studies on risdiplam (EVRYSDI®) began in 2016. Risdiplam has now been approved in more than 90 countries, including the United States and EU for the treatment of SMA. The approvals were primarily based on two pivotal clinical studies, FIREFISH and SUNFISH, designed to represent a broad spectrum of people living with SMA. FIREFISH is an open-label, single-arm study in infants aged 1–7 months with type 1 SMA. SUNFISH is a randomized, double-blind, placebo-controlled study in patients aged 2–25 years with type 2 and 3 SMA. Real-world data (RWD) from a combination of peer-reviewed publications and individual patients were used to support data interpretation and registration. Natural history data from publications were used to define performance criteria for key clinical endpoints in FIREFISH. RWD from individual patients were also used to perform a robust statistical comparison and contextualize the results from SUNFISH. In this chapter, we present a case study describing how RWD from publications and individual patient data were used to support the development of risdiplam, a medicine to treat SMA.