Observational Study of Fertility in Risdiplam-Treated Adult Male Patients With Spinal Muscular Atrophy (SMA)



Poster Number: T392


Travis Dickendesher, PhD, Genentech, Inc, Natan Bar-Chama, MD, Reproductive Medicine Associates of New York / The Mount Sinai Hospital New York NY, Shafeeq Ladha, MD, Gregory W. Fulton ALS and Neuromuscular Disease Center, Barrow Neurological Institute, Taraneh Nazem, Reproductive Medicine Associates of New York, Shereen Yap, Genentech, Inc, Beverly Assman, MLS, Genentech, Inc, Elise Lim, Genentech, Inc, Rushabh Shah, Genentech, Inc, Sheila Shapouri, PharmD, MS, Genentech, Inc.

Risdiplam (EVRYSDI®) is an FDA-approved survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier for pediatric and adult patients with SMA. SMN2 splicing modifier effects on male sperm cell production were identified in animal studies and were reversible after an appropriate length of exposure cessation. The impact of SMN2 splicing modifiers on the human male reproductive system is unclear, as is the impact of SMA.

We describe an observational study to collect patient-reported, fertility-related outcomes in risdiplam-treated adult males with SMA. The primary objective is to assess if adult males with SMA exposed to risdiplam conceive. Exploratory objectives are to characterize (1) confounding factors that may impact fertility; (2) fertility-related healthcare resource utilization, management and fertility treatment decisions; and (3) pregnancy outcomes.

Consenting males with SMA, aged 18–50 years, who have been exposed to risdiplam and are actively trying to conceive or have conceived will be eligible to participate, as will their partner/surrogate/gestational carrier (optional). Participants will complete a questionnaire annually and will be followed for 3 years, until conception occurs, or until they stop trying to conceive. Retrospective data will be collected for those who conceived after risdiplam exposure but before enrollment.
Questionnaire results will be entered into a remote ePlatform (i.e., smartphone application). Demographic information, general health, medical history, SMA treatment, social history, environmental exposures, relationship/sexual history and fertility journey (including testing, treatment, outcomes) will be collected.

This study will provide data on the fertility journey and outcomes for risdiplam-treated males with SMA. In parallel, a second study is evaluating the impact of SMA on male fertility outcomes. These studies will inform on a critical SMA focus area, considering increased family planning ambitions afforded by disease-modifying therapies.