Fertility in Risdiplam-Treated Adult Males with Spinal Muscular Atrophy (SMA): the MARLIN study

Topic:

Other

Poster Number: 236 M

Author(s):

Sheila Shapouri, PharmD, MS, Genentech, Inc., South San Francisco, CA, USA, Sheila Seleri, MD, PhD, Genentech, a member of the Roche group, Natan Bar-Chama, MD, The Center for Male Reproductive Health, Reproductive Medicine Associates of New York, New York, NY, Shafeeq Ladha, MD, Gregory W. Fulton ALS and Neuromuscular Disease Center, Barrow Neurological Institute, Phoenix, AZ, Shereen Yap, MSc, Genentech, Inc., South San Francisco, CA, USA, Elise Lim, PhD, Genentech, Inc., South San Francisco, CA, USA, Rushabh Shah, PharmD, MBA, Genentech, Inc., South San Francisco, CA, USA, Travis Dickendesher, PhD, Genentech, Inc., South San Francisco, CA, USA

Background
SMA is a genetic, progressive neuromuscular disease. Risdiplam (EVRYSDI®) is an orally-administered survival of motor neuron 2 pre-mRNA splicing modifier approved by the U.S. Food and Drug Administration for the treatment of pediatric and adult individuals with SMA. Based on animal studies, male fertility may be compromised with risdiplam treatment. Therefore, understanding the effects of risdiplam on the fertility journey of males with SMA is important for clinical decision-making given increasing family planning ambitions afforded by disease-modifying therapies (DMTs). The ongoing MARLIN study collects and describes fertility-related outcomes in adult males with SMA who have received risdiplam.

Objective
To characterize the fertility journey and outcomes in adult males with SMA who are taking or have taken risdiplam and are actively attempting to conceive or who have conceived.

Results
Baseline data (cut-off: 9/22/2025) in four men with SMA (Type 2, n=2; Type 3, n=2) and their female partners are presented. The mean (SD) age of the men was 36.0 years (3.2). All men were taking risdiplam, with one having stopped treatment for >1 month in the past. Two of the four couples conceived (one spontaneously and one via fertility treatment) while the men were on risdiplam treatment; both resulted in pregnancies that led to full-term live births, with no additional pregnancies reported in this cohort to date.

Conclusions
Initial results from the MARLIN study provide evidence directly addressing patient and clinician concerns about fertility while on risdiplam. This evidence is vital for future family planning discussions among patients and clinicians in the era of effective DMTs.