An evaluation of onasemnogene abeparvovec for spinal muscular atrophy (SMN1)

ABSTRACT

Introduction

Onasemnogene abeparvovec is the first systemic gene replacement therapy approved by the FDA for any inherited condition and is the second FDA-approved genetic therapy for 5q spinal muscular atrophy.

Areas covered

We discuss the design and preclinical development of onasemnogene abeparvovec, along with clinical trial and real-world data focusing on efficacy and safety.

Expert Opinion

Although onasemnogene abeparvovec is strikingly effective for the treatment of 5q SMA, it is only approved for use under the age of 2 years and there are also two other FDA-approved molecular-based treatments. Many questions remain in terms of treatment selection, possibility of dose optimization, and combinational therapies.

KEYWORDS:

• Gene therapy
• onasemnogene abeparvovec
• spinal muscular atrophy

Article highlights

• Onasemnogene abeparvovec is a systemic gene replacement therapy for spinal muscular atrophy using a viral vector, AA9

• Onasemnogene abeparvovec is safe with appropriate prescreening and follow up for the treatment of spinal muscular atrophy

• Onasemnogene abeparvovec is most effective when treatment is initiated prior to symptom onset

• Even if given when some symptoms are present, onasemnogene abeparvovec can still be efficacious

• Data on long-term safety and its use in combination with other spinal muscular atrophy genetic therapies will be areas of continued research

Additional information

Funding

The clinical trial that led to FDA approval of product was supported by Avexis, Sophia’s Cure, and the Research Institute at Nationwide Children’s Hospital. Long-term follow-up studies were supported by Novartis Therapeutics.