A Historic Day in Drug Development: AveXis Gene Therapy for SMA Approved

May 27, 2019By Frank J. Sasinowski & James E. Valentine

On May 24, 2019, FDA approved Avexis’s BLA for its gene therapy, Zolgensma (onasemnogene abeparvovec-xioi), for treatment of spinal muscular atrophy (SMA).  This represents the first approval of a systemically-administered somatic gene replacement therapy.  (The first gene therapy approved by FDA was Luxturna in Dec. 2017, which is administered locally as a subretinal injection) (see previous coverage here).  Hyman, Phelps & McNamara, P.C.’s  Frank Sasinowski and James Valentine are honored to have aided AveXis in this development program and approval.

This approval is a monumental milestone in the history of personalized, targeted medicine because NOW these therapies that target the root causes of genetic diseases using gene replacement have a proven path to the market.  This is not to say that all issues related to the development and regulation of gene therapies have been solved, but the Zolgensma approval is a demonstration that these issues can be navigated and the goal post of approval can be reached.

This approval comes on the shoulders of FDA regulators in the Center for Biologics Evaluation and Research (CBER).  CBER director, Dr. Peter Marks, has consistently and strongly encouraged the development of gene therapies, while at the same time, as recently as the April 15th Muscular Dystrophy Association annual scientific meeting, exhorting sponsors to pay keen attention to their manufacturing. CBER officials, and In particular, those in the Office of Tissues and Advanced Therapies (OTAT) which is led by Dr. Wilson Bryan, a neuromuscular expert, deserve acknowledgment for their efforts on both this condition, SMA, and on gene therapies, generally.   As for SMA, OTAT has paid special attention to the Voice of the SMA Patient as witnessed by Dr. Bryan giving opening remarks at the April 18, 2017 externally-led patient focused drug development meeting on SMA, and Dr. Lei Xu, an OTAT neurologist who participated in that meeting.  As for OTAT’s commitment to advancing regulatory science in the arena of gene therapies, Dr. Bryan, for example, at the September 13, 2018 scientific workshop convened by the EveryLife Foundation for Rare Diseases, exhorted gene therapy developers in the rare disease space to employ “efficient development” programs (presentation available here).  One suggestion he noted was for sponsors to “try to hit a home run!” by designing their very first-in-human study to provide evidence of effectiveness because, if it is a home run, it could be the basis for approval.  It is this type of forward-thinking that has allowed the first gene therapies to reach patients in the United States!

All those CBER officials involved in this BLA review, and especially those in the OTAT review team, including Dr. Andrew Bynes, manufacturing review team lead, and Dr. Lei Xu, medical review team lead, worked tirelessly on this and merit special public recognition.

We look forward to contributing to the field of regenerative medicine development.  Prior posts on this topic, including recent FDA guidance documents and policies related to gene therapy, can be found here: