AVXS-101, Now Zolgensma, Has BLA Accepted By FDA for SMA Type 1


Regulatory action is expected to be made by May 2019. The therapy previously received a Breakthrough Therapy designation from the FDA.

Dr David Lennon

David Lennon, PhD, the president of AveXis

David Lennon, PhD

Novartis has announced that the FDA has accepted its filing of a Biologics License Application (BLA) for its investigational gene replacement therapy, AVXS-101, which is intended to treat spinal muscular atrophy (SMA) type 1.1

The therapy, now known as Zolgensma (onasemnogene abeparvovec-xxxx) is designed to address the genetic root of the condition, which has very few options available to patients. Previously, it received a Breakthrough Therapy designation from the FDA and has now been given Priority Review, with a regulatory decision expected by May 2019.

"This important step by the FDA brings us ever closer to delivering Zolgensma to patients with SMA Type 1,” said David Lennon, PhD, the president of AveXis, the Novartis company which manufactures the therapy, in a statement. “Babies affected by this rare disease are currently faced with debilitating disease progression and lifelong invasive chronic treatment. As a one-time infusion that addresses the genetic root cause of SMA without the need for repeat dosing, Zolgensma represents a potentially significant therapeutic advance for these patients and their families,"

The submission is largely supported by the phase 1 study, START (NCT02122952), which showed that a single intravenous infusion of the therapy in 15 patients with SMA1 resulted in longer survival, superior achievement of milestones of motor function, and better motor function compared to historical data.2 In that trial, 12 patients received the full 2.0×1014 vg/kg dose, with 11 sitting unassisted for ≥5 seconds, a milestone previously unachieved in the natural history of SMA type 1.

Additionally, 9 patients could roll over, 11 were fed orally and could speak, and 2 walked independently. Data also showed that at 20 months of age, all 15 patients were alive compared to a historical event-free survival rate of 8% to that point. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores increased 9.8 points from at 1 month of age and 15.4 points at 3 months, compared to historical rates of score declines.

Currently, there is a long-term follow-up trial to that study (NCT03421977) rolling over patients from the START trial, which will assess safety data over a 15-year period. Novartis reported that while all patients thus far have maintained their developmental milestones, some of the patients have achieved additional milestones.

"The introduction of one-time, potentially curative therapies will require rethinking how our healthcare system manages diagnosis, treatment, care and associated costs for patients with genetic disease,” Lennon said. “Novartis and AveXis are proud to lead the way toward a modern healthcare system built on the tremendous value of truly innovative and transformative medicines that could bend the curve of life. We are committed to flexibly partnering with healthcare stakeholders to ensure appropriate access to our medicines."

Additionally, a phase 3 trial, STR1VE (NCT03306277), of the therapy’s intravenous administration is ongoing in 15 to 20 pre-symptomatic infants with SMA types 1, 2, and 3. The open-label, single-arm, single-dose, study will assess the therapy with primary outcome measures of independent sitting and event-free survival.

AveXis is currently also assessing the treatment in an intrathecal delivery method in a phase 1 trial, STRONG (NCT03381729). This additional method would allow access to the treatment for those with SMA types 2, 3, and 4.


1. Novartis announces FDA filing acceptance and Priority Review of AVXS-101, a one-time treatment designed to address the genetic root cause of SMA Type 1 [press release]. Basel, Switzerland; Novartis; Published December 3, 2018. novartis.com/news/media-releases/novartis-announces-fda-filing-acceptance-and-priority-review-avxs-101-one-time-treatment-designed-address-genetic-root-cause-sma-type-1. Accessed December 3, 2018.

2. Mendell JR, Al-Zaidy S, Shell R. Single-dose gene-replacement therpay for spinal muscular atrophy. N Engl J Med. 2017;377(18):1713-1722. doi: 10.1056/NEJMoa1706198

Related Videos
Frederic Schaper, MD, PhD
Jaime Imitol, MD
Jason M. Davies, MD, PhD
Carolyn Bernstein, MD
Prashanth Rajarajan, MD, PhD
Mandy Alhajj, DO, James Dolbow, DO & Neel Fotedar, MD
© 2024 MJH Life Sciences

All rights reserved.