Novartis has announced the US Food and Drug Administration has lifted its partial clinical trial hold on the company’s intrathecal (IT) formulation of onasemnogene abeparvovec (Zolgensma®), called OAV-101 IT, which is being developed for use in people with spinal muscular atrophy (SMA).

Clinical trials for OAV-101 IT were placed on hold in October 2019 due to results in nonclinical experiments that indicated the potential for injury to the dorsal root ganglia (DRG) after IT administration. The FDA decided to lift the ban after extensive nonclinical toxicology testing in primates.

With the hold lifted and feedback from the FDA and European Medicines Agency (EMA), Novartis has decided to initiate a global phase 3 trial, called STEER, to further investigate OAV-101 IT in people with SMA. The trial will recruit patients with SMA between the ages of 2 to 18 years who can sit but have never been able to walk.

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Shephard Mpofu, MD, senior vice president and chief medical officer at Novartis Gene Therapies, stated, “we are very pleased that our comprehensive nonclinical data package has addressed all issues identified related to DRG toxicity and the FDA has reached the decision that we may proceed with our OAV-101 IT clinical trial program and initiate the STEER trial.”

OAV-101 IT was previously investigated in a phase 1/2 clinical trial called STRONG (NCT03381729). That trial showed significant improvements in Hammersmith Functional Motor Scale-Expanded (HFMSE) scores in SMA type 2 patients between the ages of 2 and 5 years before being halted by the clinical hold.

The STEER trial will recruit more than 100 SMA type 2 patients between 2 and 18 years of age to receive either a single IT administration of OAV-101 or a sham control before being monitored for a 52-week period. At the end of the 52 weeks, patients in the control group will be given OAV-101 while patients who initially received treatment will receive the sham procedure. Patients will be monitored for changes primarily in HFMSE score but also in the Revised Upper Limb Module (RULM) scale and safety endpoints.

Kenneth Hobby, president of Cure SMA, stated, “this route of administration has the potential to open up access for older patients to all the benefits of gene therapy.”


Novartis announces lift of partial clinical trial hold and plans to initiate a new, pivotal phase 3 study of intrathecal OAV-101 in older patients with SMA. News release. Novartis; August 3, 2021. 

Study of intrathecal administration of onasemnogene abeparvovec-xioi for spinal muscular atrophy. US National Library of Medicine. Accessed August 4, 2021.