RARE Daily

Novartis Will Conduct Additional Zolgensma Trial for Older Patients

September 23, 2020

Rare Daily Staff

Novartis Gene Therapies said it would initiate a new pivotal confirmatory study evaluating the use of SMA gene therapy in older patients with SMA to further support registration based on feedback from the U.S. Food and Drug Administration on its STRONG study.

The FDA recommended a pivotal confirmatory study to supplement the existing STRONG data and further support the regulatory submission for Zolgensma (AVXS-101). The STRONG study involved intrathecal formulation of AVXS-101 in older patients with spinal muscular atrophy (SMA).

The company said the request for a study is unrelated to the partial clinical hold on AVXS-101 IT, and the new study will not be initiated in the United States until the hold has been lifted by the FDA. In October 2019 the FDA placed a partial clinical hold on Zolgensma intrathecal clinical studies based on findings from a small pre-clinical animal study, which found inflammation to a group of cells involved in the transmission of sensory messages.

The trial design and other details of the new study are being evaluated and Novartis said it will provide a comprehensive update on the overall Novartis SMA clinical development program following further discussions with health authorities. It does not affect the marketing of Zolgensma.

SMA is a rare, genetic neuromuscular disease caused by a lack of a functional SMN1 gene, resulting in the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement. Loss of motor neurons cannot be reversed, so SMA patients with symptoms at the time of treatment will likely require some supportive respiratory, nutritional and/or musculoskeletal care to maximize functional abilities. More than 30 percent of patients with SMA Type 2 will die by age 25.

Zolgensma is designed to address the genetic root cause of SMA by providing a functional copy of the human SMN gene to halt disease progression through sustained SMN protein expression with a single, one-time IV infusion. The FDA approved Zolgensma in May 2019.

The therapy is approved in the United States, Japan and, most recently, Brazil, for patients with SMA under the age of two. Zolgensma also continues to have a strong launch in Europe where it is approved for babies and young children with a clinical diagnosis of SMA Type 1 or SMA with up to three copies of the SMN2 gene, with dosing guidance provided up to 21 kg.

SMA is the leading genetic cause of infant death. If left untreated, SMA Type 1 leads to death or the need for permanent ventilation by the age of two in more than 90 percent of cases.


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