After FDA Lifts Hold, Novartis to Proceed with Clinical Trials for Expensive Rare Disease Therapy

Novartis’ Zolgensma (OAV-101) is a one-time gene therapy that uses an adeno-associated viral (AAV) vector to deliver a copy of the functional SMN gene to treat spinal muscular atrophy (SMA). To date, Zolgensma is approved in 41 countries, and more than 1,400 patients have been treated. With a price tag of more than $2 million, it is the most expensive gene therapy in the market. In 2020, Zolgensma raked in almost $1 billion in sales for Novartis.

In 2019, Zolgensma became the first FDA-approved gene therapy to treat children younger than 2 years old suffering from SMA. Soon after, it became embroiled in a scandal after reports of data manipulation involving top executives of AveXis, the company that initially developed the drug, emerged.

Later that year, Novartis suffered another major setback after the FDA imposed a partial clinical hold for trials for OAV-101 delivered into the spinal canal. However, that did not affect the marketing of Zolgensma or trials using an intravenous injection. The hold was imposed after an animal study showed inflammation of the dorsal root ganglia (DRG) mononuclear cell, resulting in neuronal damage.

FDA Lifts Clinical Hold

After almost 2 years, on August 3rd, Novartis announced that the FDA had lifted the partial hold following a comprehensive study conducted in non-human primates, which addressed the questions regarding the injury to dorsal root ganglia.

After consulting with the FDA and European Medicines Agency (EMA), Novartis is now moving forward with STEER, a global, randomized, double-blind, sham-controlled Phase 3 study to evaluate the safety, efficacy, and tolerability of OAV-101 delivered into the spinal canal. The trial will enroll treatment naïve patients with Type 2 SMA between the ages of 2 and 18 years of age who are able to sit but never walked. Significant unmet needs remain for these patients who suffer from a later-onset SMA.

“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,” said Shephard Mpofu, M.D., SVP, Chief Medical Officer, Novartis Gene Therapies.

“We believe that all patients diagnosed with SMA should be able to benefit from the transformative impact of gene therapy, and we remain confident that investigational OAV-101 IT is a viable potential treatment path for older patients who often have ongoing unmet needs, and for whom a one-time treatment could be especially compelling.”

This study will complement topline results from two Phase 3 clinical trials showing the efficacy of Zolgensma in patients younger than 6 weeks of age and pediatric patients presenting symptoms prior to treatment.

This news provides further validation for AAV-based genetic therapies, including therapies for Rett syndrome and Friedreich’s ataxia that are part of the Novartis pipeline.

Author

Daniel Ojeda

Related Post

Prime

Chinese Bispecific Antibody Tops Keytruda in First Head-to-Head OS Win; SMA Muscle-Strengthening Therapy Approved, B7-H3 ADC Shows Promise

2026-09-14

Prime

Breaking Genetic Shackles: In Vivo Gene Editing Technologies Broaden the Path to Rebirth for Rare Diseases

2026-09-10

Prime

The Trojan Horse Penetrating Cellular Walls: How “The Delivery of Gene Therapy” Overcomes Capacity and Immunological Barriers

2026-09-10