AveXis is postponing plans to open a clinical trial of its Rett syndrome gene therapy candidate AVXS-201. “Out of caution,” it will instead conduct additional preclinical tests and quality controls checks before asking for new regulatory approval for a study in patients.
In a statement to the Rett syndrome community, the Novartis-owned company said this decision was based on concerns with animal data given to the the U.S. Food and Drug Administration (FDA) to support its approval of Zolgensma (onasemnogene abeparvovec-xioi) for children with spinal muscular atrophy (SMA) up to age 2.
These concerns are of “data manipulation issues” that led to inaccuracies in AveXis’ FDA application for that gene therapy, and center on early tests using older and newer versions of Zolgensma. In response, AveXis chose to review data quality and compliance in its preclinical work with AVXS-201.
“Out of caution, and to ensure that we have a robust data package for the FDA we have chosen to repeat and add additional pivotal preclinical studies as well as new quality controls,” the company announced.
AveXis expects to complete the new studies and submit a revised investigational new drug application to the FDA, a necessary step in starting a clinical trial, in mid-2020. At that time, it will again update the Rett syndrome community.
“We recognize that this news will cause concern and disappointment,” the company said. It also reaffirmed its commitment “to the Rett program and to ensuring the highest levels of transparency and integrity with the patients and providers we serve, and health agencies.”
“Rett Syndrome continues to be a key focus for AveXis and we maintain a high sense of urgency to progress clinical studies for AVXS-201,” said Dave Lennon, the company’s president.
“We look forward to serving as a trusted member of the Rett Syndrome community and partnering with patients, advocates, physicians and regulators as we work to better understand the clinical impact of gene therapy,” he added.
A new start date for an AVXS-201 clinical trial will depend on FDA acceptance of the revised application.
According to a USA Today report written by Ken Alltucker, AveXis learned of problems with its preclinical data for Zolgensma on March 14, but only informed the FDA on June 28, well after the therapy’s May 24 approval. AveXis has said that the agency was notified of the manipulation once it and Novartis had “interim conclusions from our investigations.”
The FDA considers the matter very serious and warned that AveXis could face civil or criminal penalties, officials said in an Aug. 6 statement. But, they added, Zolgensma’s safety and effectiveness are not in question as the problematic data are only a “small portion” of the “large amount of submitted information.”
AveXis also announced that Page Bouchard was named the company’s senior vice president of research and chief scientific officer on Aug. 5. Bouchard is leading the management team responsible for the Rett program. He has worked in the pharmaceutical industry for 27 years, including a position as global head of preclinical safety for Novartis Institutes for BioMedical Research.
Bouchard replaces Brian Kaspar as CSO and Allan Kaspar as senior VP for research and development, AveXis announced, adding that both men have not “been involved in any operations at AveXis since early May 2019 and are no longer with the company.”