The FDA is putting Atara’s active Investigational New Drug applications on hold due to manufacturing concerns at a third-party provider while releasing Amylyx’s investigational ALS therapy from a previous pause.
The FDA has slapped a clinical hold on Atara Biotherapeutics’ active drug applications due to unresolved manufacturing concerns, the California biotech announced on Tuesday.
The regulatory pause will affect Atara’s Investigational New Drug application for Ebvallo (tabelecleucel), a T cell therapy being developed for patients with post-transplant lymphoproliferative disease who are positive for the Epstein-Barr virus. The company’s allogeneic CD19 CAR T therapy ATA3219, being tested for non-Hodgkin’s lymphoma and systemic lupus erythematosus, is also subject to the clinical hold.
Under the hold, screening and enrollment of new study patients in both programs are suspended. Only patients already currently enrolled in the trials, and who have been identified to “potentially derive clinical benefit,” can continue receiving the treatments under study protocols.
According to Atara, the freeze on Ebvallo is related to “inadequately addressed” compliance problems with Good Manufacturing Practices at a third-party manufacturing site. ATA3219 is produced at a different—and fully compliant—facility, but certain starting materials involved in its synthesis are made in the facility with compliance violations.
Atara and the FDA have agreed on the requirements to release the clinical holds, and the biotech plans to “address these issues as expeditiously as possible,” CEO Cokey Nguyen said in a statement.
Tuesday’s clinical hold comes nearly a week after the FDA rejected Ebvallo, citing the same manufacturing concerns that led to the clinical hold. At the time, however, Atara insisted that the rejection was not linked to safety concerns with the drug. Ebvallo is approved for use in the European Union and in the U.K.
Also on Tuesday, the FDA released its hold on Amylyx Pharmaceuticals’ investigational antisense oligonucleotide (ASO) AMX0114, which the biotech is advancing for amyotrophic lateral sclerosis (ALS). With the pause lifted, Amylyx can now continue opening U.S. sites for screening, enrollment and dosing for its Phase I study.
Amylyx is also gearing up to launch a multiple ascending dose Phase I trial of AMX0114, dubbed LUMINA, in Canada, to assess the safety and biological activity of the ASO candidate, as well as its impacts on key ALS biomarkers such as neurofilament light concentration. LUMINA is set to start “in the beginning of 2025,” the company said in an announcement, and is expected to readout early cohort data this year.
Amylyx first announced AMX0114’s clinical hold in its third-quarter business report in November 2024. At the time, the biotech announced that the FDA has “restricted dosing to an amount that is lower than the Company’s proposed starting dose of 12.5 mg.” The regulator also asked for additional information regarding the candidate, resulting in the regulatory pause.
Amylyx is trying to resurrect its ALS portfolio after it was forced to withdraw Relyvrio (sodium phenylbutyrate and taurursodiol) from the U.S. and Canadian markets after it failed its Phase III confirmatory trial. Relyvrio was originally approved in September 2022 under the FDA’s accelerated pathway.
