FDA Puts Clinical Hold on Tenaya Therapeutics' Heart Disease Gene Therapy Trial

The U.S. Food and Drug Administration (FDA) has placed a clinical hold on Tenaya Therapeutics' gene therapy study for MYBPC3-associated hypertrophic cardiomyopathy. The hold comes as the biotech company works to standardize immunosuppression regimens across trial sites for its TN-201 therapy.

Clinical Trial Protocol Amendment Required

Tenaya Therapeutics reported that the FDA has requested changes to the protocol for the phase 1b/2a trial of TN-201. This decision follows proactive correspondence between the company and the regulatory agency regarding the next steps for the gene therapy candidate. The primary basis for the hold stems from data reviewed by the trial's data safety monitoring board (DSMB) earlier this year.

While the DSMB had previously approved enrollment in expansion cohorts at two doses in July, the FDA has now identified the need to standardize patient monitoring and management activities related to immunosuppression across all trial sites. Tenaya attributes the clinical hold directly to the FDA's request for a protocol amendment.

Safety Profile and Development Timeline

Despite the setback, Tenaya maintains that TN-201 has been generally well-tolerated thus far. The company stated that no new significant safety events associated with the gene therapy have emerged since the DSMB's review. Tenaya plans to resume dosing once the required protocol changes have been implemented at all trial sites and does not anticipate that the FDA hold will impact data milestones or overall development timelines for TN-201.

Early Clinical Data Shows Promise

At the American Heart Association's 2025 Scientific Sessions, Tenaya presented data from the ongoing phase 1b/2a trial. The results revealed that shortening the course of immunosuppression in the second cohort led to faster tapers and lower cumulative corticosteroid doses, despite patients receiving higher doses of TN-201 compared to the first cohort.

Initial results from the second cohort demonstrated early dose-responsive increases in TN-201 transduction and MyBP-C protein expression. After 12 weeks, MyBP-C expression increased by 14% in the first evaluable patient of the second cohort. This compares favorably to the average 4% increase observed from the first biopsy to Week 52 in the first cohort.

Furthermore, cardiac troponin I levels, a key biomarker, declined by 48% to 74% to normal or near-normal levels in all patients in the first cohort. TD Cowen analysts have previously highlighted the normalization of troponin levels as a particularly encouraging sign for the therapy's potential efficacy.

As Tenaya Therapeutics works to address the FDA's concerns and standardize its trial protocols, the pharmaceutical industry will be closely watching for further developments in this promising gene therapy approach to treating hypertrophic cardiomyopathy.