Introduction
Tenaya Therapeutics announced that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on its ongoing trial evaluating TN-201, an investigational gene therapy for MYBPC3-associated hypertrophic cardiomyopathy, a rare inherited heart disorder characterized by abnormal thickening of the heart muscle. Following the announcement, shares of Tenaya declined by more than 20% in extended trading.
Details of the Clinical Hold
The clinical hold affects the company’s early-to-mid stage phase 1b/2a study of TN-201. According to Tenaya, the FDA requested amendments to the trial protocol aimed at standardizing how participating sites monitor patients and manage immunosuppression drugs, which are used to help prevent the body from rejecting the therapy.
Reasoning Behind the Decision
Tenaya stated that the FDA’s decision was primarily based on information previously reviewed by the trial’s independent Data Safety Monitoring Board (DSMB) during the summer of 2025. The board had concluded that TN-201 had an acceptable safety profile and had authorized the expansion of patient enrollment into two dosing cohorts. “The gene therapy has been generally well tolerated so far, with no significant new safety issues since the summer review,” the company said.
The biotech attributed the clinical hold to the FDA’s request for a protocol amendment, noting that the regulatory action followed proactive discussions between Tenaya and the agency regarding next steps for TN-201. While the DSMB had permitted continued enrollment, the FDA identified the need to harmonize immunosuppression management practices across all trial locations to ensure consistency in patient care and data collection.
Company Response and Outlook
Tenaya indicated that it is working closely with the FDA to implement the requested modifications. The company expects to resume patient dosing once these updates are in place and does not anticipate that the temporary pause will alter its projected data releases or overall development timeline for TN-201.
Recent Trial Findings
Over the weekend, Tenaya presented findings from the trial at the American Heart Association’s 2025 Scientific Sessions. The company reported that adjustments to the immunosuppression schedule in the second dosing cohort led to faster tapering and reduced cumulative corticosteroid exposure, even though patients in that group received higher doses of TN-201 compared to those in the first cohort.
Early data from the second cohort showed dose-dependent increases in TN-201 transduction and MyBP-C protein expression. In the first evaluable patient of the second cohort, MyBP-C expression rose by 14% after 12 weeks, while the first cohort showed an average increase of 4% from the initial biopsy to Week 52. Additionally, cardiac troponin I levels fell between 48% and 74% in all patients from the first cohort, returning to normal or near-normal ranges. Analysts from TD Cowen had previously pointed out the normalization of troponin levels in one patient as a notable outcome when early data were released nearly a year ago.
Broader Implications and Stakeholder Impact
For patients with MYBPC3‑associated hypertrophic cardiomyopathy, these interim results present real hope for a novel treatment option targeting the underlying genetic cause. The fact that TN‑201 shows measurable improvements in biomarkers, protein expression, and cardiac structure suggests that gene therapy may become a viable approach in a condition for which options are limited.
From an industry and regulatory perspective, the hold underscores the FDA’s increasing focus on trial consistency—especially in complex gene‑therapy studies involving immunosuppression and multi‑site enrolment. The pause also sends a clear signal to investors and partners that despite promising early data, the pathway to regulatory approval will require strict protocol execution, data integrity, and patient safety.
For Tenaya itself, the share price drop reflects both the regulatory uncertainty and the stakes of advancing high‑cost gene therapies. The hold could increase operational and financial pressure, especially if additional amendments or unexpected issues arise.
