Tenaya Therapeutics Cleared to Move Onto Higher Dose Cohort in Trial of Hypertrophic Cardiomyopathy Gene Therapy TN-201
The company also announced protocol changes expanding eligibility for the MyPEAK-1 clinical trial.
Milind Desai, MD, MBA
Tenaya Therapeutics has received clearance from the independent Data and Safety Monitoring Board (DSMB) to move onto a higher dose cohort for the MyPeak-1 phase 1b clinical trial (NCT05836259) evaluating TN-201, an investigational adeno-associated virus (AAV)-vector based gene therapy intended to treat hypertrophic cardiomyopathy (HCM) caused by mutations in the MYBPC3 gene.1
The DSMB’s decision was made with reference to early safety data from 3 patients treated in the study’s first cohort, which utilized a dose of 3x1013 vg/kg of TN-201. Tenaya noted that there were no unexpected events or toxicities deemed related to the gene therapy among these patients. As such, Tenaya has received the go-ahead to dose patients in the trial’s second cohort, which will utilize a dose of 6x1013 vg/kg. The company is currently enrolling patients for this cohort.
Alongside the announcement of the DSMB’s decision, Tenaya also noted that it has made some modifications to MyPeak-1's protocol. These include the addition of a biopsy taken at baseline and greater flexibility with regard to timing for the 2 posttreatment biopsies that were already part of the protocol; the extension of eligibility to patients who have obstructive HCM and patients who do not have an implantable cardioverter defibrillator device; and raising the total possible number of participants for the dose expansion portion of the study to 24 patients. Tenaya additionally stated that it expects to report more detailed findings from the first cohort, which will include safety and tolerability data, cardiac biopsy analyses, and cardiac biomarker data, in December 2024.
“The MyPEAK-1 study of TN-201 is primarily intended to establish the safety profile of TN-201 gene therapy, and we are pleased to report that TN-201 has an appropriate tolerability profile at the 3x1013 vg/kg dose without unexpected adverse reactions,” Whit Tingley, MD, PhD, Tenaya’s chief medical officer, said in a statement.1 “The DSMB’s recommendation to proceed with dose escalation and endorsement to expand eligibility criteria are further positive early indicators for TN-201’s safety profile and enable Tenaya to explore the utility of TN-201 in different populations. We’ve implemented adjustments to the protocol, including the addition of a biopsy at baseline, broadening eligibility to include obstructive HCM patients and increasing the size of the overall MyPEAK-1 study.”
MyPEAK-1’s primary end point is safety and tolerability of TN-201, assessed via the number and severity of AEs during the study and the number of serious AEs related to the gene therapy. The secondary end point is the change from baseline to 52 weeks posttreatment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, a patient reported outcomes measure that has been associated with clinical outcomes improvement for patients with symptomatic HCM. CGTLive® has previously covered the design of the clinical trial in detail.
Following the dosing of the first patient in the trial, which Tenaya announced in October 2023, CGTLive interviewed Milind Desai, MD, MBA, an investigator on the MyPeak-1 trial, the director of the Hypertrophic Cardiomyopathy Center, and the vice chair of the Heart Vascular Thoracic Institute at the Cleveland Clinic, about the study.2 Desai emphasized the importance of rigorously evaluating safety during this early step into a very novel modality for the field of cardiology.
“At this point in time, we are just, with bated breath, looking for how this is going to evolve,” Desai told CGTLive. “This is such a new frontier in cardiovascular medicine, especially in the HCM space, that we have to ride it out. The science is there. The process has been operationalized. Now we have to wait and see the downstream ramifications of it. Based on animal data, the expectation is that this technology works, but we still have to prove it in humans.
