Tenaya Therapeutics Receives Positive Safety Reviews for TN-201 and TN-401 Gene Therapy Trials

Analysis reveals significant industry trends and economic implications

Release Date

2025-07-31

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Tenaya Therapeutics announced positive safety reviews from independent Data Safety and Monitoring Boards (DSMBs) for its two cardiovascular gene therapy clinical trials: MyPEAK-1 (TN-201 for hypertrophic cardiomyopathy) and RIDGE-1 (TN-401 for arrhythmogenic right ventricular cardiomyopathy). Both trials are progressing as planned, with enrollment complete for MyPEAK-1's first two cohorts and the first patient dosed in the second cohort of RIDGE-1. The DSMBs' endorsements allow for expansion cohorts at different dose levels for both TN-201 and TN-401. Tenaya plans to release clinical data from both trials in the fourth quarter of 2025, focusing on safety, tolerability, and efficacy.

Key Highlights

  • Positive DSMB reviews for both MyPEAK-1 (TN-201) and RIDGE-1 (TN-401) trials allow for continued progression.
  • Enrollment complete for MyPEAK-1's Phase 1b/2 trial, with follow-up data expected in Q4 2025.
  • First patient dosed in RIDGE-1's second cohort, with initial data expected in Q4 2025.
  • Data will inform dose selection and pivotal study design for both TN-201 and TN-401.

Incidence and Prevalence

Latest Estimates of Hypertrophic Cardiomyopathy Incidence and Prevalence

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease according to the most recent data from 2018. The global epidemiology of HCM shows significant variations in reported figures and regional differences.

Prevalence

Reported prevalence rates for HCM vary substantially between 1:500 (0.2%) and 1:3,000 (0.03%), with variations likely attributable to different study designs and population characteristics.

In Germany, a 2018 study analyzing health care claims data of over 5 million insurants found the prevalence of clinically diagnosed HCM was 0.07% (or 1:1,372). This is lower than in systematic population studies based on echocardiographic diagnosis.

The German data showed a gradual annual prevalence increase from 75.8 per 100,000 persons in 2011 to 84.2 per 100,000 persons in 2015.

Age and Gender Distribution

HCM prevalence demonstrates clear demographic patterns:

  • HCM prevalence increased gradually with age from 7.4/100,000 persons in 0-9 years old to 298.7/100,000 persons in patients over 80 years.
  • In all age categories, men had a numerically higher prevalence than women with significant differences in patients over 30 years.

Incidence

A 2021 Korean nationwide population-based study found an incidence rate of clinical HCM of 0.059 per 1000 person-years, with 0.027% of study participants diagnosed with incident HCM over a median follow-up of 5.2 years.

Regional Variations

Apical hypertrophic myocardiopathy (AHM) is reported to be less frequent in some countries compared to Japan. Apical HCM is a specific variant that is common in Japanese and other Asian populations but is rare in the United States.

Mortality Rates

Natural history studies reported total HCM-related mortality rates varying by age: - 1.8% per year for ages 5-15 years - 1.0% to 1.5% for ages 16-65 - 3.9% for ages 66-75 - 4.7% for ages above 75 years

Sudden death rates varied from 0.5% to 1.5% per year for most age groups, with children and adolescents experiencing rates near the top of this range.

A 2001 regional cohort study of 243 HCM patients found an average age at diagnosis of 40.4 years with an annual cardiac mortality rate of 1.37%.

Risk Factors

Obesity and metabolic health status are associated with the incidence of clinical HCM diagnosis, with a hazard ratio of 1.063 per 1 kg/m² increase in BMI after multivariate adjustment. The effect of BMI was more pronounced in several subgroups, including participants with no hypertension, those aged less than 65 years, and men.

Metabolically unhealthy participants had a greater incidence of HCM than metabolically healthy participants, regardless of obesity status.

Genetic Factors

A 2021 study identified 16 loci associated with HCM through genome-wide association studies. HCM is an inheritable cause identified in approximately half of patients according to a 2022 study that included 422 HCM patients (46% genotype-negative, 54% genotype-positive).

Study Design Parameters

Summarizing Study Design Parameters and Endpoints in Key Hypertrophic Cardiomyopathy Trials

Study Designs

  • Genetic testing studies utilized array-based resequencing (ABR) covering the 3 most commonly affected genes: MYH7, MYBPC3, and TNNT2
  • A Brazilian tertiary centre cohort study evaluated clinical predictors using echocardiographic, electrocardiographic, and nuclear magnetic resonance measures
  • A single-centre, randomized, double-blind, placebo-controlled trial assessed losartan (100 mg daily) versus placebo for 12 months in HCM patients
  • The ENERGY Trial (2013) was a double-blind randomized study of 40 genotype-positive, phenotype-negative MYH7 mutation carriers receiving trimetazidine or placebo
  • The ALLAY Trial (2012) randomized 465 patients with LVH to aliskiren 300mg, losartan 100mg, or both for 36 weeks
  • The REHAB-HCM Study (2025) is a prospective observation cohort study with a 3-month cardiac rehabilitation program for HCM patients with metabolic syndrome
  • A retrospective analysis of 1,940 consecutive HCM patients identified 93 patients with LV apical aneurysms
  • A study of 31 adult HCM patients with HFpEF who underwent Percutaneous Intramyocardial Septal Radiofrequency Ablation (PIMSRA)
  • A retrospective analysis of 462 patients with apical hypertrophic cardiomyopathy (aHCM)
  • A descriptive study of 34 patients with obstructive HCM for whom mavacamten was considered

Primary Endpoints

  • Genetic testing studies: Detection of underlying point mutations and variants
  • Losartan trial: Change in left ventricular mass assessed by cardiac magnetic resonance imaging
  • ENERGY Trial: Myocardial efficiency calculated as oxygen consumption for heart work
  • ALLAY Trial: LVH regression assessed by cardiac magnetic resonance imaging
  • REHAB-HCM Study: Feasibility, safety, and efficacy of cardiac rehabilitation
  • LV apical aneurysm study: Sudden death, appropriate implantable cardioverter-defibrillator discharges, or need for cardiac transplantation
  • PIMSRA study: Changes in left ventricular diastolic function and clinical symptoms improvement
  • aHCM study: Death, appropriate defibrillator discharge, or need for cardiac transplantation
  • Mavacamten study: Implementation of clinic workflow, including cost reduction measures and monitoring requirements

Secondary Measurements

  • Left ventricular outflow tract pressure gradients (resting and postexercise)
  • Interventricular septal thickness
  • E/e ratio for diastolic function
  • 6-minute walk distance (6MWD)
  • Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ OS)
  • Left ventricular ejection fraction
  • Left atrial volume index
  • Right ventricular systolic pressure
  • Delayed gadolinium enhancement on cardiac magnetic resonance
  • Fractal dimensions (FDs) and myocardial strain parameters
  • N-terminal pro-B-type natriuretic peptide
  • Maximum wall thickness
  • Coronary blood flow and coronary flow reserve
  • Time constant of isovolumic LV pressure relaxation (tauG)

Key Findings

  • Losartan trial: No significant difference in left ventricular mass between placebo and losartan groups
  • LV apical aneurysm study: Sudden death event rate of 4.7%/year
  • PIMSRA study: Significant reductions in pressure gradients and improvements in quality of life
  • aHCM study: Composite event rate of 2.8%/year
  • Mavacamten study: High patient adherence (99.1%) with improvements in left ventricular outflow tract parameters
  • 2024 network meta-analysis: Mavacamten improved peak oxygen consumption, reduced N-terminal pro-B-type natriuretic peptide, left ventricular mass index, and left atrial volume index

Drug used in other indications

TN-201 Clinical Trials Beyond Hypertrophic Cardiomyopathy

Based on a comprehensive review of available information, there is insufficient data to determine what other indications TN-201 is being trialed for beyond hypertrophic cardiomyopathy. The clinical trial landscape for this specific gene therapy appears to be limited or not publicly documented in the sources examined.

Without confirmed information about additional indications, it is not possible to describe the intervention models, dosing regimens, or administration protocols being utilized in trials for non-hypertrophic cardiomyopathy indications.

Hypertrophic cardiomyopathy (HCM) remains the primary focus of TN-201 development based on available information. HCM is characterized by abnormal thickening of the heart muscle, particularly affecting the left ventricle, which can lead to outflow obstruction and various cardiac complications.

For patients interested in TN-201 clinical trials, it would be advisable to consult official clinical trial registries such as ClinicalTrials.gov or contact the developing company directly for the most current information on ongoing or planned studies across different indications.

The field of cardiac gene therapy continues to evolve, with various therapeutic candidates being investigated for different cardiovascular conditions. As research progresses, additional indications for TN-201 may emerge in the future.