Tenaya’s interim MyClimb data suggest 93% of children with MYBPC3-associated HCM have the nonobstructive form with no approved therapies today, highlighting an urgent need for disease-modifying options and better risk stratification.
✨ What’s new
- The MyClimb natural history study analyzed 213 pediatric MYBPC3-HCM cases from 27 centers across the U.S., Canada, Spain, and the U.K., making it the largest study of its kind in children to date.
- Presented at ESC 2025, the interim readout shows most pediatric cases are nonobstructive, a phenotype lacking approved treatment pathways and often progressing rapidly.
🧬 Genetics that shape outcomes
- Three inheritance patterns mapped to distinct risks: homozygous (biallelic truncating variants) had the most severe, early course with transplant or death before age one in nearly all; compound heterozygous (one truncating + one missense variant) had early diagnosis and high HF hospitalization and transplant/death rates; heterozygous cases fared better but still had substantial morbidity.
- Genotype-based profiling can inform counseling, surveillance intensity, and future trial stratification to tailor emerging therapies.
📈 Biomarker signal: LVMI
- Left Ventricular Mass Index emerged as a predictor of adverse events: each 10 g/m² increase was associated with about a 10% higher hazard of serious outcomes in compound heterozygous and heterozygous groups.
- Investigators propose LVMI as a practical surrogate endpoint to gauge early efficacy in pediatric gene therapy trials targeting MYBPC3.
🧒 Clinical gap in pediatrics
- With 93% nonobstructive HCM and no approved therapies, current pediatric management leans on invasive interventions (ICDs, transplant) that do not address root causes and carry complication risks—underscoring unmet need.
- The study reinforces the importance of genetic diagnosis, family counseling, and close monitoring to anticipate arrhythmias, HF hospitalizations, and transplant needs.
🧪 Pipeline context: TN‑201 gene therapy
- Tenaya’s AAV9 gene therapy TN‑201 delivers a functional MYBPC3 via single IV infusion; early-phase data showed initial patients improving to NYHA Class I, with more cohort data expected in Q4 2025.
- Regulatory momentum includes U.S. Fast Track, Orphan Drug, Rare Pediatric Disease designations and EU orphan designation, enabling accelerated development if efficacy signals persist.
❓ FAQ
- What makes pediatric MYBPC3-HCM different?
Earlier onset, faster progression, and higher risk tied to genotype compared with many adult cases, necessitating pediatric-specific data and endpoints. - Why is nonobstructive HCM so challenging?
Lack of obstruction-focused drug targets leaves few options; disease-modifying strategies must address sarcomeric deficiency and remodeling. - How could LVMI help trials?
As a quantifiable, prognostic marker, LVMI can shorten study timelines by reflecting early structural change before hard outcomes accrue. - Is gene therapy realistic for kids?
Early signals are encouraging; durability, dosing, and safety will drive viability, with regulatory designations supporting pathway acceleration.
