Trametinib, a MEK inhibitor, significantly reduces mortality, heart transplants, and the need for cardiac surgery in children with RASopathy-associated hypertrophic cardiomyopathy (RAS-HCM), according to a study. Compared to standard therapies alone, trametinib-treated patients demonstrated a substantial reduction in adverse outcomes (17% vs. 87%, HR: 0.09, 95% CI: 0.04-0.25, p < 0.001).

The retrospective study, published in JACC: Basic to Translational Science, analyzed 61 children from 23 international centers, with 30 receiving trametinib and 31 managed on standard care. The drug also improved key cardiac markers, including myocardial wall thickness z-scores (−1.4 vs. −0.3 in controls, p = 0.009), and reduced NT-proBNP levels, a biomarker for heart failure.

Trametinib was well-tolerated overall, with mild to moderate side effects such as dermatologic and mucosal issues, effectively managed with dose adjustments. No life-threatening events were reported, reinforcing its safety profile for pediatric use.

RASopathies, including Noonan syndrome, stem from mutations in the RAS/MAPK pathway, leading to abnormal cell signaling and developmental complications. Approximately 20% of children with RASopathies develop HCM, a leading cause of morbidity and mortality. Conventional treatments have limited success, emphasizing the potential of trametinib as a game-changer.

The authors stated: “Our retrospective study corroborates the beneficial effects of MEKi observed in preclinical models as well as in previously reported anecdotal clinical applications with data from more patients with other genetic etiologies, longer follow-up, and detailed covariate analysis.”

While the findings are promising, the study’s retrospective design and small cohort size underscore the need for larger, prospective trials to confirm these outcomes.

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