Differences and potential advantages of aficamten compared to BMS’s Camzyos

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The recent analysis from Cytokinetics has highlighted several key differences and potential advantages of aficamten compared to Bristol Myers Squibb's Camzyos, both of which are cardiac myosin inhibitors used in the treatment of obstructive hypertrophic cardiomyopathy (HCM).

Key Differences

  1. Pharmacodynamic Profile: Aficamten, being a next-generation myosin inhibitor, has a different pharmacodynamic profile compared to mavacamten (Camzyos). It is designed to decrease the number of myosin head and actin filament interactions, which reduces the force of contractility and lowers outflow tract gradients 5. This difference in the pharmacologic profile could potentially translate into differences in efficacy and safety, although more data is needed to confirm this 5.
  2. Half-Life and Dose Response: Aficamten has a shorter half-life compared to mavacamten, which allows for more rapid dose titrations and drug washout, providing a wider therapeutic window 15. This could be particularly advantageous in managing the dosing and withdrawal in response to any adverse effects.

Potential Advantages

  1. Improvement in Exercise Capacity and Symptoms: In the SEQUOIA-HCM trial, aficamten showed significant improvements in exercise capacity and symptoms of obstructive HCM. It was reported to improve peak oxygen uptake significantly compared to placebo, with a least square mean difference of 1.74 mL/kg/min 7 10. Additionally, aficamten achieved statistically significant improvement in all 10 prespecified secondary endpoints 10.
  2. Safety Profile: Aficamten was well tolerated with an adverse event profile comparable to placebo. Importantly, there were no instances of worsening heart failure or treatment interruptions due to low left ventricular ejection fraction (LVEF) 10. This contrasts with Camzyos, where some patients experienced reductions in LVEF that required treatment interruption 11.
  3. Direct Comparison in Clinical Trials: Direct comparison data from the SEQUOIA-HCM trial suggests that aficamten might have a more favorable placebo-adjusted difference in exercise capacity and symptom improvement compared to Camzyos. In the aficamten trial, 42% of people met the composite exercise capacity and symptom endpoint, compared to 14% on placebo. This is a larger placebo-adjusted difference than in the Camzyos trial, where 37% of patients on the drug met the response criteria versus 17% on placebo 4.
  4. Potential for Less Restrictive Monitoring: Given the safety profile observed in clinical trials, aficamten might be managed with a less restrictive Risk Evaluation and Mitigation Strategy (REMS) program compared to Camzyos, which requires frequent monitoring due to the risk of heart failure from systolic dysfunction 11 9.

In summary, aficamten appears to offer several potential advantages over Camzyos, including a possibly better safety profile, greater improvements in exercise capacity and symptoms, and less restrictive monitoring requirements. However, ongoing and future studies will be crucial to fully establish these benefits and to answer remaining questions about the comparative efficacy and safety of these two treatments for obstructive HCM 4 5 10.

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