Cytokinetics prepares to take on BMS’ Camzyos in HCM
Cytokinetics has revealed the results from a phase 3 trial of its hypertrophic cardiomyopathy (HCM) drug aficamten that it hopes will allow it to compete with Bristol-Myers Squibb’s first-to-market Camzyos.
The full data from the SEQUOIA-HCM study have been presented at the European Society of Cardiology (ESC) conference and simultaneously published in the New England Journal of Medicine, showing that the drug raised peak oxygen uptake (pVO2) significantly better than placebo in patients with obstructive HCM.
Cardiac myosin inhibitor aficamten improved pVO2 by 1.74 ml/kg/minute compared to placebo as measured by cardiopulmonary exercise testing (CPET) after 24 weeks. That is slightly better than was achieved by Camzyos (mavacamten) in its phase 3 programme, with the usual caveat about trying to compare studies with different protocols, and it is worth noting that any increase above around 1 ml/kg/minute is considered clinically meaningful.
Cytokinetics’ drug also showed a significant benefit on 10 secondary endpoints, including exercise capacity, symptoms, cardiac function and cardiac biomarkers.
SEQUOIA-HCM lead investigator Martin Maron of Lahey Hospital and Medical Centre in the US told the congress that one of the key features of aficamten is the consistency of its effects across endpoints in the study, including in patients also taking beta blockers, as well as its relatively short half-life.
The short half-life means patients can be titrated to an optimal dose to get the benefit of the drug more quickly, whilst reducing the risk of side effects like a drop in ejection fraction – how much blood the left ventricle of the heart can pump out with each contraction – which is a consequence of cardiac myosin inhibition.
Maron also said that aficamten has a wider therapeutic window, with each increase in dose with aficamten accompanied by a smaller reduction in ejection fraction than with BMS’ drug, while the short half-life also means treatment can be reversed quickly if patients have adverse events.
Camzyos is currently the only FDA-approved treatment for HCM and at launch was tipped as a future blockbuster, although its growth has been pegged back by a somewhat onerous risk evaluation and mitigation strategy (REMS) that has limited take-up of the drug.
First approved in April 2022, Camzyos made $231 million in sales in 2023 but showed signs of a slowdown in the first quarter of this year and didn’t meet analyst expectations.
Cytokinetics’ head of R&D, Fady Malik, said that the SEQUOIA-HCM data revealed that aficamten provides “rapid and sustained” improvement in exercise capacity, symptoms, cardiac function and cardiac biomarkers coupled and was well-tolerated, with no treatment interruptions due to low ejection fraction.
“We believe these results are strongly supportive of the potential approval of aficamten, and we look forward to submitting regulatory filings in both the US and Europe later this year,” he added.
In its first-quarter results call last week, Cytokinetics said it expected to file the drug with the FDA in the third quarter and EMA in the fourth quarter and is in the process of building its commercial operations in anticipation of a launch in 2025.
Chief executive Robert Blum said the near-term objective isn’t to switch patients from Camzyos but to expand the market with aficamten, given that the vast majority of obstructive HCM patients are not being treated with BMS’ drug and relying on older therapies like beta blockers.
He also said he did not anticipate that the FDA will require an advisory committee meeting for the drug, or give it a priority review, given that Camzyos is already available.
Photo by Casey Horner on Unsplash
