Tag: mavacamten

Will Cytokinetics New HCM Drug Challenge Camzyos?

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Cytokinetics, a San Francisco biotech company, is hoping that its experimental HCM drug, aficamten, will soon be a competitor to Bristol Myers Squibb’s first-in-class myosin inhibitor Camzyos (mavacamten). Aficamten is an oral cardiac myosin inhibitor which, like Camzyos, treats HCM by reducing the the excessive number of interactions between cardiac myosin proteins.

An earlier Phase 2 study called Redwood-HCM established the safety of the drug.  The positive results of Redwood-HCM led to the Phase 3 study entitled Sequoia – HCM.

Topline results of Sequoia-HCM were presented in late December of 2023, while primary results and data from the study were presented on May 13 at tthe European Society of Cardiology Heart Congress meeting held in Lisbon, Portugal.  The complete paper was published in the New England Journal of Medicine on May 13, 2024.

The Study:  The study enrolled 282 patients with obstructive HCM.  Half were assigned to the drug while half took a placebo drug instead.  The total period of observation for the study was 28 weeks.  Patients enrolled in the study took aficamten for 24 weeks, followed by a 4 week period for washout of the drug.  Patients in both groups were allowed to stay on background therapies including beta blockers, calcium channel blockers, and disopyramide.

Primary Endpoint:   The primary endpoint of the study, as well as all 10 secondary endpoints, were met with statistically meaningful results.  The primary endpoint showed an improvement to exercise capacity, quantified by an increase in peak oxygen uptake (pVO2) as measured by cardiopulmonary exercise testing (CPET) on a treadmill or bike by 1.8 ml/kg/min over a period of 24 weeks.

The study results also met multiple secondary endpoints including:

Subjective Improvement in Symptoms:  Patients scores showed a 7 point increase on the Kansas City Cardiomyopathy Questionnaire.  This is a questionnaire that has been validated for measuring heart failure symptoms over time by asking individuals repeated questions about how they are feeling.

Improvement in functional capacity:  34% of patients experiencing ≥1 class improvement as measured by New York Heart Association (NYHA) class (which is determined by the medical team after observation and questioning).

Septal Reduction Therapy Eligibility:  Almost all of the patients who qualified for septal reduction therapy at the start of the study no longer qualified for invasive septal reduction therapies at the end (i.e. septal myectomy and septal alcohol ablation).

Safety:  Aficamten was found to be safe and well tolerated.  There was no need to interrupt treatment for heart failure when a patient’s ejection fraction fell below 50%.  If a patient’s ejection fraction (EF) did fall below 50%, the EF recovered either spontaneously or when the aficamten dosage was decreased.

No differences in response were seen in responders based on age, sex or usage of background drug therapies.

When will Aficamten be available to patients? 

Cytokinetics expects to file for regulatory approval in both the U.S. and Europe by the end of the 2024.  They hope that they will be able to bring the drug to market by the end of 2025, depending on the timing and results of the regulatory process.  The prescribing information and any restrictions surrounding use (i.e. the necessity and frequency of repeat echocardiograms and REMS program, both which are mandated for Camzyos) will also be determined by regulators.

For more about aficamten see these past blogs on HCMBeat:

Is Aficamten the Blockbuster Drug Cytokinetics is Hoping For?

Cytokinetics Teases Upcoming Phase 3 Aficamten Trial in nHCM

Promising Data about Aficamten Presented at Meetings

Aficamten Updates from Cytokinetics

More on Aficamten & Mavacamten from ACC 2022

Aficamten Gets “Breakthrough Drug” Status from FDA

Cytokinetic’s Drug Aficamten & Upcoming HCM Summit – Interview with Dr. Martin Maron

2024 Updated Guidelines for Management and Treatment of HCM

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The American Heart Association/American College of Cardiology (AHA/ACC) Guidelines for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy published in 2020 have been updated for 2024 to address certain new developments in the field including the addition of myosin inhibitor such as Camzyos (mavacamten) to the treatment arsenal, as well as the benefits of exercise for the HCM population.

The 2024 guidelines update the most recent version published in 2020.  In the past,  guidelines were only updated every decade or so, but with the recognition of major changes in the treatment of HCM with the addition of new drugs such as mavacamten, AHA/ACC wants to keep the guidelines current with emerging developments.  Guidelines are compiled following review and discussion by a committee of HCM experts with reference to the latest published HCM literature.  The document addresses the broad spectrum of issues seen by medical professionals who are called upon to diagnose and treat patients and families affected by hypertrophic cardiomyopathy.

Two patients served on the writing committee for this 2024 update:  Cynthia Burstein Waldman, a HCM patient who is the Founder and Editor of the blog HCMBeat was privileged to sit on the writing committee alongside congenital heart patient and 2020 guidelines committee member Lauren Evanovich and the esteemed panel of medical professionals. Together the committee members discussed the latest research and determined best practices for addressing all facets of HCM.  The inclusion of patients on the committee provides a real world perspective focusing the discussion through the lens and experience of people who have actually lived through and dealt with these and similar medical issues. Lauren and I hope and believe that our input was useful and we are grateful to have played a small part in moving things forward for HCM patients.

Some key updates to the 2024 guidelines include:

  • New Drug Options:  Cardiac myosin inhibitors such as Bristol Myers Squibb’s mavacamten (Camzyos) are now an option to treat patients with obstructive HCM who do not see improvement to their symptoms from first line drug treatments like beta blockers and calcium channel blockers.
  • Exercise:  Exercise is beneficial to patients with HCM and has not been associated with increased risk of ventricular arrhythmias as previously feared and reflected in prior guidelines which urged caution with regard to exercise. Current research reflects the cardiovascular benefit to all, including HCM patients, of moderate exercise.  However, it is critical to seek input from HCM experts and engage in shared decision making about the risks and benefits of exercise before undertaking an exercise program. This discussion should be repeated at regular intervals.
  • Shared Decision Making:  The 2020 and 2024 guidelines emphasize the process of shared decision-making between patients and medical providers.  Medical providers should provide an overview of all testing and treatment options, and engage the patient in a complete discussion of all risks and benefits.  Most importantly, the patient is encouraged to share their own goals, values, and concerns which should inform the final decision.
  • Referral to HCM Specialty Centers Encouraged:  Referral to specialized HCM Centers with expertise in treatment of the disease is important.  Expert advice is especially important where the treatment path is not clearly defined, or for HCM specific procedures and complex treatment and lifestyle decisions.
  • Atrial Fibrillation:  HCM patients with atrial fibrillation, whether it is persistent or paroxysmal (sporadic), have a heightened risk of stroke. Therefore, there should be a low threshold for prescribing anti-coagulant drugs for HCM patients with AFib without regard to traditional stroke risk scoring systems, i.e. the CHADS-VASc score.  Maintenance of sinus rhythm and rate control are key treatment goals.

For key patient takeaway messages from the guidelines click HERE.

For a complete look at the guidelines click HERE.

For a video of the Writing Committee Chair Dr. Steve Ommen and Co-Chair Dr. Carolyn Ho talking about the new guidelines, as well as other and related resources, click HERE.

Is Aficamten the Blockbuster Drug Cytokinetics is Hoping For?

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Cytokinetics today released positive results from Sequoia-HCM, its Phase 3 clinical trial of the experimental drug aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).  Patients treated with aficamten showed significantly increased exercise capacity as demonstrated by a 1.74 point increase in peak oxygen uptake (pVO2) measured during cardiopulmonary exercise testing.  Improvements were also seen in provoked outflow tract gradients, and most importantly, patients felt better.  

The study had enrollment of approximately 300 patients who were followed for 24 weeks. 

Aficamten was well-tolerated, adverse events were comparable to those taking a placebo, and importantly, there were no instances of worsening heart failure or treatment interruptions due to low left ventricular ejection fraction (LVEF).

According to an article in Med City News, the drug may have an advantage over the Bristol Myers Squibb drug mavacamten (sold under the brand name Camzyos) because there were no reports of worsening heart failure. In the Phase 3 EXPLORER trial of mavacamten, seven patients in the treatment group experienced reductions to their LVEF.  

Based on the projected success of aficamten, Cytokinetics stock price jumped by 83% and the company is said to be the subject of takeover interest from AstraZeneca and Novartis.

Cytokinetics plans to apply for FDA approval for the drug in the second half of 2024.

Complete results from SEQUOIA-HCM will be presented at an upcoming medical conference.

You can read more about the drug in these previous articles on HCMBeat:

Cytokinetics Teases Upcoming Phase 3 Aficamten Trial in nHCM

Promising Data about Aficamten Presented at Meetings

Aficamten Updates from Cytokinetics

More on Aficamten & Mavacamten from ACC 2022

Aficamten Gets “Breakthrough Drug” Status from FDA

Cytokinetic’s Drug Aficamten & Upcoming HCM Summit – Interview with Dr. Martin Maron

Results Published from REDWOOD-HCM Phase 2 Trial

The Future of HCM Treatment

 

 

 

 

 

 

Mavacamten (Brand Name Camzyos) Approved in Europe

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Bristol Myers Squibb’s first-in-class myosin modulator mavacamten (brand name Camzyos) has been approved by the European Commission for the treatment of obstructive hypertrophic cardiomyopathy in all countries which are part of the European Union.

See the press release here.

Septal Reduction – Not a One Size Fits All

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A recent article published in the European Journal of Cardiology Heart Failure compares septal myectomy to septal alcohol ablation. The paper goes through specific factors which make one procedure or the other more appropriate: individual anatomy and age being two .of the most important.

The article emphasizes that proper patient selection for either procedure is key.  Further, it emphasizes the necessity of having both procedures done at at high volume center in order to increase the odds of a successful procedure.

Mavacamten Approved in Canada

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Bristol Myers Squibb’s first in class drug  mavacamten (brand name Camzyos) has been approved by Health Canada for the treatment of obstructive hypertrophic cardiomyopathy.

Longer Term Results for Mavacamten

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The VALOR-HCM trial  was a Phase 3 clinical trial which compared the Bristol Myers Squibb drug mavacamten (brand name Camzyos) to septal reduction therapy (myectomy and septal alcohol ablation) over a 16 week period.  At the end of the 16 week period, the patients originally randomized to the placebo were prescribed mavacamten, while those originally prescribed mavacamten continued taking the drug for an additional 16 weeks for a total of 32 weeks

At last weekend’s American Heart Association meeting in Chicago and simultaneously published in Circulation, lead investigator Dr. Milind Desai of the Cleveland Clinic announced that after 32 weeks of mavacamten treatment, patients continued to see positive cardiac remodeling, as well as improvement to left ventricular outflow tract gradient, diastolic function and quality of life. This ultimately allowed a whopping 88% of patients enrolled in the trial to avoid a septal reduction procedure. 

Similar results were noted in those patients who began mavacamten after an initial 16 weeks on a placebo.

This is good news for HCM patients!

The Future of HCM Treatment

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Doctors from the University of Pennsylvania this week published an overview of current therapies available for the treatment of HCM.  While this article mentions all of the old standards – beta blockers, calcium channel blockers, myectomy and alcohol ablation, the real focus is on the future of HCM treatment. In particular, the article describes several new and/or experimental therapies which look promising for the future.

Continue reading “The Future of HCM Treatment” →

Mavacamten vs. Septal Reduction – VALOR-HCM Trial Results Published

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The VALOR-HCM trial results have just been published in the Journal of the American College of Cardiology. 

This study enrolled 112 obstructive HCM patients for a 16 week double blind trial of the drug mavacamten (brand name Camzyos). All patients in the trial had been referred for septal reduction therapy – either septal myectomy or septal alcohol ablation – to treat their highly symptomatic obstructive hypertrophic cardiomyopathy.   The researchers looked at whether the addition of mavacamten to their other drugs would improve their symptoms enough so that they no longer met the criteria for septal reduction therapy (SRT) under the 2011 ACC/AHA Guidelines.

You can read many more details about the VALOR-HCM study here in this recent blog post on HCMBeat.

Continue reading “Mavacamten vs. Septal Reduction – VALOR-HCM Trial Results Published” →

FDA Approves Mavacamten under Brand Name Camzyos

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At long last, there is a FDA approved drug specifically intended for the treatment of hypertrophic cardiomyopathy.  After several years of testing, and based on the results of the groundbreaking EXPLORER-HCM trial, Bristol Myers Squibb’s new drug mavacamten, being marketed under the brand name Camzyos, is now available to HCM patients.

Continue reading “FDA Approves Mavacamten under Brand Name Camzyos” →