Positive clinical trial endpoints for MAPLE-HCM study announced by Cyctokonetics for aficamten in obstructive hypertrophic cardiomyopathy

In the third of a series about decision-making and risk in HCM, Gordon Fox explains where risk data comes from and how to understand it.

In part three of this series on decision making in HCM, Gordon Fox discusses how medical professionals define risk within a patient population, and what the different kinds of risk mean for a patient.

I do not claim to be a political expert, but I do know what I am - a passionate patient advocate who has seen how systems can work for and against patients, and someone willing to put thought into action, to create a plan to make healthcare safer for a population that has long been ignored and at high risk. As we prepared to take 30 patient advocates to Capitol Hill to discuss matters of importance to the community, we monitored the activities inside Washington DC. The floor kept shifting under us week after week as we attempted to prepare a cohesive message attached to policy that had a good chance of both being bipartisan and moving forward. Please go back and look at your news headlines between the beginning of February and the end of March - it was chaotic, and it sometimes appeared schizophrenic. But we had to keep searching for areas in which we could find some base definition of what it means to be a citizen or resident within the United States. There is a slow, simmering issue that has had my attention since approximately 2007, something that reaches beyond the borders of cardiac disease but gets to the very core of our shared humanity. We will all certainly need a medication, a supplement, or a food additive to ingest into our bodies at some point in time. In the late 2000s, Dr. Harry Lever of the Cleveland Clinic brought something to my attention - an observation about generic drugs not functioning in a predictable manner. To say we've talked about this hundreds of times would be a gross understatement, it's more like thousands of times over nearly two decades. You see, Harry Lever is a really unique mix of old school cardiologist and Detective Columbo, always searching for clues to the puzzle to unravel and find the bad guy. Harry and I shared observations about patients with HCM who had previously appeared stable, with no comorbidities, no lifestyle changes, no recent domestic or workplace stressors - things seemed really normal for these people, yet their symptoms vastly changed nearly overnight in some cases. Over the years other drug quality problems had come to my attention, including deaths related to a heart transplant medication I take, called tacrolimus. Eventually Harry put me in contact with other individuals who also were sharing our observations. There was a radio show producer named Joe Graedon, a researcher in Utah, named Erin R. Fox, and a pharmacist by the name of David Light. David and I had spoken a number of times and he shared with me some of his scientific findings which were quite alarming. I learned of the process of “dissolution” and how different molecules responded differently to the dissolution process and thereby would absorb differently within your body. This impacts the mechanism of action which, in my case, was to keep my heart protected from my body attacking it as a foreign entity. I learned of the problems with generic drug manufacturers through the writings of Katherine Eban ( Bottle of Lies , Harper Collins ecco, 2019 ), and Rosemary Gibson, ( China RX , Prometheus, 2018) an advocate on behalf of patient safety on multiple planes within the ecosystem. This small band of advocates is trying to sound an alarm throughout the country. Now it is time for the productive and equitable deployment of the shared efforts to keep every one of us safe and healthy. That is what we went to Capitol Hill to talk about. There is a mechanism within the National Defense Authorization Act, a piece of legislation that is voted on each year to provide funding for our national defense. It is a type of legislation that typically moves unopposed through the process as we all seek to have a strong national defense. Within this act we are advocating the Department of Defense to support the NDAA amendment “Transparency and Quality in Pharmaceuticals Act,” to support the proposed ARPA-H project “Create and Deliver Actionable Transparency to Drug Quality.” We encouraged the VA to join with the DoD project and drug procurement reform efforts. 2025 VA Appropriations language already present in House section “Prescription Drug Quality” and Senate section “Drug Quality Scoring,” and the FDA to use DoD drug quality data to further inspect “red” rated manufacturers and reward “green,” to set a “zero toxins goal” in medicines similar to EPA’s goals for water and air, and to work collaboratively with independent testing efforts similar to Europe’s approach. Lastly, we encouraged the NIH to research drug quality to better identify issues, their public health impact, and strategies to best address them. So, as we walked around Capitol Hill inviting legislators to come join us at a briefing to learn more about these initiatives. We had meaningful discussions with various members of each office’s internal administration. We spoke to legislative assistants, healthcare advisors, defense advisors, Legislative Directors, Deputy Chief of Staffs, and Health Policy Advisors. In total we met with 24 offices. This and the briefing offered them a deep appreciation for the community we are and the problem we seek to solve - primarily the quality of generic drugs in the United States. Secondarily, we spoke of step therapy and prior authorization and the meaningless waste of time, effort, money and life quality by delays costing 1.3 billion dollars a year in waste fraud and abuse. The waste and fraud is being perpetrated upon healthcare systems, physicians and patients as we waste our time and precious resources playing a game that serves no one and costs, time, money and frankly the reputation of the health insurance systems themselves. It's time for us all to be reasonable adults; to fix the problems that we know are fixable and stop fighting about the differences in how to do it. Let's start negotiating how we all can benefit from better health systems and better access to safe high-quality low- cost generic drugs. If there is anybody who has an argument as to why anything I have said about these issues is not good for all Americans, I welcome the conversation. Let's talk it out and understand how we can see the world with such different philosophies.

Greetings to all of our Bighearted friends, We have certainly had an eventful April and there are many updates in this letter to bring you up to speed. I hope everybody had a joyful holiday season and we're able to spend time with friends and family. April completed our second visit to Capitol Hill in very interesting times. I am happy to say that the offices we met with, including Senators Tim Scott (R-SC) and Patty Murray (D-WA), Representatives Alexandria Ocasio-Cortez (D-NY), and Pete Session (R-TX), were attentive and responsive to our requests. Our focus on the topic of generic drug quality struck a cord with all offices in this completely bipartisan effort. Having meaningful conversations about the burdens of step therapy and prior authorizations really help to invigorate the staff members we met with to be prepared with strong legislation that can be widely accepted and instituted. I encourage you to take some time and watch our Hill briefing on our YouTube channel . View photos in our Gallery . We were able to secure a champion for a federal HCM Awareness Day as well as a move for appropriations for the HEARTS Act of 2024, H.R. 6829*, which was signed into law by the President on December, 20,2024. I can safely say that our trip to Capitol Hill was successful and meaningful. I wish to extend my gratitude to our entire internal HCMA team and our volunteers and industry partners. Bringing a true patient voice to our government officials is the most effective way we can advocate for changes that are beneficial to all those with chronic disease, cardiac, and otherwise. Then we were on the road to Orlando with our dear friends at AdventHealth, conducting a patient education symposium. It was wonderful to see so many Bighearted friends, it feels like family. There were so many deeply emotional moments of the weekend, including reuniting Lorianne Peachey with her plasticized human heart and watching she and her husband marvel at the thing that brought them so much love, joy and pain. Holding your own heart in your hands is something only a few have experienced. My sincere gratitude to Lori for sharing her heart with us all. We were able to go visit Brian Wolski, who was unable to attend the session because he was awaiting a heart transplant and day passes out of the hospital are really not a thing. However, the weekend became quite eventful as just a few hours after Stacy and I visited with Brian and Cassie at AdventHealth after 369 days Brian received the call that a heart had been secured for him. As I write this letter today, he is post-op and recovering well. I also had the opportunity to hug people I have known for 20 plus years but have never previously met, and those are beautiful moments. Our educational content was fantastic. I am so impressed with how AdventHealth has grown into such a robust and high quality program. My thanks Dr. Marcos Hazday, MD FACC,and all the speakers at AdventHealth and Debbie Moore, BSN, MS, RN, Sarah Blair, Tracy Demetree, Kelly Reilly, Steven Kelley, Cheryl Hammerly and Lorianne Peachey with a special thank you for handling logistical challenges at the last moment. A special shout out to Steven Kelley and Janet Gruer for their volunteerism, and being the boots on the ground HCMA representatives for the meeting. This model worked out so well that, when we come to your town next, you'll have the opportunity to step up and give us a hand. In the middle of the chaos of this month, a staff member who is also my niece lost her father. Her father was my sister Lori's first husband. As families we know divorce and separation change dynamics. There was a time that John Titus Jr., my niece and nephew's father, was a young charismatic man who stole my sister's heart and. for a period of time made her very happy. For that I will be forever grateful to John Titus Jr. My sincere condolences to my niece and nephew, John and Stacy, and their sister Heather, as they grieve the loss of this rather complicated man. And our staff deserves two special shout outs this month – to Julie Russo our Legislative Lead, who really helped make Hill Day a success and to Stacey for navigating this month with grace and professionalism. Together we can build better systems to improve and save lives, cost effectively and with equity for all. * https://www.congress.gov/bill/118th-congress/house-bill/6829 Best wishes, Lisa

Medical Management means using medicines and other non-invasive therapies to relieve symptoms of hypertrophic cardiomyopathy and other thick heart diseases. Knowing what is out there and what is being studied will help you navigate your treatment with your healthcare providers.

Part 2 of a series on making decisions in HCM. A key reason is that decision making is so difficult is that most decisions involve more than one risk.

Bristol Myers Squibb announces that Camzyos has been approved for Obstructive Hypertrophic Cardiomyopathy in Japan.

U.S. Food and Drug Administration Updates CAMZYOS® (mavacamten) Label to Reduce Echocardiography Monitoring Requirements and Contraindications for Obstructive HCM

It is hard to believe the first quarter of 2025 is in the history books. In the space of hypertrophic cardiomyopathy and thick heart muscle disorders, the distance between the promise and the delivery of a reality freed from burden of disease is closer than it has ever been, not only in the United States but throughout the world. Unfortunately, we are navigating through some challenging health policy times, which will impact a large percentage of those with the diseases we seek to serve. While we navigate these challenging waters together, we remain committed to ensuring safe, accessible, affordable healthcare while ensuring the rights of those with disabilities are maintained. Last month, I attended two large conferences - one held in Stockholm, Sweden the other Chicago, Illinois. The research communities worldwide are holding their breath, waiting to see how we will move forward, even as we continue to develop new therapies, treatments and, even potentially, cures. It has never been more important to keep research moving, as we are so close to so many amazing improvements in our ability to care for those with thick heart muscle disorders, including HCM in all its forms, Amyloidosis, Fabry’s disease, Danon disease, and RASopathies. There was amazing science presented at the American College of Cardiology, where we warmly welcomed new president, Dr. Christopher Kramer, the original director of the hypertrophic cardiomyopathy center at University of Virginia. We look forward to his leadership and wish him well in his challenging tasks ahead. Later this month we will be in Orlando, Florida - please register and join us for this wonderful Bighearted warrior tour in person with our friends at AdventHealth and the incomparable Dr. Marcos Hazday. I even understand that there's some carpooling being organized from the Tampa area. If you're interested, reach out to the office and we will connect you. Maybe, the most impactful thing that will happen in the month of April is that we will conduct our second visit to Capitol Hill. Our lead topic this year is something you have heard us talk about at many prior meetings of the HCMA and podcasts; the generic drug quality issue. We are proud to be partnering with David Light, Co-founder and President of Valisure, and retired Colonel Vic Suarez, to ask House and Senate members to support the inspection of all generic drugs purchased by the Department of Defense and the Veterans Administration and make results of these inspections open for public use. Secondly, we are seeking rational oversight of health insurance companies’ abuse of prior authorizations and step therapy requirements. These issues cost an estimated 1.3 billion dollars a year and provide nothing to keep a patient safer or a physician's office running more efficiently. Common sense tells us to not waste money where there is no return. Additionally, prior authorizations and step therapies can keep patients sicker longer, ultimately costing the healthcare system more money. Our briefing will educate Representatives to act in an informed manner when moving policies that impact us all. You can watch the video of our briefing from Wednesday, April 9th on Vimeo: https://vimeo.com/event/5043266 If you wish to get involved or more informed on any of the issues above, I encourage you to visit the website, 4hcm.org , or reach out to the office and the staff will be happy to assist you. On the day before I head out to Washington DC, I will leave you with this one thought - we have come a really long way in our understanding of HCM over the past 60 years. We have increased the lifespan of those with HCM, through collaborative research and implementation of best practices in an organized fashion throughout this country. We have worked so hard to end suffering for so many, and we are succeeding in our shared goal to outsmart hypertrophic cardiomyopathy and other thick heart muscle disorders. It is important to continue the research into all aspects of these diseases, including the biological, the clinical, and burden of disease measurements. System improvements, positive impact of timely diagnosis and treatment, and the value to society of all of these big hearts being here, will help keep their families whole. So we're off to DC to try to educate others about what it really means to live in our ecosystem. Best wishes, Lisa

This first in a series post about making decisions as you navigate living with HCM, focuses on the three steps of decision-making: Identification, Analysis, Evaluation.