Omecamtiv Mecarbil

It has taken nearly 30 years, but Cytokinetics is on the cusp of its first-ever approval. Wall Street regards aficamten — a once-daily pill for a heart condition — as a future blockbuster, and many will be watching closely to see how much of a success the biotech can make of its first foray into the commercial sphere. The drug’s journey was not straightforward. It is intended to treat obstructive hypertrophic cardiomyopathy (oHCM), a disorder in which the heart muscle becomes thickened, impairing contractility. The coming FDA approval decision, due by Dec. 26, is based on data from a trial called SEQUOIA-HCM, which emerged two years ago and were good enough to spur talk of a takeover. A year or so later, Novartis was rumored to be interested in buying Cytokinetics. But that deal did not materialize, and the biotech has been unable to score even a partner for aficamten in Western markets. It then fumbled aficamten’s approval application, failing to include a patient safety program in its submission despite this being widely expected. The FDA demanded one in May, delaying the approval decision by three months. And now, Cytokinetics finally has its chance to make good. It even has opportunities to expand the drug’s label in the near future. But launching alone won’t be easy. Aficamten will compete with Bristol Myers Squibb’s Camzyos, which has been on sale for over three years . Both drugs inhibit cardiac myosin, a muscle protein in the heart. “How can a company that’s never ever made it to the finish line, now actually get to the finish line and kick ass, just based on how their drug and their label from the FDA could be different?” B Riley equity analyst Mayank Mamtani said in an interview. The good news is that aficamten’s label probably will be differentiated from Camzyos’. Patients on Bristol Myers’ drug must undergo ultrasound imaging of their hearts every three to six months, since it can cause heart failure due to systolic dysfunction. They must also be checked for drug-drug interactions. Camzyos is metabolized via the same pathways as a host of other drugs , meaning that if a patient takes them together, Camzyos will not be broken down as fast. That increases heart failure risk. “With aficamten, we were careful to ensure that it was metabolized through different pathways, so if one got blocked, there were other pathways to metabolism,” Cytokinetics head of R&D Fady Malik told Endpoints. The drug had no common clinical drug interactions in its trials, he added, “and we hope on the label not to have them.” A cleaner label would give aficamten an edge in the market. But kicking off its first-ever drug launch without a partner could be a stretch for Cytokinetics. “[Cytokinetics has] been hiring very, very aggressively, raising a lot of capital. I think that resources-wise, they are very well-funded to execute on the launch, to compete versus Bristol,” Mamtani said. “But still, just from a perception standpoint, it’s always that David versus Goliath.” Aficamten is licensed to Sanofi for China and Bayer for Japan, and approval in these countries, expected in 2025 and 2026, respectively, will trigger milestone payments to Cytokinetics. Cytokinetics has another deal centered on aficamten. In 2024, it restructured a deal with Royalty Pharma so that Royalty will receive 4.5% of annual sales of aficamten up to $5 billion, and 1% above $5 billion. In return, Cytokinetics got $50 million upfront and the chance to draw an additional $175 million within a year of aficamten’s approval in oHCM. Cytokinetics’ shareholders were not delighted . Even now, it is fair to say that at least some of Cytokinetics’ investors would rather the company had a partner for Western markets. Aficamten is due a European approval decision early in 2026, and Mamtani points out that European launches tend to be more complicated than a US debut, as the drug’s price may have to be negotiated separately in each country. Admitting that Cytokinetics launching by itself is “somewhat unusual,” Cytokinetics CEO Robert Blum told Endpoints he believes the company can build a business in Europe, “if we do it in a gated, prudent way.” He said that the launch in Germany is planned for the first half of next year. On the other hand, there could be a downside to a licensing deal, Mamtani said. “If you do give away your European rights, then you’re not really an unencumbered company anymore. So you become less attractive, to some extent, from a strategic or an equity investor standpoint. You’ve diluted a little bit of the economics,” he said. Could a buyout, then, still be a possibility? Mamtani said several large drugmakers are facing the loss of exclusivity on some of their big sellers and are under pressure from shareholders to do a deal. And Cytokinetics could be “a very easy plug-and-play to be having in your portfolio.” However, Camzyos might stand as a warning to companies considering acquiring Cytokinetics. Obtaining it was the rationale behind Bristol Myers’ $13 billion acquisition of MyoKardia in 2020, but the drug never sold quite enough to justify the MyoKardia buyout. “Bristol overpaid for MyoKardia. I don’t know if they can ever recoup that,” Mamtani said. A buyout of Cytokinetics would likely cost a similar amount as the MyoKardia deal. But at this point, any buyers are likely to wait and see how fast aficamten takes off in the market. “It’s not that we’re not considering [a deal], we do. But we also are not beholden to it,” Blum said. Asked whether a takeover would be easier than Cytokinetics remaining independent, Blum replied, “We’ve never opted for the easiest path.” Regardless of how the initial launch of aficamten plays out, Cytokinetics might be able to boost it a year or so later. This summer, the company scored clinical data proving the drug to be superior to beta blockers , currently the first-line therapy for oHCM. Cytokinetics intends to add this data to aficamten’s label once the initial approval is granted, and this could occur next year. But sales might only increase gradually, Blum said. “Payers may be initially resistant because beta blockers are cheap. So what you may see is that physicians move patients through beta blockers more rapidly in order to get to a cardiac myosin inhibitor, and preferably aficamten,” he said. “It’ll take some time to change practice patterns.” A future trial readout could allow yet another expansion — and another advantage over Camzyos. Aficamten is in a trial called ACACIA-HCM in the milder, non-obstructive form of HCM, with data due in the second quarter of 2026. Crucially, Camzyos’ trial in this form of the disease failed, so aficamten could have a clear run at this population. Non-obstructive HCM affects around 100,000 people in the US, Blum said, roughly as many people as the obstructive form. But all this is in the future. First, Cytokinetics must pull off an impressive solo aficamten launch. The drug’s price will be a major consideration. “We think that BMS has established a market price,” Blum said, adding that Camzyos sells for around $100,000 per patient per year in the US. “We’ll price in and around. Whether that’s at a modest premium or a modest discount, we’re not saying.” Cytokinetics cannot bank on sales from other products for some years. Its next most advanced candidate, a heart failure med called omecamtiv mecarbil, is in Phase 3 but is not expected to reach market until 2028 at the earliest. It could take even longer for the company to reach profitability. Blum declined to give a date at which the company might break even, but according to B Riley analysts’ forecasts, Cytokinetics will become profitable in 2029. Jefferies analysts forecast Cytokinetics’ first profit in 2030. A lot is riding on aficamten. Editor’s note: This article has been updated to clarify that aficamten is a once-daily pill.