After 27 years in business, Cytokinetics hopes to pit its own cardiac myosin inhibitor against one it initially developed—now owned by Bristol Myers Squibb—in a market worth billions. Aficamten has a PDUFA date of Dec. 26.
Cytokinetics is anticipating a late Christmas present: an approval for a potential blockbuster.
The FDA action date for the company’s obstructive hypertrophic cardiomyopathy (oHCM) molecule aficamten is December 26. An approval would mark the first in the U.S. under Cytokinetics’ own name after 27 years in business.
Cytokinetics is, in a way, competing with a former version of itself. The most recent novel treatment on the market for oHCM—an inherited disease that causes thickening of the heart muscles, which in turn causes shortness of breath, dizziness and chest pain—is BMS’ Camzyos. Cytokinetics helped develop Camzyos in-house and spun its development off to a separate company, MyoKardia, which BMS bought in 2020 for $13.1 billion.
Camzyos was approved in 2022 and brought in more than $600 million for BMS in 2024. When it first acquired MyoKardia, BMS said Camyzos could earn $4 billion in sales at its peak, according to Cytokinetics CEO Robert Blum. “And they’re on their way,” he told BioSpace.
If aficamten also captures a preferential share of the HCM market, analysts say it could bring in $4 billion at its peak as well, Blum added, and potentially as much as $10 billion if Cytokinetics’ vision for future expansions eventuates.
“Twenty-seven years ago, we embarked on this journey of developing inhibitors of cardiac disease,” Blum said. “Commercialization has been our plan since day one.”
Building a Better Camzyos
Cytokinetics was founded back in 1998. But despite taking nearly three decades to get near its first FDA approval, it has all been according to a methodical plan, Blum said.
“Unlike other biotechs that graft a revenue plan onto an R&D plan, we’ve been planning both all along. We shouldn’t expect an ‘autoimmune rejection’” of the revenue plan, he added.
Both Camzyos and aficamten are cardiac myosin inhibitors—meaning they block the action of the muscle protein myosin inside the heart, counteracting the effects of oHCM.
“Think about the heart ejecting blood like a garden hose,” Fady Malik, EVP of research and development at Cytokinetics, told BioSpace. In patients with oHCM, flow through the garden hose is pinched and the blood therefore has less space to move through, he explained. The heart requires much more pressure to move blood, which in turn increases pressure in the lungs, causing shortness of breath. Normal activity such as walking uphill, can become extremely difficult.
Many patients take beta blockers, which don’t always work well, Malik said. Others undergo a myectomy, where a surgeon removes thickened heart tissue. In advanced cases, patients may require a heart transplant.
When Camzyos was approved in 2022, Cytokinetics had already been planning its successor for some time. “We conceived of the idea that [aficamten] might be beneficial for patients” 10 years ago, Malik said, and the company has been developing the drug to best Camzyos ever since.
While the same class of drug as aficamten, Camzyos has a variety of drawbacks, according to Malik and Blum. The first is a slow rate of action; patients need to have their dosage checked every month for the first three months of treatment, which makes achieving the correct dose a protracted process. Secondly, because titration is also slow, if a patient overshoots the target dose, they might need to interrupt treatment altogether, as adjustment would take too long, which itself would be dangerous, Malik said.
Aficamten, on the other hand, can be titrated every two weeks. The drug’s more rapid cycling enables patients who overshoot the target dose to simply titrate down, the executives explained.
In March 2023, Cytokinetics shared data from the Phase III MAPLE-HCM trial, showing that patients on aficamten had higher exercise capacity, while those in the control arm receiving standard of care beta blockers saw their exercise capacity decrease.
Analysts at Truist Securities at the time called the results potentially “best-in-class” and supportive of a first line setting for the drug. Camzyos, on the other hand, flunked a Phase III trial in April, unable to improve symptoms or exercise capacity after 48 weeks in patients with non-obstructive HCM.
Expansion Plans
On Wednesday, Cytokinetics announced an early win for aficamten, with its approval in China for oHCM. The nod triggered a $7.5 million milestone payment from Sanofi, which owns the rights to the drug there.
The market for oHCM alone is about $1 billion per year, according to Blum. But Cytokinetics has its eyes on non-obstructive HCM as well and is hoping to corner the entire HCM market, which Blum said could balloon sales to a total $10 billion annually. Aficamten improved symptoms in a Phase II trial in non-obstructive HCM, Cytokinetics reported in March 2023, and the company is continuing to test it in the indication in the Phase III ACAIA-HCM study.
Stifel analysts say the company has a shot.
“We think [Cytokinetics] has a very credible chance to be the only drug available for the entire HCM spectrum,” they wrote in November after Cytokinetics’ third quarter earnings report.
However, not everyone agrees on just how much money Cytokinetics is set to make. Truist analysts writing to investors on Wednesday after the China approval, modeled $3.4 billion in peak revenue for aficamten in oHCM, and an additional adjusted peak revenue of $460 million for the asset in non-obstructive disease.
Partnering could be a source of revenue for the company. Blum made it clear that Cytokinetics wants to go to market with aficamten itself in the U.S. and Europe, but said the company could seek partners for commercializing the drug in the rest of the world.
Addressing rumors that Cytokinetics had been in talks to be purchased by another larger pharma, Blum said that the deal just did not come to fruition. “We thought we had agreed upon a deal with another party on being purchased, but that party walked away. We went back to plan A.”
If another opportunity like that comes back around, he said Cytokinetics will “do the right thing for shareholder value.”
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