Adaptable approach augurs well for Cytokinetics - even after a CRL

US biotech Cytokinetics (Nasdaq: CYTK) is seeking to develop medicines that treat cardiovascular and neuromuscular diseases of impaired muscle function.

The company’s research is focused on modulating proteins in the sarcomere, the fundamental unit of muscle contraction found within muscle cells.

These proteins are seen as key to unlocking the potential treatment of diseases caused by impaired muscle function.

Innovative research and resilience

In recently celebrating its 25th anniversary, Cytokinetics was able to reflect on the progress the company has made as a pioneering modulator of muscle function, even if that means learning from and adapting to a few challenges along the way.

Cytokinetics’ recent achievements include reaching late-stage clinical development with two candidates and taking another two into the lab. But innovative drug development is not without risk, even when a company is confident in its approach.

So Cytokinetics has adopted a pragmatic strategy, meaning that when one of its lead candidates suffered a recent setback, another highly promising drug was there to take pole position.

In February of this year, the US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the company’s New Drug Application for omecamtiv mecarbil, an investigational, selective, small molecule cardiac myosin activator, for the treatment of heart failure with reduced ejection fraction (HFrEF).

The FDA was not convinced that GALACTIC-HF - a Phase III trial of omecamtiv mecarbil in HFrEF patients at risk of hospitalization and death, despite being treated with standard-of-care therapy - establishes enough evidence of effectiveness, meaning an additional trial is required.

'Parallel programs'

But Cytokinetics is not planning a further trial of omecamtiv mecarbil and the CRL did not prompt a mass abandonment by investors or force it to lay off employees, as can occur with single-asset biotech companies.

This is because the company is now fully focused on another opportunity - the development program for aficamten, the next-in-class cardiac myosin inhibitor, which is currently the subject of SEQUOIA-HCM, a Phase III trial in patients with obstructive hypertrophic cardiomyopathy (HCM).

“We always thought of developing parallel programs,” Fady Malik, executive vice president, R&D, told The Pharma Letter. “We’re still optimistic on omecamtiv mecarbil’s future. We continue to have discussions with the FDA on that, we filed an application with the European Medicines Agency, also in China. We continue to think about how it may someday make it to patients.

“But after the CRL, aficamten became the lead.”

Cytokinetics has completed enrolment in SEQUOIA-HCM and expects top-line results by the end of the year. The company has also initiated enrollment in MAPLE-HCM, a Phase III trial comparing aficamten and metoprolol in obstructive HCM, while ACACIA-HCM, a Phase III study of aficamten in Non-Obstructive HCM, is expected to start next month.

'Very special medicine'

Dr Malik described aficamten as “a very special medicine” with the potential to keep patients out of hospital as well as feel and function better, profoundly impacting their lives.

“In HCM, we will be second to market - competition is good for patients and good for the market,” he said. “It’s viewed as transformative on the disease. Over time, it could be potentially disease-modifying.”

Deeper in the pipeline, Cytokinetics has CK-586, a cardiac myosin inhibitor in development for heart failure with preserved ejection fraction, and CK-136, a cardiac troponin activator for heart failure. Both are in Phase I trials.

Cytokinetics has high expectations for both and will apply lessons from past setbacks, which also include the late-stage failure of the fast skeletal muscle troponin activator reldesemtiv in amyotrophic lateral sclerosis, as it moves its candidates closer to market.

'Fruits of work' to come in next year or two

Having started preparations for the commercialization of omecamtiv mecarbil, the company has been able to shift this focus to aficamten, which it plans to launch alone in the USA and Europe. The firm expects to partner with other drugmakers to take it to market elsewhere, and it already has a partnership in China with Ji Xing Pharmaceuticals to achieve this in the Asian country.

The company’s five-year vision includes plans to introduce marketed products and advance the pipeline. Financial independence is another objective for the near term as revenues start to come in.

“Our ambition is to become a fully integrated biopharmaceutical company, Dr Malik said. “We have recently hired a head of Europe, we will also bring in a head of market access and another position.

“We have been doing innovative research in the cardiovascular area and our focus in muscle biology. It’s been a journey, but we are seeing the fruits of this work in the next 12 to 24 months.”