MSD and Bayer launch big gamble on heart failure candidate

The first patient has been enrolled in a pivotal phase 3 study of Merck Sharp & Dohme and Bayer’s vericiguat, a pipeline treatment for patient chronic heart failure with reduced ejection fraction (HFrEF).

The large scale trial represents a major gamble for the companies, however, as a previous phase 2 study failed to meet its primary endpoint.

The field of heart failure treatment is currently enjoying renewed interest and investment, most notably led by Novartis’s newly launched Entresto.

Bayer and MSD want to tap into the same market of HFrEF patients with vericiguat, a first-in-class soluble guanylate cyclase (sGC) stimulator.

Now the companies are ready for a big push into phase 3, and plan to recruit 4,900 patients at 530 centres in 39 countries around the world.

The study is expected to take over three years (39 months) to complete, at the end of which the companies hope to have a major new treatment on their hands. However analysts have been sceptical about the drug’s chances until now - but any drug which can prove real benefits would secure multi-billion revenues.

The primary efficacy outcome is the time to first occurrence of the composite endpoint of cardiovascular mortality or HF hospitalisation in patients with deteriorating chronic HF with reduced ejection fraction.

The companies were convinced to press ahead with the drug, despite their phase 2 trial SOCRATES-REDUCED in 456 patients with HFrEF failing to meet its primary endpoint. This goal was to reduce N-terminal pro-B-type natriuretic peptide (NT-proBNP) in stable patients with worsening chronic heart failure and reduced ejection fraction when all doses were combined.  However the trial did suggest safety and efficacy in patients taking the highest dose, 10-mg, and VICTORIA will pursue this signal.

"Currently, one in five people worldwide are expected to develop HF in their lifetime. With the novel compound vericiguat, Bayer and MSD are pursuing a new research approach in this field," said Dr. Jörg Möller, head of Bayer's pharma drug development. "We are excited about vericiguat being the first sGC stimulator to be evaluated in patients with chronic HF."

The burden of heart failure (HF) is enormous and increasing, with millions of patients surviving heart attacks, but living on with damaged hearts which progressively weaken. Heart failure mortality is worse than some cancers - between 17% and 45% of patients die within one year of hospitalisation for an acute HF event.

A number of other companies are developing new treatments for HF.  Earlier this month, Amgen announced that it will advance its cardiac myosin activator omecamtiv mecarbil into phase 3. The candidate has been developed with Cytokinetics, which showed benefits to cardiac function in its COSMIC-HF phase 2 study.

Bayer has another HF candidate in phase 3 - finerenone moved into late stage trials last year, and is being studied in patients with HF and type 2 diabetes and/or chronic kidney disease.

Despite some compelling trial data, however, Entresto hasn’t yet taken off commercially, with Novartis presenting disappointing revenues since it was launched last year.