Bayer and Merck & Co/MSD have filed for approval of their first-in-class drug for chronic heart failure (CHF) – vericiguat – in the EU and Japan, setting up approvals next year.

The filings are based on results of the 5,000-patient VICTORIA study – the first pivotal trial of an oral soluble guanylate cyclase (sGC) stimulator – which showed that vericiguat reduced the rate of cardiovascular deaths and hospitalisations among patients with worsening heart failure and reduced ejection fraction (HFrEF) by 10% compared to placebo.

sGC stimulators are thought to work by correcting a dysfunctional nitric oxide signalling pathway seen in heart failure.

Bayer and MSD’s decision to take vericiguat into a phase 3 programme in 2016 raised eyebrows among industry watchers, given decidedly mixed results in the phase 2 SOCRATES-REDUCED trial that had some analysts describing the move as a bit of a gamble.

The bet seems to have paid off, although the jury is still out on just how big a product vericiguat will be as the CHF market evolves. When VICTORIA started, Novartis’ Entresto (sacubitril/valsartan) had only just started to roll out onto the market and was growing slowly, despite being the first new drug for CHF for many years.

Since then the landscape of CHF treatment has changed. Entresto crossed the blockbuster sales threshold in 2018 from its use in HFrEF, although Novartis’ hopes of expanding its use in heart failure with preserved ejection fraction (HFpEF) took a knock last year with the results of the PARAGON-HF trial.

HFpEF accounts for at least as many heart failure patients as HFrEF but currently has no approved therapies.

Meanwhile, this year saw the first approval of an SGLT2 inhibitor for CHF when AstraZeneca got a green light from the FDA for Farxiga (dapagliflozin) as a treatment for HFrEF in patients with and without type 2 diabetes.

The approval is based on stellar results in the DECLARE-TIMI 58 clinical trial which showed a 26% reduction in hospitalisations for heart failure and cardiovascular death compared to standard treatment.

Analysts have previously suggested that vericiguat would need to show a 15-20% improvement on standard therapy to drive take-up in the market, and the results of VICTORIA – with most of the benefit coming from reduced hospitalisation and not cardiovascular death – could make it a niche product.

Bayer insists however that there is such an unmet need for new therapies in CHF that there is room for multiple different approaches, and it thinks there could be a role for vericiguat in some areas poorly addressed by other drugs such as post-event patients or in patients with worsening heart failure.

Bayer and MSD are also conducting a phase 2 trial (VITALITY) of vericiguat in HFpEF, with results due later this year.

The drug hasn’t yet been filed for approval in the US. When it comes to sales forecasts analysts are cautious, suggesting it is likely to remain a small player. Cowen have predicted sales of up to $500m by the middle of the decade, for example.