Bayer and Merck & Co have unveiled the data from their phase 3 trial of vericiguat in high-risk heart failure, backing up a top-line message from the study reported last November.
The results of the 5,050-patient VICTORIA study – the first pivotal trial of the oral soluble guanylate cyclase (sGC) stimulator – reveal a 10% reduction in the rate of cardiovascular deaths and hospitalisations among patients with worsening heart failure and reduced ejection fraction (HFrEF) compared to placebo.
sGC stimulators are thought to work by correcting a dysfunctional nitric oxide signalling pathway seen in heart failure.
After almost 11 months’ follow-up, 35.5% of the vericiguat group and 38.5% of the placebo group hit the primary endpoint, with most of the benefit coming from a reduction in hospitalisations for heart failure. The difference in cardiovascular death and all-cause mortality between the groups wasn’t significantly different.
Overall, the difference between vericiguat and placebo translated to an absolute reduction of 4.2 events per 100 patient-years, in other words that treating 24 to 28 people with vericiguat for one year would prevent one cardiovascular-related death or hospital admission.
The data were presented at the American College of Cardiology (ACC) conference – taking place for the first remotely because of the coronavirus pandemic – and also published in the New England Journal of Medicine.
The patients in the trial were well treated, with more than a third having a pacemaker or implantable cardioverter defibrillator (ICD), and 90% on two or three standard heart failure drugs, but were very sick, with a high event rate in the trial.
That makes the improvement seen with vericiguat impressive, according to lead investigator Paul Armstrong of the University of Alberta in Canada.
“For a group of patients with this form of high-risk heart failure, where other heart failure drugs have rarely been studied, vericiguat provides a significant novel addition to usual treatment,” he said.
Some outstanding questions include where vericiguat lies in relation to the SGLT2 inhibitors such as Boehringer Ingelheim/Eli Lilly’s Jardiance (empagliflozin) and AstraZeneca’s Farxiga/Forxiga (dapagliflozin), which are also improving outcomes when added to standard therapy in HFrEF, added Armstrong.
On the face of it, Farxiga’s 26 improvement in cardiovascular death and worsening heart failure compared to placebo in the DAPA-HF trial seems a stronger effect, but there’s the usual caveat of comparing different studies, and it’s worth noting AZ’s drug was tested in a less sick patient population.
Moreover, having multiple new therapeutic options will be good for patients and cardiologists, particularly as drugs often end up being used in combination in heart failure.
Overall, the data suggests Merck and Bayer’s decision to move vericiguat into a phase 3 programme after mixed results in the phase 2 SOCRATES-REDUCED trial was a gamble worth taking.
Another new drug for heart failure – Novartis’ Entresto (sacubitril/valsartan) – reached blockbuster sales levels in 2018 after a slow start following its launch in 2015, but with sales rocketing to $1.7bn last year the potential for new drugs in this big patient population is clear.
Bayer and Merck are now planning additional studies in heart before they file for approval of vericiguat – which if approved would be the first drug in the sGC stimulator class – in HFrEF.
The latest results are however also raising expectations that vericiguat could hit the mark in an ongoing phase 2 trial called VITALITY in heart failure with preserved ejection fraction (HFpEF), a form of heart failure that accounts for around half of all cases and currently has no approved drug therapies.
Bayer and Merck are also conducting a phase 2 trial of vericiguat in HFpEF which was scheduled for completion by the end of last year and should be at the data crunching phase. Here too the SGLT2 inhibitor drugs are circling.
Farxiga is currently being studied in HFpEF in the DELIVER trial as well as the DETERMINE study, which is enrolling both HFrEF and HFpEF patients, with results due later this year, while Jardiance is being put through its paces in this setting in the EMPEROR-Preserved study.