ESC 2020 – Jardiance joins Farxiga in showing heart failure benefit

A similar benefit suggests a class effect with the SGLT2s in heart failure, leaving Lilly and Boehringer playing catch-up to Astra.

Conferences

A year ago Astrazeneca reported impressive data with its diabetes drug Farxiga in heart failure patients both with and without diabetes. At this year’s European Society of Cardiology meeting Lilly and Boehringer Ingelheim have shown an almost identical effect with their rival SGLT2 inhibitor, Jardiance.

True, the Emperor-Reduced study of Jardiance enrolled a sicker patient population than the Dapa-HF trial of Farxiga, but the heart failure benefit is now starting to look like a class effect of the SGLT2s. Jardiance’s makers will now want to regain ground on Astra, which saw Farxiga approved for heart failure with reduced ejection fraction in May.

However, Astra has not had long to make its mark, and cardiologists are notoriously conservative. Perhaps Jardiance will not suffer too much from being a fast follower.

Royal rumble

Based on the evidence so far there is not much to differentiate the two agents.

Emperor-Reduced showed a 25% reduction in the composite primary endpoint, cardiovascular death or hospitalisation, with Jardiance versus placebo. The findings were also published in the New England Journal of Medicine.

This is almost a carbon copy of the result reported from Dapa-HF last year (ESC 2019 – Farxiga looks DAPA outside diabetes, September 1, 2019).

Cross-trial comparison of Farxiga vs Jardiance in HFrEF
Product Trial name Trial ID Primary endpoint Risk reduction p value
Farxiga DAPA-HF NCT03036124 CV death or worsening of HF (hospitalisation for HF or urgent HF visit) 26% p=0.00001
Jardiance Emperor-Reduced NCT03057977 CV death or hospitalisation 25% p<0.001
Source: ESC presentations.

However, differences in the trial populations could come into play. Both studies enrolled patients with an ejection fraction of 40% or less, but the Emperor-Reduced authors noted that their study included more patients with a markedly reduced ejection fraction, of 30% or less.

Demonstrating that the Emperor-Reduced population was more severe, the incidence of the primary outcome was around 40% higher versus Dapa-HF, the investigators added.

Driven by hospitalisations

Notwithstanding this, there are plenty of parallels between the trials. In both studies the overall benefit was driven by an impact on hospitalisations rather than cardiovascular death.

However, this was more marked in Emperor-Reduced, where the risk of hospitalisation was 31% lower with Jardiance versus placebo, and the risk of CV death was reduced by just 8%.

In contrast, Dapa-HF found an 18% reduction in the risk of CV death, and a 30% reduction in the risk of worsening HF, with Farxiga.

Both trials showed a similar benefit in diabetics and non-diabetics. In Emperor-Reduced diabetics saw a 28% reduction in the risk of the primary endpoint, and non-diabetics a 22% reduction. Around half of the patients in Emperor-Reduced were diabetic, a similar proportion to that seen in Dapa-HF.

Safety looked clean in both trials. Reassuringly, there was no increase in the number of lower limb amputations with Jardiance in Emperor-Reduced; this side effect has been closely watched with since being linked with Johnson & Johnson’s SGLT2 Invokana.

Convincing cardiologists

A spokesperson for Boehringer told Vantage that Jardiance might be filed in HF by the end of this year. But it looks like the biggest difficulty now will not be getting Jardiance approved in HF, but convincing cardiologists to use the drug.

The lead investigator of Emperor-Reduced, Dr Milton Packer of Baylor University, alluded to this during an ESC press conference on Friday, saying hundreds of thousands of HF patients could benefit from SGLT2s, “but it depends on whether physicians are paying attention”.

He said many doctors treating HF were “still using what was state of the art 15 years ago”. But he added that the SGLT2s should now become standard of care in HF with reduced ejection fraction, alongside drugs like beta-blockers.

A spokesperson for Astra told Vantage that it was too soon to comment on Farxiga’s sales in HF, but presumably there will soon be some clues about the drug’s uptake in the new indication.

At a press event on Friday Astra’s head of biopharmaceuticals R&D, Sir Mene Pangalos, played down the prospect of a big battle between Farxiga and Jardiance, saying that the company “first and foremost” wants to grow the SGLT2 class as a whole.

It might take a while for the tide to turn, but the evidence for more widespread use is mounting.

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