Boehringer Ingelheim and Eli Lilly’s collaborative effort to secure Jardiance’s (empagliflozin’s) place in the heart failure (HF) landscape has reached its first stumbling block.
The drug failed to show statistical significance in the Phase III EMPERIAL trials looking at the functional capacity of Jardiance in both HF with reduced ejection fraction (HF-REF) and preserved ejection fraction (HF-PEF) in patients with and without diabetes. This trial failure places doubt on the success of Jardiance in further trials for HF-REF and HF-PEF, and may impact the uptake of the drug when it reaches the market for HF.
The EMPERIAL trials took place following the results of the Phase III EMPA-REG OUTCOME trial which demonstrated the benefit of Jardiance compared to placebo by reducing cardiovascular (CV) death by 38%. The expectation of both EMPERIAL-reduced and EMPERIAL-preserved was to show that Jardiance was superior to placebo in improving exercise capacity and HF symptoms in patients with and without diabetes; however, although showing mortality benefit, there were neutral or inconsistent results surrounding exercise capacity and patient-reported outcomes.
The trial’s primary endpoint was centered on a six-minute walk test that would determine the change in exercise capacity of the patient from baseline to 12 weeks. The success of the drug in trials would have proven the symptomatic and quality of life improvement with the drug, but its failure adds speculation on the expected class effect of sodium-glucose co-transporter (SGLT) inhibitors and moves the focus onto the successful trial results of Farxiga (dapagliflozin), AstraZeneca’s impressive contender for the treatment of HF-REF and HF-PEF in both diabetics and non-diabetics.
Although Jardiance is still undergoing the EMPEROR-preserved and EMPEROR-reduced trials, which look at the drug reducing hospitalization risk and mortality, GlobalData believes that the EMPERIAL trial results will benefit Farxiga as prescribers will now see it as the superior of the two, which may not have been the case prior to these trial results. Boehringer Ingelheim and Lilly also have the added difficulty that Farxiga is set to be launched in advance of Jardiance for HF-REF, which will capture a large patient share from its head start as KOLs have vocalized the need for a treatment option with mortality and hospitalization benefit.
GlobalData expects the upcoming results of the EMPEROR trials in 2020 to cause a make-or-break standpoint for Jardiance, as if it cannot prove benefit in non-diabetics, Farxiga will have a significant market advantage. Furthermore, Jardiance will now likely face greater competition from Novartis’ Entresto. Until now, Jardiance’s main competition was seen to be Farxiga; however, if Jardiance cannot prove a substantial benefit to match that of Farxiga, the issues of polypharmacy may reduce its uptake even further. Prescribers may prefer to use a replacement therapy such as Entresto rather than Jardiance as an add-on therapy, especially if the EMPEROR trial results do not show significant benefit compared to that shown by results from Entresto’s clinical trials.
Results of the EMPERIAL trials are expected to be discussed in 2020.
GlobalData (2019). Heart Failure – Global Drug Forecast and Market Analysis to 2028, to be published