Bayer faces an uphill fight with finerenone
Pivotal data on finerenone might see it approved, but competing in the market will be trickier.
Good, but perhaps not good enough. Such is the conclusion from the Fidelio-DKD trial of Bayer’s finerenone in diabetic kidney disease: the mineralocorticoid receptor antagonist hit its primary endpoint and demonstrated kidney-related and cardiovascular benefits – but the effect size lagged that seen with both Invokana and Farxiga.
Arguably the trial is a victim of its timing: SGLT2s became widespread as it was running, and this new class has set a very high bar for finerenone to beat.
The trials of finerenone, Invokana and Farxiga all have subtly different composite endpoints, making the always ticklish problem of comparing data from separate trials harder still. But with hazard ratios markedly better with the SGLT2s it is hard to escape the conclusion that finerenone is somewhat feeble.
And, on those endpoints that were the same in all three trials, Bayer’s project fell behind its rivals. The risk of death, for instance, was reduced by 10% versus placebo, compared with 17% and 30% for Johnson & Johnson and Astrazeneca’s products respectively.
|Cross-trial comparison of selected endpoints|
|Finerenone (Fidelio-DKD)||Invokana (Credence)||Farxiga (Dapa-CKD)|
|PCE: ESRD, sustained decrease of ≥40% in eGFR and renal death||0.82 (0.73–0.93)|
|PCE: ESRD, doubling of serum creatinine level, renal and CV death||0.70 (0.59–0.82)|
|PCE: ESRD, sustained decrease of ≥50% in eGFR, renal and CV death||0.64 (0.52–0.79)|
|ESRD||0.86 (0.67–1.10)||0.68 (0.54–0.86)||0.64 (0.50–0.82)*|
|CV death||0.86 (0.68–1.08)||0.78 (0.61–1.00)||0.81 (0.58–1.12)*|
|All-cause death||0.90 (0.75–1.07)||0.83 (0.68–1.02)||0.69 (0.53–0.88)*|
|*Also includes non-diabetic patients. PCE=primary composite endpoint. ESRD=end-stage renal disease. eGFR=estimated glomerular filtration rate. Source: NEJM.|
The Fidelio investigators proffered an assortment of possible explanations, noting differences in the patient populations as well as in the composite endpoints, and making the possibly rather obvious point that “mechanisms of action differ between drug classes”.
They added that Fidelio allowed SGLT2 inhibitor treatment, whereas the Credence trial of Invokana excluded patients treated with mineralocorticoid receptor antagonists. But less than 5% of the patients were on an SGLT2, and with numbers as small as these it is all but impossible to draw any robust conclusions about a possible additive effect – even if analysis of this subgroup was pre-specified, which is not clear.
The low rate usage of SGLT2s reflects the duration of Fidelio-DKD. The study was started in 2015, before this class became established in diabetes. The option exists for Bayer to run another trial with patents taking finerenone on top of SGLT2 therapy; certainly this would be one way to carve out a place in the market for the project.
But the risk is that Bayer could spend huge sums to reveal what might be a marginal additive effect. Finerenone’s phase II programme has already been protracted and expensive, with a second trial in diabetic nephropathy, Figaro-DKD, to report next year. And it could be tough to get another large study started and finished while the molecule still retains sufficient patent protection.
It is clear that the financial markets do not ascribe great value to finerenone: sellside consensus compiled by EvaluatePharma forecasts 2026 sales of $533m. Bayer might have to decide whether to cut its losses.