Bayer has started three late-stage trials of its heart failure candidate finerenone after reporting encouraging phase IIb data at the European Society of Cardiology (ESC) meeting in London.
The decision to push the mineralocorticoid receptor antagonist (MRA) into phase III trials comes on the back of the ARTS-HF study in patients with diabetes or chronic kidney disease (CKD) who also have worsening heart failure.
The results suggested finerenone (BAY 94-8862) was as effective as an older MRA called eplerenone but was less prone to cause high potassium levels in the blood (hyperkalaemia), which can increase the risk of arrhythmias and sudden cardiac death. Hyperkalaemia often occurs in advanced heart failure patients and is exacerbated by diabetes and kidney disease.
Eplerenone and another MRA called spironolactone are recommended treatments for heart failure but their use is discouraged by the need for close monitoring of serum potassium levels as well as other side effects such as worsening kidney function and hormonal changes.
Despite being recommended in treatment guidelines, only about 32% of eligible patients in the US actually receive MRAs, according to a 2011 study reported in the American Journal of Cardiology.
In ARTS-HF, Bayer’s drug was equivalent to eplerenone in reducing a marker of heart failure (NT-PproBNP) as well as “meaningful reductions” in secondary measures such as the rate of all-cause death and cardiovascular hospitalisations. There were also signs it may have a better side-effect profile.
Bayer has previously indicated that its decision to advance finerenone into phase III would hinge on the outcome of ARTS-HF
Presenting the data at the ESC, Gerasimos Filippatos of Athens University Hospital Attikon in Greece noted that at the optimal dose of 10mg/20mg there was a 44% reduction in cardiovascular events and mortality, although he noted additional trials would be needed to explore that potential benefit further.
Bayer has announced that it will start a phase III study in more than 3,000 heart failure patients with reduced ejection fraction and type 2 diabetes and/or chronic kidney disease – FINESSE-HF – as a direct follow-on to the ARTS-HF trial.
“Despite recent advances, chronic heart failure is still a deadly disease with five-year survival rates similar to those of patients with advanced cancer,” said the pharma company in a statement.
If approved, finerenone would compete with Novartis’ much-anticipated Entresto (sacubitril and valsartan), a potential blockbuster that was granted early approval by the FDA in July.
Meanwhile, it also plans to conduct two trials in patients with diabetic kidney disease (DKD), namely FIGARO-DKD and FIDELIO-DKD, that build on an earlier phase II trial which showed that adding finerenone to drugs such as ACE inhibitors or angiotensin II receptor antagonists seemed to reduce renal damage.
If successful in these trials, finerenone could become the first MRA to be approved for DKD.