Drug (Brand / Generic)
Inspra / Eplerenone
Company / Licensee
Chronic heart failure
Mineralcorticoid Receptor (MR)
Approved in US, EU, Netherlands and Japan
Inspra (eplerenone) is indicated for the treatment of chronic heart failure. It was developed by Pharmacia Corporation, which was acquired by Pfizer in 2002.
The drug was approved by the US Food and Drug Administration (FDA) in 2002. It also received approval for use in reducing the risk of cardiovascular (CV) mortality in the EU and the Netherlands, and has been approved in Japan for treating hypertension.
Chronic heart failure
Chronic heart failure occurs when the heart is unable to pump enough oxygen rich blood supply to the body. Heart failure also occurs due to diseases that stiffen or weaken heart muscles and diseases that demand oxygen-rich blood beyond the capacity of the heart.
In developed countries about 2% of the adults suffer from chronic heart failure, increasing to 6% to 10% in those above 65 years old. The costs associated with treating chronic heart failure are estimated to be more than $35bn in the US alone.
Inspra mineralcorticoid receptor
Inspra is a mineralcorticoid receptor (MR) antagonist with a high degree of selectivity. The drug contains 50mg or 25mg of eplerenone and can be administered orally. It also contains some inactive ingredients such as polysorbate 80, yellow and red iron oxides, lactose, titanium dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, talc and lauryl sulfate.
The drug blocks the actions of the aldosterone hormone, which plays a vital role in increasing blood volume and regulating blood pressure.
In July 2010, Pfizer initiated Phase III clinical trials on Inspra in Japan. The study has enrolled 220 Japanese chronic systolic heart failure patients. It is scheduled to be complete by August 2014.
The purpose of the study is to compare the efficacy and safety of the drug with a placebo. The primary outcome measure is to find the first occurrence of CV mortality or heart failure hospitalisation. The secondary outcome measures include finding all-cause mortality, CV mortality and all-cause hospitalisation.
The company has launched Phase IIIb clinical trials on the drug across 272 study locations in 29 countries. Named EMPHASIS-HF, the study was initiated in March 2006 and completed in May 2011.The primary objective was to evaluate the safety and efficacy of Inspra in comparison with a placebo. It was a multinational, randomised, double-blind, placebo-controlled and parallel-group trial. The study enrolled 2,737 participants with NYHA (New York Heart Association) Class II chronic systolic heart failure with mild symptoms. Recruitment to the EMPHASIS-HF trial was halted in May 2010 after the pre-specified analysis showed that the drug had met the primary endpoint compared with a placebo.
The primary results of the EMPHASIS-HF study were unveiled in November 2010. The results showed that the Inspra-administered group of patients experienced a significant 37% relative risk reduction compared with the placebo group. The study also revealed that the drug was effective in bringing a 24% reduction in CV mortality, a 23% reduction in all-cause hospitalisation, a 24% reduction in all-cause mortality and a 42% reduction in HF hospitalisation.
It was also observed that the incidence of hyperkalemia (elevated potassium) among the Inspra-administered group was 11.8%, while was 7.2% in the placebo group. In the case of hyperkalemia (low potassium) the incidence was 7.5% in the Inspra-administered group and 11.0% in the placebo group.
Final results of the EMPHASIS-HF study were announced in May 2011. The results showed that Inspra plus standard therapy significantly reduced the occurrence of new onset atrial fibrillation in patients with systolic heart failure compared to the placebo group.