Firibastat – First-in-class – heart failure

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Firibastat for the prevention and treatment of congestive heart failure

Despite some medical breakthroughs, mortality rate due to heart failure remains high: about 50% of the persons diagnosed with heart failure die within 5 years. There is therefore an urgent need to develop new pharmacological treatments for heart failure. Quantum Genomics intends to demonstrate the therapeutic benefit of BAPAIs for the treatment of heart failure.

Exploratory works carried out by the team led by Dr. Catherine Llorens-Cortès in collaboration with the team of Pr. F. Leenen at the Heart Institute of Ottawa (Canada) have demonstrated that an hyperactivity of the brain renin-angiotensin system as well as that of the sympathetic system could contribute to the progressive remodeling and dysfunction of the heart after a myocardial infarction. When administered to rats which have undergone myocardial infarction, firibastat was found to inhibit APA and the production of AngIII at the level of the brain, to reduce the activity of the sympathetic nervous system and thus to improve the the cardiac left ventricle function of the animals.

The firibastat appears as a new promising therapeutic agent for the treatment of heart failure both in Human and animals.

After collecting excellent data on animal efficacy and human safety in the Phase IIa study, Quantum Genomics announced the design of its Phase IIb study in heart failure last June 2018 with its first-in-class drug candidate, firibastat.

The aim of this study named QUORUM (QUantum Genomics firibastat Or Ramipril after acUte Myocardial infarction to prevent left ventricular dysfunction) will be to assess the efficacy and the safety of firibastat compared to ramipril after acute myocardial infarction (AMI). Firibastat targets the brain renin-angiotensin system. Through a triple mechanism of action, firibastat makes it possible to produce a simultaneous effect on the arteries, heart and kidney, offering promising perspectives in the treatment of heart failure (HF).

QUORUM will be a multicenter, multinational, randomized, double-blind, active-controlled trial with 3 parallel groups. The study will enroll approximately 300 subjects, after MI, treated with primary percutaneous coronary intervention (PCI) and with reduced left ventricular ejection fraction (LVEF). Study subjects will be randomized to receive either low dose of firibastat, standard dose of firibastat or ramipril for 3 months.

The primary endpoint will be the change from baseline in LVEF assessed by cardiac magnetic resonance (CMR) after a 3-month treatment. Other endpoints will include cardiac events, functional status, safety and change in HF biomarkers.

The CRO (Contract Research Organization) Premier Research was selected to conduct the study. The selection of centers is in progress and regulatory filings have been made.

The results of the QUORUM trial have been presented during the ESC congress (European Society of Cardiology) by the Principal Investigaron, Professor Gilles Montalescot. The study has pointed out that the effectiveness of firibastat on the entire study population is of the same level as of the most effective molecule in post mycardial infarction to date, ramipril. In severe patients with an ejection fraction less than 50%, firibastat appears to be more effective than  ramipril. On the other hand, QUORUM shows that firibastat improves the blood pressure profile. Substantial reduction of blood pressure with ACE inhibitors such as ramipril, the reference treatment, is a  limiting factor of current management of severe patients. For this reason, QUORUM’s phase IIb results pave the way for a phase III clinical study in severe patients whose protocol will be finalized with a selected partner pharmaceutical company.