Novartis to request conditional marketing authorisation in EU

The file for regulatory approval is continuing review by the Food and Drug Administration (FDA) in the US where RLX030 was granted Breakthrough Therapy designation status in June 2013.[2] Reviews are also underway with health authorities in 16 countries around the world.

“With the results from RELAX-AHF showing significant mortality  benefits  with RLX030 in patients with AHF and recognising that there had been no treatment breakthroughs in this area for 20 years, Novartis took a decision to file for regulatory approval,” said David Epstein, Division Head of Novartis Pharmaceuticals. “It has become apparent through the review process and in accordance with advice we’ve received that the current evidence package may be more compatible with an application for conditional approval in the EU. We look forward to providing a revised package for review to the CHMP shortly.”

In September 2013 the second phase III study RELAX-AHF-2 started recruitment of the over 6000 patients who are expected to be enrolled. The goal is to replicate the key findings of RELAX-AHF and the study will assess cardiovascular mortality as the primary endpoint. This would be one of the largest and most robust programs undertaken by a company for an AHF drug.

RLX030, a relaxin receptor agonist,[3] is a form of a naturally occurring hormone (human relaxin 2) present in both men and women which rises in women during pregnancy to help the body cope with the additional cardiovascular demands.[4,5] RLX030 is thought to have multiple effects including relaxing the blood vessels, reducing fluid buildup and protecting the heart and vital organs from the cascade of damage that occurs during an AHF episode.[3,6–9] More than 1.5 million AHF episodes happen every year in Europe alone,[10,11] with 1 in 5 patients not surviving a year afterwards.[12–17]

RLX030 was studied in the phase III RELAX-AHF trial, which showed it had both short and longer-term effects, relieving symptoms and reducing the rate of heart failure worsening.[1] In the trial patients who received RLX030 also had a 37% reduction in mortality at six months after an AHF episode compared to those who received conventional treatment.[1] Data from clinical trials has shown that RLX030 was generally well tolerated.[1,18]

Heart failure is a debilitating and potentially life-threatening condition where the heart cannot pump enough blood around the body. More than 15 million people suffer from heart failure globally and this number is increasing.[10,19] The condition is often fatal when patients have one or repeated acute heart failure episodes.[19] As an AHF episode approaches, patients become severely breathless and rapidly gain weight due to fluid build-up in the lungs and around the body. This is often compared to the sensation of drowning.[20]

Patients experiencing an AHF episode need to be rushed to the emergency room for urgent treatment, making AHF the most common cause of hospitalisation in patients over 65 years.[10,21] Currently 20 to 30% of patients die within 1 year after experiencing an AHF episode, and 3-4% do not survive the initial episode.[12–17] This means AHF causes more deaths than some advanced cancers, including breast and bowel cancer.[22]