BASEL, Switzerland—Novartis announced today it will submit a revised filing package, including new data analyses, for re-examination for conditional approval of RLX030 (serelaxin) for acute heart failure (AHF) by the Committee for Medicinal Products for Human Use (CHMP) following a negative opinion issued today. In accordance with the CHMP process a revised opinion could be granted as early as the second quarter.
"With the results from RELAX-AHF showing significant mortality benefits with RLX030 in patients with AHF and recognizing 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."
Regulatory approval is continuing under review by the U.S. Food and Drug Administration (FDA) where RLX030 was granted Breakthrough Therapy designation status in June 2013. Reviews are also underway with health authorities in 16 additional countries, Novartis reports. On February 13th Novartis is scheduled to present RLX030 efficacy and safety data at the FDA's Cardiovascular and Renal Drugs Advisory Committee meeting to discuss potential US approval
In September 2013, results from a new analysis of the Phase 3 RELAX-AHF study published in the European Heart Journal and presented at the European Society of Cardiology (ESC) congress in Amsterdam indicated that RLX030 consistently improved symptoms and mortality across multiple subgroups of patients with acute heart failure assessed in the trial
The addition of RLX030 to conventional treatment led to improvements in breathlessness (dyspnea) and mortality at six months across all pre-specified subgroups including those with renal impairment (eGFR<50ml/min), the elderly (>=75 years) and patients with atrial fibrillation, although at that time it was noted that the small numbers of patients in each group limited the statistical conclusions that could be drawn. AHF patients require urgent treatment so prompt decision-making to stop heart failure worsening is crucial in spite of patients often having diverse clinical profiles.
"Treatment of AHF is largely unchanged since the 1970s and with RLX030 Novartis aims to bring the first therapy shown to improve longer-term outcomes to patients," Epstein said at the time. "This new analysis adds to the overall results from RELAX-AHF that showed intervention with RLX030 is key to halting the downward spiral of organ damage that occurs during an AHF episode."
Each year around 3.5 million AHF episodes happen in the US and EU alone; this is expected to increase further as the population ages. Every AHF episode contributes to a downward spiral of worsening heart failure and damage to vital organs, such as the heart and kidneys, which decreases the chance of the patient surviving another episode. There is an urgent need for new treatments that help relieve patients' symptoms and protect vital organs against damage during an AHF episode, as well as have the potential to increase life expectancy in the AHF patient population.
In June 2013 Novartis announced that the FDA had granted Breakthrough Therapy designation status to RLX030. The agency concluded that RLX030 qualifies for a Breakthrough Therapy designation after considering the available clinical evidence which supports a substantial improvement over currently available therapies for AHF, a life-threatening illness.
The FDA's decision was supported by efficacy and safety results from the phase 3 RELAX-AHF trial, which also showed that patients who received RLX030 had a 37 percent reduction in mortality at six months after an acute heart failure episode compared to those who received conventional treatment
RLX030 (serelaxin) is a form of a naturally occurring hormone (human relaxin-2), present in both men and women, although its levels rise in pregnant women to help the body cope with the additional cardiovascular demands during pregnancy. RLX030 is proposed for administration on admission to the emergency room to patients experiencing an AHF episode and is infused over a 48-hour period, in addition to conventional therapies.
In RELAX-AHF, RLX030 was shown to have both short and longer-term effects, helping patients breathe during and after an AHF episode, reducing the rate of heart failure worsening. Data from the clinical trial program has also shown that RLX030's side effects are comparable to conventional therapy and it was generally well tolerated.
Another Novartis compound called LCZ696, an angiotensin receptor neprilysin inhibitor, is the first in a new class of dual-acting drugs being evaluated for the treatment of chronic heart failure. A robust clinical development program, including two global phase 3 studies, is underway to fully assess the efficacy and safety profile of LCZ696.