Novartis maintained today it will stick to its development plans for the experimental drug serelaxin (RLX030), even after the FDA formally rejected the acute heart failure (AHF) treatment for reasons similar to those that accounted for the product’s three previous regulatory setbacks this year.
In a statement, Novartis said it received a Complete Response Letter from FDA in which the agency stated that further evidence on the efficacy of RLX030 is required before an approval can be granted.
Novartis said in response that it is continuing to expand the data supporting serelaxin’s efficacy by staying the course of its global clinical program—including the RELAX-AHF-2 trial which the company said will enroll more than 6,300 patients.
"In accordance with the FDA's advice we will continue to expedite our clinical trial program to build the supporting body of evidence,” Tim Wright, global head of development for Novartis Pharmaceuticals, said in a statement.
Novartis presented phase II and III efficacy and safety data, including from the 1,161-patient phase III RELAX-AHF study. The company has highlighted results from RELAX-AHF showing that patients who received serelaxin had a 37% reduction in mortality at six months after an AHF episode compared to those who received conventional treatment.
Since last year, Novartis has been recruiting patients for a follow-up Phase III study, RELAX-AHF-2, designed to replicate the first trial’s key findings in a different primary endpoint, cardiovascular mortality. Plans call for more than 6,300 patients will be assessed in the second study, of which approximately 1,000 will be from the U.S. The study is expected to generate results in 2016.
“We continue to believe RLX030 has the potential to be an important treatment for AHF and have been encouraged by feedback from FDA advisory committee members noting the data are intriguing."
However, the curiosity of members of FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) wasn’t enough to prevent the panel from voting 11–0 on March 27 to recommend that FDA reject serelaxin, which has the trade name Reasanz.
FDA typically abides by advisory recommendations such as those of CRDAC and staff reports. A staff report on serelaxin raised three concerns:
Novartis’ reliance on one clinical trial to assess serelaxin’s effect on dyspnea rather than at least two, or one trial with data for multiple studies.
The single trial assigned the worst reported score to patients who died or had worsening heart failure during the first 5 days. FDA questioned if the first trial’s primary endpoint would have been achieved if a different score had been assigned.
The trial focused on serelaxin’s beneficial effect on dyspnea, dismissed by FDA as an exploratory finding that did not address the AHF indication.
In its recommendation against serelaxin, the EMA’s Committee for Medicinal Products for Human Use (CHMP)—recommended against commission approval of serelaxin. CHMP said Novartis’ study results did not demonstrate a benefit for short-term relief of dyspnoea over up to 24 hours—and said the clinical relevance was unclear for serelaxin’s showing some benefit over five days.
FDA rejected serelaxin even though the drug carries the agency’s Breakthrough Therapy Designation.