Novartis AG's Phase III Drug for Heart Failure Bombs Trial

March 22, 2017 (Last Updated: 5:05pm PT)
By Mark Terry, BioSpace.com Breaking News Staff

Basel, Switzerland – Novartis announced today that its Phase III RELAX-AHF-2 clinical trial of RLX030 (serelaxin) in patients with acute heart failure (AHF) failed to meet its primary endpoints.

Its primary endpoint was reduction of cardiovascular death through Day 180 or reduced worsening heart failure through Day five. The drug is a relaxin receptor agonist, a recombinant version of a naturally-occurring hormone, relaxin-2.

“We are disappointed this study did not confirm the efficacy of RLX030 in acute heart failure, especially given the urgent need for effective new treatments for this condition,” said Vas Narasimhan, Novartis’ global head, Drug Development, and chief medical officer, in a statement. “We will continue to further analyze the data to better understand and learn from these results as well as evaluate next steps for the overall program.”

Reuters noted that “Serelaxin had a troubled trial history, having already failed in 2014 to win the approval of European and U.S. regulators. Novartis pressed on in the hope of eventually gathering enough evidence to change regulators’ minds, but Wednesday’s announcement that the drug failed dashes those aims.”

The European Union regulators also had doubts about the drug’s efficacy and expressed concerns over the previous trial’s structure.

The drug was viewed as a way for Novartis to bridge the gap left by the expiration date of Diovan, another cardiac drug, which lost U.S. patent protection in 2012.

Tim Race, analyst with Deutsche Bank, wrote in a note to investors, “The failure of serelaxin will refocus the importance of Entresto to meet consensus long-term sales expectations as well as the importance for management to bolster its pipeline.”

Seamus Fernandez, an analyst with Leerink, wrote in a note to investors, “Given the post-hoc nature of the previous analyses, relatively small number of clinical events, and lack of historical success for other agents in large acute HF trials, we had previously been cautious on the chances for a favorable benefit on mortality outcomes. According to previous discussions with MEDACorp KOLs, success in this trial would have created a strong ethical mandate for use; however, we believe the failure essentially terminates all enthusiasm for the drug.”

Which puts pressure on Novartis for Entresto to success. But the drug has been slow to enter the market. In 2016, Entresto pulled in $170 million, even though Novartis has doubled down on pay-for-performance contracts and what John Carroll, writing for Endpoints News, says was “a relentless effort to build the data and payer deals needed to make the drug a success. Payers, though, have their own ideas on how to handle a drug like this. They erected barriers with high co-pays and prior authorization demands that made the drug hard to get.”

Two other of the company’s drugs, Diovan, a cardiovascular drug, and Gleevec, a cancer drug, have dropped in sales recently as well. At their peak, the two drugs had a combined sales of $8.2 billion, but in 2016 brought in only $4.4 billion.

Carroll notes that this failure, as well as those found by Amgen and Regeneron /Sanofi for their PCSK9 drugs in getting reimbursement in the cardiovascular field, underline the difficult of bringing new drugs to this market. “That kind of resistance will make it increasingly hard,” he writes, “for large players to tackle the big and expensive late-stage efforts that are needed to get these drugs across the finish line. Serelaxin may ultimately exercise exactly the opposite kind of influence that Novartis was looking for.”