Novartis Overhyping Heart Drug Study Results?

Novartis Overhyping Heart Drug Study Results?

November 9th, 2012 // 1:49 pm @

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Trying to put a good face on a less-than-ideal situation is human nature. And drugmakers are human, too – or at least collections of humans. So it is not surprising that the language used in a press release announcing results of an important study for a potentially big-selling treatment might overstate the case a wee bit.

However, a press release issued yesterday by Novartis (NVS) to trumpet the results of its RELAX-AHF study, a Phase III trial that examined the use of its serelaxin drug for treating acute heart failure, was a not-very transparent attempt to spin decidedly mixed results (read here). The lead investigators, in fact, were more circumspect in the pages of The Lancet, where the results were published, along with an accompanying editorial from another researcher.

Specifically, the headline on the press release boasts that “RLX030 improved symptoms and reduced deaths by one-third in patients with acute heart failure.” Good news, yes? This is the sort of finding that can excite investors and underscore sales estimates. But some Wall Street analysts were quick to note that Novartis was glowing without sufficient reason.

In The Lancet, meanwhile, the lead investigators describe the results as a “mild” improvement” and the editorial suggests that the clinical relevance of the findings are “obscure.” The study failed to show the drug kept patients alive or out of a hospital longer than a standard treatment.

Consequently, Leerink Swann analyst Seamus Fernandez wrote in an investor note that “despite encouraging headline data… (The Lancet editorial and his own consultant) questioned the reliability and robustness of the effect on total mortality in the context of a mixed symptomatic benefit and no effect on secondary endpoints, which included hospitalizations.”

Similarly, Sanford Bernstein analyst Tim Anderson called out Novartis on its tactic. “The press release… reads unabashedly positive, but in fact the data were mixed, and certainly weaker than what results of an earlier Phase 2 trial showed,” he wrote in an investor note. “At first blush, this may seem impressive, yet this was neither a primary nor a secondary endpoint and in fact was a safety endpoint, the statistical powering of which is questionable.

“In a more balanced way, in their Lancet article the lead investigators say that this finding may only be a play of chance given the fact that it is not consistent with the key secondary endpoints of the trial, all of which missed statistical significance. The writer of the Lancet editorial calls the mortality finding ‘hypothesis generating.’ It would have been much more important if a mortality benefit had been demonstrated on the official secondary endpoint that evaluated this at the 60-day mark – this was not the case.”

The editorial, by the way, was written by Marvin Konstam of the CardioVascular Center at Tufts Medical Center and Tufts University School of Medicine, and he noted the investigators should be applauded for “restraining their zeal in interpreting the favorable mortality trends,” given the small number of events. At the same time, Konstam acknowledges that the lead investigators are justified in calling the results positive, despite significance in only one of two endpoints.

For this reason, Anderson suggests that anyone interested in the results should read The Lancet for a more sobering view. The primary endpoint measured reduction in shortness of breath two different ways, but only one met statistical significance. And Anderson points out the 19 percent relative reduction was much lower than the 53 percent figure in a Phase II trial.

This is not to suggest the drug cannot or will not be approved, even based on the existing data, if only because there is a pressing need for therapies for heart failure. Even if the drug were approved, writes Fernandez, “the real commercial upside opportunity is tied more to a confirmed benefit on either cardiovascular or total mortality, which would require a larger Phase III study to prove the longer-term benefits… for the treatment of AHF.”


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