Novartis' Irritable Blockbuster Syndrome

Novartis has a Zelnorm problem.

Not anymore

The Swiss drugmaker suspended sales of the IBS drug on Friday at the behest of the FDA, which wants an advisory committee to weigh in on the significance of a safety signal unearthed in an 18,000 patient retrospective analysis of trial data. Novartis sold $561 million worth of the drug in 2006.

The data suggested Zelnorm patients were more likely to experience an ischemic cardiovascular event than placebo patients (one in one thousand for the Zelnorm group, one in ten thousand for the placebo group), though Novartis has noted that the rate in the treatment group more closely hews to the rate in the general population and each of the effected patients had other risk factors for such events.

Analysts have removed Zelnorm sales from their models, for now, awaiting FDA's decision.

IBS has been notoriously tricky for pharma, though the massive potential market size has meant no shortage of compounds in development. Only Nelnorm and GSK's Lotronex have made it to market in the indication, neither has been particularly successful, each has serious GI side effects, and now each has been pulled from the market--albeit temporarily. Lotronex was yanked in 2000, nine months after launch, and returned to a much narrower market by popular demand in 2002 with a black box warning.

Zelnorm's suspension is potentially temporary--which would mean less of a liability headache for Novartis even if sales never recover. Lotronex's did not--though the safety concerns for the two drugs are very different.

(Graphic from "Building a Business in Drug Safety," Jan. 2006, The RPM Report)

But sources close to Novartis note that the company had originally asked FDA not to simply pull the drug—but to contraindicate its use, with a black-box warning, for at-risk popualtions: older women and those with cardiovascular risk factors. The drug still should be available, Novartis argued, for younger women (roughly 40% of its users, who usually get severe constipation during menstruation).

FDA said no. Until the situation is more clearly understood, there was no reason to run the risk: IBS isn’t a fatal disease; there are—inadequate—alternatives; better safe than sorry, said the Agency.

Novartis was in no position to disagree. But it must be feeling picked on: the Zelnorm suspension is its second bit of bad regulatory news in weeks. Even worse: FDA’s “not yet” on Novartis’ most important pipeline drug, Galvus, back in January – while giving Merck’s competitive Januvia and Janumet the all clear – and what is likely an insuperable competitive lead.