Swiss drug giant Novartis has cuts its 2007 turnover forecast after sales of its irritable bowel syndrome drug Zelnorm were suspended following fears raised by US regulators that the treatment could be linked to heart attacks and strokes.
The US Food and Drug Administration asked Novartis to suspend US marketing of Zelnorm (tegaserod), known as Zelmac in Switzerland, Latin America and the Asia-Pacific region, after the firm notified the agency about a retrospective analysis of data from more than 18,000 patients on its clinical trial database. The data showed that events occurred in 13 out of 11,614 patients treated with Zelnorm, compared to one case in 7,031 placebo-treated patients and all the patients affected had pre-existing cardiovascular disease and/or risk factors.
James Shannon, head of development at Novartis Pharma, said that although the company has complied with the FDA's request and is collaborating with the agency, “we continue to believe that Zelnorm provides important benefits for appropriate patients." Novartis also noted that the rate of cardiovascular ischemic events seen in Zelnorm-treated patients in controlled trials “corresponds approximately with the expected rates for such events in the general population,” adding that “a small (but not statistically significant) imbalance in cases of angina pectoris” was included in the US label when the drug was approved in 2002.
Causal relationship 'unlikely'
The firm also quoted Jeffrey Anderson, Professor of Internal Medicine at the University of Utah, an independent cardiologist who reviewed the data, who said that “a causal relationship is unlikely between tegaserod and the rare cardiovascular ischemic events observed in clinical trial," while the data “did not show any consistent pattern of event type, time to event or dose relationship in tegaserod-treated patients."
Nevertheless, the FDA is taking no chances and Douglas Throckmorton, deputy director for the Center for Drug Evaluation and Research, said that “here, a potential risk of very serious harm to patients who have this non-life-threatening condition was recently identified, making this action necessary." The agency added that it will work with Novartis to allow access to Zelnorm as an investigational drug for patients with no other treatment options and may consider limited re-introduction of the treatment at a later date “if a population of patients can be identified in which the benefits of the drug outweigh the risks.” However any such proposal would be the subject of a public advisory committee meeting before any decision could be made, the agency added.
The suspension is a big blow for Novartis as Zelnorm sales in 2006 rose 34% to $561 million, with $488 million coming from the USA and now the firm has revised its financial targets for 2007. Group sales are now expected to be above 5%, and for the pharmaceuticals division to reach “a low to mid-single-digit rate.” A previous forecast had estimated that group turnover would rise at a mid- to high-single-digit percentage rate and Novartis added that it is still evaluating the impact the suspension will have on earnings.
Analysts were slightly taken aback by the Zelnorm withdrawal but are not predicting any long-term damage as yet, although that could change once the risk of product liability lawsuits is evaluated. However the case highlights the problem in finding safe and effective IBS treatments and the likelihood of a European launch for Zelnorm all but vanished a year ago after the EU's Committee for Medicinal Products for Human Use rejected the application for a second time. GlaxoSmithKline may have re-launched Lotronex (alosetron) in the USA in 2002 but under a restricted use label, after it had been withdrawn two years earlier following a small number of fatalities amongst patients who developed serious gastrointestinal events while taking the drug.