April 5, 2010
Salix Pharmaceuticals Inc.'s path forward should become clear shortly with the approved antibiotic Xifaxan in its third potential, and much-coveted, indication: irritable bowel syndrome.
Abstracts related to Phase III trials are due for online viewing shortly, and the company will present full data at Digestive Disease Week in May. Top-line news confirmed in September that both studies, TARGET 1 and TARGET 2, met primary and secondary endpoints in IBS.
But opinions are split regarding how much market share Xifaxan can capture.
IBS comes in three forms: diarrhea-predominant, constipation-predominant, and mixed, in which the symptoms alternate. Today, no drug on the market can claim to relieve more than one of the subsets, and Xifaxan is going after diarrhea-predominant and mixed disease.
Doctors, though, may prove reluctant to prescribe an antibiotic for chronic IBS.
"I think [Xifaxan] will do OK, but it's not going to capture a huge market share," said Iva Holder, analyst with Decision Resources. She predicted sales of about $66 million by 2018, at which point the IBS market will total about $1.52 billion.
"Whatever use it's going to see will be more episodic and limited," Holder told BioWorld Today. Cleared by the FDA previously for traveler's diarrhea, Xifaxan (rifaximin) last month won the U.S. marketing go-ahead for reducing the risk of overt hepatic encephalopathy. (See BioWorld Today, March 26, 2010.)
London-based GlaxoSmithKline plc's Lotronex (alosetron) won the FDA's blessing in IBS for women (who make up 70 percent of the market) but was withdrawn from the market by GSK in 2000 after nine months of sales. Five Lotronex patients died, and the risks of ulcerative colitis and severe constipation dogged the 5-HT3 receptor antagonist. Lotronex eventually came back but with a restrictive label, and now belongs to the San Diego-based diagnostics/specialty firm Prometheus Laboratories Inc.
Then there was Zelnorm (tegaserod), the partial 5-HT4 agonist from Basel, Switzerland-based Novartis AG. Approved in 2002 for IBS in women, Zelnorm was pulled from shelves in 2002 after cardiovascular risks came to light. The drug never returned to market.
Enter Xifaxan. "Doctors are pretty excited about it, in terms of having a different class of drug for IBS," and the well-characterized compound has proven safe - a big deal in any non-life-threatening disorder, Holder said, adding that patient compliance should be no problem, since Xifaxan brings no onerous side effects.
But Salix's unpartnered candidate faces would-be challengers moving through other pipelines. Its pricing, too, could limit use to the most severe IBS cases. Xifaxan's cost is about $11 per day when prescribed for traveler's diarrhea. Lotronex goes for $23.50 per day. "We don't think a drug that's going to be marketed at even half of [Lotronex's price] is going to do very well," Holder said.
Coming down the pike are IBS therapies from such firms as Tioga Pharmaceuticals Inc., of San Diego, spun out from Darmstadt, Germany-based Merck KgaA five years ago. Tioga has the kappa opioid receptor agonist asimadoline, which performed well in a Phase IIb trial.
Lexicon Pharmaceuticals Inc., of The Woodlands, Texas, has LX1031 gearing up for a Phase IIb study. In Phase IIa trials, the tryptophan hydroxylase inhibitor reduced pain in IBS over a four-week treatment period.
Asimadoline and LX1031 could be formidable rivals for Xifaxan, Holder said. Like Lotronex and Zelnorm, LX1031 takes aim at serotonin, but upstream from the receptors, which may mean fewer cardiovascular problems.
Of the three candidates, "LX1031 has the most promise, but you have to keep in mind [Lexicon] doesn't have late-stage clinical trial data," Holder said.
Salix company officials could not be reached, but JMP Securities analyst Charles Duncan was more sanguine than Holder about Xifaxan's chances in IBS. He predicted that if Salix, with or without a partner, could penetrate the primary-care physician offices - where half the IBS prescriptions are written - then Xifaxan could capture 20 percent of the market in patients with disease where constipation or diarrhea predominate.
A direct-to-consumer advertising campaign could broaden the potential, Duncan wrote in a research report. He pointed out that doomed Zelnorm's DTC push managed to boost doctor visits for IBS by 1 million after only three months, and the effort added about 400,000 diagnoses.
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