Glaxo Wellcome Tritec for H. pylori approved Aug. 8.

GLAXO WELLCOME TRITEC ERA BEGINS: AGENT WILL BE AVAILABLE IN SEPTEMBER following Aug. 8 FDA approval of ranitidine bismuth citrate for use in combination with Abbott's Biaxin (clarithromycin) to treat active duodenal ulcers associated with Helicobacter pylori. Biaxin and Astra Merck's Prilosec (omeprazole) were approved as a combination April 18 and April 15, respectively ("The Pink Sheet" April 22, p. 17).

The approval of Tritec will complete the transition away from Zantac (ranitidine) as Glaxo Wellcome's primary promotional focus.

Tritec will be marketed by the same sales force that markets prescription Zantac; the force has about 500 reps ("The Pink Sheet" Aug. 5, p. 11). The company has been priming the market with "coming soon" ads for Tritec.

Glaxo does not have immediate plans for direct-to-consumer advertising, although it eventually will introduce patient educational materials. Glaxo could work with a lay or professional organization in that endeavor, the company indicated.

Tritec will have a four-week dosing regimen: patients should take a 400 mg tablet b.i.d.; Biaxin 500 mg t.i.d. should be added for the first two weeks. Tritec is manufactured in the U.K. with secondary manufacturing in Zebulon, N.C.

By adding bismuth citrate to ranitidine to formulate Tritec, Glaxo retains exclusivity for a prescription ulcer therapy after July 1997, when generic ranitidine could enter the U.S. market. A July 1 federal court ruling in favor of Novopharm would allow the generic company to market Form 1 ranitidine; Glaxo markets Form 2, which is patent-protected through 2002. Glaxo is appealing the decision ("The Pink Sheet" July 15, p. 3). Ranitidine bismuth citrate weakens the H. pylori bacteria in addition to suppressing acid, Glaxo said.

Glaxo had maintained that Tritec has antimicrobial properties. At Tritec's December 1995 advisory committee review, Glaxo said RBC had synergistic activity against resistant strains of H. pylori and that therapy could diminish acquisition of clinical resistance. However, the company lacked microbiological susceptibility data ("The Pink Sheet" Dec. 18, 1995, p. 3).

A Phase IV study will assess Glaxo's assertions. According to FDA's approval letter, the company will conduct a clinical trial in "patients with active duodenal ulcers and/or ulcer diathesis" and H. pylori. The study will include a minimum of two arms: Tritec 400 mg b.i.d. plus Biaxin 500 mg t.i.d. and Zantac 150 mg b.i.d. plus Biaxin 500 mg t.i.d.

"The study should assess the microbiological success among patients with pre-study clarithromycin-resistant strains and the potential significance of emerging clarithromycin resistance during treatment," the letter states. Compliance data will be collected to study "the relationship between compliance and emerging clarithromycin resistance."

Glaxo faces the challenge of promoting Tritec not only against Biaxin/Prilosec, which has a head start in market penetration, but against ranitidine itself. The role of H. pylori has been well-publicized, and ranitidine has been studied in a variety of regimens for its eradication.

A National Institutes of Health consensus panel concluded that triple therapy with metronidazole, amoxicillin and an H2 antagonist was one of three regimens effective against H. pylori. The generic availability of the antibiotics, and the pending generics of ranitidine, could make such a combination more desirable from a cost-containment standpoint than Tritec/Biaxin, both of which are under patent. The FDA advisory committee recommended against a Tritec/amoxicillin regimen.