Pink Sheet is part of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC’s registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 8860726.

This copy is for your personal, non-commercial use. For high-quality copies or electronic reprints for distribution to colleagues or customers, please call +44 (0) 20 3377 3183

Printed By



Executive Summary

CHOLYBAR's TRIGLYCERIDE DIFFERENCE v. QUESTRAN in Warner-Lambert's bioequivalence study resulted from a dosing bias in one center, W-L maintained in a March 7 letter to FDA. Warner-Lambert submitted the letter in response to Bristol-Myer's Dec. 9 citizen's petition requesting that FDA withdraw approval of the Cholybar ANDA pending further studies by the company. The Bristol-Myers petition alleged that the bioequivalence of the two products has not been established, since Warner-Lambert's studies show higher increases in triglycerides and very low density lipoproteins with Cholybar ("The Pink Sheet" Jan. 2, T&G-9). The Warner-Lambert trial was a four-week randomized crossover study comparing its Cholybar to B-M's Questran. Six centers completed the study. However, Warner-Lambert said that patients in one center were not given the required doses of Questran, receiving less cholestyramine than the Cholybar group. While the medical reviewer in FDA's metabolism division excluded this center in her analysis of the data, the reviewer from the bioequivalence division included the center, thereby skewing his data, Warner-Lambert maintained. The analysis by the bioequivalence division reviewer determined that "on a six-center, four week basis, the difference in triglyceride elevation was significantly different" with an adjusted mean percentage change of 40.5% for Cholybar and 18.2% for Questran, the firm noted. However, Warner-Lambert maintained that this result is "inconsequential," because the reviewer "did not take into account the statistically significant center interaction [and] it is generally recognized that there is a dose related and temporally variable increase in triglycerides with cholestyramine resin use." Warner-Lambert pointed out that the five-center analysis shows "there was no statistically significant difference in elevation of triglycerides." The letter asserts that "additional statistical analyses of triglycerides confirms that there is no difference between the two products" in that "median values for triglyceride elevations were virtually identical (Cholybar 21.5 mg/dl and Questran 21.6 mg/dl)." In response to Bristol-Myers' argument that Cholybar may be unsafe because of the higher rate of gastrointestinal adverse effects among the patients taking Cholybar, Warner-Lambert submitted an analysis of adverse events for all 98 patients exposed to cholestyramine to FDA. "The differences in adverse events during crossover and in dropouts do not mean, as Bristol contends, that patients are at a higher risk of 'severe gastrointestinal complications' with Cholybar," the company stated. Warner-Lambert attributed the differences to several possible biases: "more patients were exposed to Cholybar during crossover; Cholybar users who dropped out during initial treatment would likely have had a similar reaction to Questran had they been crossed over; and 60.2% of the patient population were prior powdered resin users . . . these patients were more likely to be intolerant of a new dosage form."

You may also be interested in...

Part D Discount Liability Coming Into Focus: CMS Releases Drug Cost Data

Newly released Medicare Part D data sheds light on the sales hit that branded pharmaceutical manufacturers will face when the coverage gap discount program gets under way in 2011

FDA Skin Infections Guidance Spurs Debate On Endpoint Relevance

FDA appears headed for a showdown with clinicians and the pharmaceutical industry over the proposed new clinical trial endpoints for acute bacterial skin and skin structure infections, the guidance's approach for justifying a non-inferiority margin and proposed changes in the types of patients that should be enrolled in trials

Shire Hopes To Sow Future Deals With $50M Venture Fund

Specialty drug maker Shire has quietly begun scouting deals with a brand-new $50 million venture fund, the latest of several in-house investment arms to launch with their parent company's pipelines, not profits, as the measure of their worth




Ask The Analyst

Ask the Analyst is free for subscribers.  Submit your question and one of our analysts will be in touch.

Your question has been successfully sent to the email address below and we will get back as soon as possible. my@email.address.

All fields are required.

Please make sure all fields are completed.

Please make sure you have filled out all fields

Please make sure you have filled out all fields

Please enter a valid e-mail address

Please enter a valid Phone Number

Ask your question to our analysts