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

CENTOCOR MUST PERFORM SECOND TRIAL OF CENTOXIN before FDA will resume its review of the company's product license application for the monoclonal antibody product for septic shock. In an unusual public comment on the status of Centoxin, FDA said April 17 that it has "requested that Centocor submit data from an additional well-controlled trial before further consideration of the PLA for HA-1A for the treatment of gram negative sepsis." The FDA announcement follows on the heels of an April 15 company release revealing that FDA had deemed currently available data for Centoxin as "insufficient evidence of efficacy for approval at this time." FDA's Vaccines and Related Biological Products Advisory Committee had found the product safe and effective at a meeting last September ("The Pink Sheet" Sept. 9, 1991, p. 14). Centocor explained that FDA expressed concern that an analysis of "some interim efficacy data," which took place "before a revised analytical plan was finalized," may have influenced the results of the company's only large scale trial of HA-1A. Centocor submitted data on 616 patients for review by the advisory committee. "Centocor's claim of efficacy was based on an analysis of a subset of 200 study patients with sepsis ultimately found to have gram-negative bacterial infections in the bloodstream." The study endpoint in the original protocol was 14 days. "There was no statistically significant difference in survival between treated and placebo groups 14 days after treatment," according to the FDA statement. Prior to completion of the study, Centocor submitted a revised analytical plan adding a new primary endpoint, FDA said: survival over 28 days. During that period, 45 of 95 placebo-treated patients died, compared with 32 of 105 HA-1A treated patients, a difference of "marginal statistical significance" according to FDA but great enough to garner the committee's guarded recommendation. At the time of the advisory committee meeting, the agency was not aware of the interim analysis. "Subsequent to this meeting, FDA learned that certain Centocor staff were aware of the results of some interim analyses prior to the final submission to the agency of the revised analytical plan," FDA said. "Because of the potential for introduction of bias, results of analyses based upon this plan cannot be accepted." Centocor emphasized that company "personnel continue to work with the agency's staff to identify the most effective manner in which to develop" the required additional data." The company says it remains "hopeful that approval can be achieved later this year." Since receiving the committee's favorable recommendation, Centocor has been gearing up for approval of the product: the company expanded its U.S. Centoxin sales force by forty sales reps during the week of Dec. 30-Jan. 3, increasing the total to 200 ("The Pink Sheet" Jan. 13, T&G-5).

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