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

FDA review of NDAs for cancer and antiviral drugs "generally" take "less than a year" given the increases in the reviewing staff of the divisions that handle those drugs, FDA Office of Drug Evaluation I Director Robert Temple, MD, reported at the Drug Information Association's annual meeting in San Francisco on June 4. Last autumn, FDA Center for Drug Evaluation and Research Deputy Director Gerald Meyer highlighted the Oncology and Antiviral divisions as "clean desk" areas where NDAs can be reviewed upon submission to the agency ("The Pink Sheet" Nov. 13, 1989, p. 10). The staff increases in those divisions, Temple pointed out at the DIA meeting, permit FDA "to give the kind of early advice on the data needed and protocol design that can minimize development time." The theme of Temple's speech was "the tension between two goods" -- the early availability of drugs to treat serious illnesses when there is no other adequate therapy versus "the orderly scientific data-driven process of developing and evaluating new medicines." Temple described four ways in which effective and safe early access to promising agents can be accomplished. The first way is to "eliminate all needless administrative delays," Temple said. He pointed out that FDA has achieved this for AIDS and cancer drugs by speeding NDA review through the addition of more staff. Another way to accelerate reviews, Temple noted, is to "plan development better so that earlier approval can occur." When FDA does provide access to new drugs prior to approval, Temple suggested that persons responsible for the program should "remember that this use is investigational and make this clear to patients and the public, [and] also seek whenever possible to learn from the experience." Access to experimental drugs also could be widened through use of large, simple trials, Temple suggested. "There's growing interest in expanding access through use of low-tech or large, simple...trials." He explained that "these are studies that are well-designed, to try to minimize the data collected, and limit observations to those that are essential and not too exotic." The large studies "could explore different doses of a drug, or compare two treatments, or compare combination therapy with the component therapies." The concept of the large, simple trials received wide play in the lay-media following Temple's mention of the concept at the March 12-13 meeting of the Institute of Medicine's "Roundtable for the Development of Drugs and Vaccines Against AIDS." The large-trial approach, Temple said, "is well-established for [achieving] relatively short-term mortality endpoint[s] in cardiovascular trials, [and it] needs to be tested in other areas." He suggested that such an approach offers "very great" promise since the large number of patients that can be accrued "allows access and allows assessment of modest, but possibly important, differences between treatments as well as assessment of relatively rare adverse events." Temple pointed out that the "rapid rate of enrollment that can be achieved can give answers very quickly and the controlled nature of the study reminds all participants that they're still dealing with experimental treatments." During a session on the status of FDA's interim rule for "Procedures for Drugs Intended to Treat Life-Threatening and Severely Debilitating Illnesses," Temple asked Deborah Katz, RN, section chief, Regulatory Compliance, Division of AIDS, National Institute of Allergy and Infectious Diseases, to comment on the possibility of carrying out Treatment IND protocols "in a comparative way...using low-tech techniques to keep the questions simple, the forms short, and to compare things like two doses." Katz replied: "I think this is certainly something to be looked at; the concept of low-tech trials is not new." She added that when you "look at Bristol-Myers' expanded access program for ddI and you realize there are 10,000 patients on that, and then you think...if we had only randomized them to two doses, we might have all our information." Katz cautioned, however, that "I really believe the fundamental goal of a Treatment IND is to provide access and I think that when we start complicating access with [a] study, we might go back full circle and forget what the major goal is." Regarding FDA's use of the interim "expedited drug" rule, Temple noted that there have been a total of 144 drugs indentified as candidates for expedited development and review under the regulation. The FDAer compiled figures from FDA's latest quarterly report (March 31) on the drugs that are eligible for expedited treatment. The Anti-Viral Drug Division has 73 expedited review candidates, the Oncology & Pulmonary Drug Division has approximately 49, the Neuropharmacological Drug Division has six, the Gastrointestinal & Coagulation Drug Division has eight, the Metabolism & Endocrine Drug Division has four, the Anti-Infective Drug Division has two, and the Pilot Drug Evaluation Staff has two candidates. Temple added: "You'll also note that [the] Cardio-Renal [Division] just doesn't have drugs studied for mortality effects early on." * In a separate June 4 session on marketing exclusivity, FDA Associate Chief Counsel for Drugs Ann Witt indicated that FDA may require the inclusion of safety studies in full NDAs that are filed by generic firms to break an innovator product's exclusivity. At present, FDA allows companies to submit a safety analysis of adverse reactions with the innovator product in lieu of safety studies. Under Waxman/Hatch, a company can circumvent three-year and five-year marketing exclusivity awards to innovator products by conducting clinical trials and submitting a full NDA. FDA generally requires that firms repeat the innovator's studies, Witt said, with the exception of "some safety studies [that] might not have to be repeated" if a company submitted "appropriate analysis of adverse drug reactions" on the innovator drug. "On that question, I think we'll have to defer to the scientists in the agency, but it's possible we'll reconsider that." Witt told the DIA group that FDA has received a number of comments in response to the proposed rule to implement Title I of the Waxman/Hatch Act. Witt noted that companies have difficulty with FDA's interpretation of "what you have to do to be considered to have sponsored a study" to meet the criteria for receiving three-year exclusivity. "In our rule, you have to have been involved in the study before it was completed in some manner." Under FDA's current policy, Witt noted, "if you buy the rights to a drug together with the rights to a study, you will be considered to have sponsored that study." However, Witt added, "if you just buy the study, you won't be considered to have sponsored it." She explained that "buying the rights to a drug doesn't make you the sponsor anymore than buying the study. So on one level, I think we've already crossed the line away from the plain language of the word 'sponsor' and moved into something that seems a little bit fairer to use." And, Witt continued, "I think it's possible we'll reconsider whether we want to move even farther and permit other kinds of relationships between the person who conducted or sponsored the study and the person who ends up using it, to be considered sponsorship."

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