WASHINGTON _ Cancer drug manufacturers will have to submitclear evidence that their products result in tumor shrinkage or otherquantifiable clinical benefit in order to obtain product approval usingthe FDA's recently announced accelerated approval process forcancer drugs.

FDA officials made it clear at the April 19, 1996, meeting of theOncologic Drugs Advisory Committee (ODAC) that drugmanufacturers will have to submit proof using radiographs or similarevidence of solid tumor shrinkage or "meaningful remission inhematological malignancies," said Robert Justice, medical officer atthe FDA's Center for Drug Evaluation and Research.

The briefing by Justice and Robert Temple, director of the Office ofDrug Evaluation, was the first detailed explanation of the FDA's newpolicy announced at the White House last month to speed cancerdrugs to market and to expand access to investigational therapies.

The FDA will not accept surrogate markers to demonstrate clinicalbenefit, Justice said. "But that doesn't mean that we won't sometimein the future."

FDA officials are concerned that surrogate markers do not alwayscorrelate with clinical benefit and often give clinicians mixed signalsabout disease progression, Temple said. "Right now we want to usebona fide, unequivocal end points."

Failure to demonstrate tumor shrinkage could easily derail a producton accelerated approval. "Accelerated approval can be withdrawnmore easily than the normal new drug application approval process ifthe manufacturer fails to show clinical benefit," said Justice.

FDA administrative procedures provide for a hearing and discussionwith the pertinent advisory committee before accelerated approvalstatus can be withdrawn from a product, Justice said.

He stressed that the accelerated approval process for cancer drugsalso applied to supplemental applications submitted to support newindications for use.

Despite the White House announcement, much of the acceleratedapproval process has not changed. "The agency's final decision onaccelerated approval will be based on a risk/benefit assessment, thedegree of toxicity of the therapy, adequacy of the design of theclinical trials and that the Phase III trials show a clear benefit overexisting therapy," Justice said.

He said the FDA also is encouraging manufacturers to submitapplications for second indications. "We rarely have applications fora second indication," Temple said. "If the application is targeted atpatients with refractory disease, manufacturers will be eligible for theaccelerated approval process."

In the past, cancer drugs were reviewed by the agency to determine ifthey produced an effect on the patient's survival, quality of life andabatement of symptoms, as well as objective measures of diseaseregression. In addition, if a drug produced a partial response in thepatient, such as incomplete tumor shrinkage, these results werecorrelated with the other approval criteria. The revised approvalcriteria now will enable cancer drug manufacturers to gain marketingclearance under the accelerated approval process if they candemonstrate objective evidence of tumor shrinkage "allowingadditional evidence of increased survival and/or improved quality oflife associated with that therapy to be demonstrated later," accordingto the FDA.

FDA's new initiative also expands patient access to treatmentinvestigational new drug (IND) protocols and compassionate useprotocols which provide treatment to single patients. The expandedaccess program permits patients access to promising but not yetapproved cancer therapies that are in clinical trials. The FDA iscontacting manufacturers to submit expanded access protocols fortherapies that are already approved by overseas drug regulatoryagencies.

The agency is actively recruiting cancer survivors to serve on ODACand other FDA advisory committees that deal with cancer treatmentdrugs.

Finally, the FDA will reduce the number of IND applicationsrequired for additional studies of already approved therapies butapproval by the institutional review board and provision of informedconsent must be assured by the manufacturer, Temple said at theODAC meeting. n

-- Michele L. Robinson Special To BioWorld Today

(c) 1997 American Health Consultants. All rights reserved.