WASHINGTON -- Gene therapy companies won a small victoryin the battle against bureaucracy when the Recombinant DNAAdvisory Committee (RAC) of the National Institutes of Health(NIH) agreed last week on guidelines for certain clinical trialprotocols to receive accelerated review.
The accelerated-approval track would exempt some genetherapy trials from full review by RAC if the protocolapplication is judged by the committee's chairman to fall intoone of seven categories (see box on page 6). The sevencategories were designated as "minor actions."
Since RAC meets only three to four times per year, companieshave warned that the lengthy process of full review for everyprotocol wastes precious time. The only differences betweensome new protocols and protocols previously approved by RACare the addition of a new principal investigator or study site.Under the new rules, such protocols would be eligible foraccelerated review.
"RAC should be focusing on cutting-edge issues, not reviewingthe 10th cystic fibrosis protocol," said Alan Goldhammer,director of technical affairs at the Biotechnology IndustryOrganization (BIO) in Washington, D.C. While Goldhammer saidhe welcomed the new guidelines, it's clear they may not be asinclusive as some in the industry had hoped.
For example, Goldhammer wrote a letter to RAC last Nov. 3suggesting that when a RAC-approved gene therapy agentadvances from a Phase I to a Phase II or III trial, it should beeligible for accelerated review. According to RAC memberStephen Straus, chief of the Laboratory of Clinical Investigationat the National Institute of Allergy and Infectious Diseases(NIAID), such a change is still beyond RAC's "comfort level."
To date, only Phase I protocols have come before RAC becausethe field is still so new. Straus said it's possible that once thecommittee has sufficient experience approving the transitionfrom Phase I trials to Phase II and beyond, it may broaden theguidelines for accelerated review even further.
Straus said RAC's primary role is to serve as the guardian ofsafety in new gene therapy agents, not the arbiter or guarantorof efficacy. Although RAC only has formal jurisdiction overgene therapy trials that are funded by the NIH, it has becomeindustry practice to submit any new gene therapy trial to thecommittee. RAC represents the only public forum for airing thescientific and social issues involved in gene therapy, and drugcompanies want RAC's blessing.
However, final authority for safety and efficacy in allexperimental drug trials resides with the FDA. All gene therapyprotocols approved by RAC also must be approved by the FDAthrough the traditional investigational new drug (IND)application process before patient enrollment can begin. Andwhile companies have complained about RAC, some say theFDA has been the real bottleneck for gene therapy.
"RAC is not the rate-limiting step," said RAC member RobertsonParkman, head of research immunology at Children's Hospitalof Los Angeles. "In the last three years, waiting for RACapproval has never once held up the clinical implementation ofa protocol."
Parkman said that the lag between RAC approval and FDAapproval is growing, not shrinking. Acknowledging thatcompanies have been pushing for accelerated review, he said,"It's not going to make the difference they think it's going tomake because they'll still have to deal with the FDA."
Parkman told BioWorld that only two or three protocols overthe past three years would have qualified for acceleratedreview even if the new rules had been in place all along. Hesaid the guidelines were designed primarily as a triagemechanism for RAC as it faces increasing numbers of protocolsin the future.
Parkman conceded that RAC may have to meet more often,noting that the committee's equivalent in England meets sixtimes a year although it has fewer protocols to review.
BIO's Goldhammer agreed that a potential problem is looming."There's a real potential that if this technology explodes, aseveryone thinks it will, RAC will be overwhelmed," he said."What will happen when all of the current products go intoPhase II trials and even more new products attempt to enterPhase I trials? The transition from Phase I to II to III may befaster at the FDA. Our question is, is RAC really equipped tohandle that?"
-- Lisa Piercey Washington Editor
(c) 1997 American Health Consultants. All rights reserved.