Expanded IND Access: FDA Seems Resolved, Leaving Many Questions For Firms
Executive Summary
FDA seems set on implementing its proposed rules on patient access to investigational drugs despite industry-wide concern
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FDA seems set on implementing its proposed rules on patient access to investigational drugs despite industry-wide concern. At an educational session held during the American Society of Clinical Oncology conference in Chicago, criteria for the agency's final regulations were presented alongside a laundry list of industry anxieties. Ann Farrell, deputy director of FDA's Division of Drug Oncology Products, said the final regulations include a list of criteria that would make a patient eligible for access to an investigational drug: The disease must be serious or life-threatening There must be an ongoing clinical investigation There must be no comparable or satisfactory alternative available to the patient The sponsor must intend to market the product The probable risk from the drug must not exceed the probable risk from the disease The potential benefit must justify the potential risk Farrell's comments indicate the proposed rule will be implemented largely unchanged. "When the final rule is published it will say that the potential benefit must justify the potential risk and that may depend on the stage of the drug development," she said. "The new regulations clarify that the access to investigational agents is through a licensed physician and not a major medical center," Farrell noted. FDA issued the proposed rule in December 2006 during an ultimately successful court battle with the Abigail Alliance, a group that had sued the agency to try to loosen its restrictions on access to experimental medicines (1 (Also see "FDA Expanded Access Proposals Too Narrow For Patient Advocates" - Pink Sheet, 18 Dec, 2006.), p. 12). The agency said it did not have an estimate for when it would be finalized, although HHS' semiannual regulatory agenda lists October as the projected completion date (2 'The Pink Sheet,' May 12, 2008, In Brief). The proposed reg failed to satisfy the Abigail Alliance, which eventually lost its challenge to the agency on appeal (3 , p. 23), but the rule also raised significant concerns for drug sponsors. There is "crashing uniform agreement that expanded access programs are not in the best interest of scientific drug development," AstraZeneca's Judith Ochs said at the ASCO panel. "I don't think anyone would disagree with that basic premise." Included in the 119 comments FDA received about expanded access regulations, pharmaceutical and biotechnology industries said the rules would impede the development of drugs and incentives for patients to enroll in key clinical trials, as well as create more administrative and economic burden. Expanded Access Spells Challenges For Industry FDA hopes the new regulations will help with the continuing problems of equal access, public awareness and issues surrounding charging that are unclear (see chart: " 4 FDA Strikes Its Balance "). It also expects the regulations to decrease the administrative burden by streamlining submission requirements and procedures. But for pharmaceutical companies, the new regulations only mean the challenge of limiting access to investigational drugs continues (see chart: " 5 What Rx Firms Ask Themselves About Expanded Access "). For starters, different countries have different trial requirements, meaning pharmaceutical companies must adhere to different policies in each region of the world. In Italy, for example, a drug must have Phase II safety and efficacy data, and in France, the sponsor must guarantee the program will last only one year. Expanded access comes with a price tag. The strain on company resources is estimated to be anywhere from $1 million to hundreds of millions of dollars, said Ochs, pointing out that the financial commitment is typically for an "unknown period of time." An enormous disincentive for drug companies to allow expanded access programs is the unknown safety risks it presents to patients. Indeed, the failure rate of Phase I oncology trials in phenomenal. Ezekiel Emanual, chair of the Department of Bioethics at the National Institutes of Health's Clinical Center, presented failure rate statistics that showed for every 100 drugs that enter oncology Phase I trials, only 58 go on to Phase II, and only five or so go on to approval. Therefore, he explained, if patients were allowed access to any investigational drug they wanted, they would be exposed to 11 ineffective drugs for every one effective drug. "If you go through all the effort to do all the pre-clinical development and all the testing we do, it would be foolish to go ahead and run a trial that is not scientifically valid and which won't get you approval," said Ochs. Furthermore, in expanded access programs, some of the patients are "imminently terminal," said Ochs, which can increase the risk of getting what she calls a "false-positive" safety risk. "It could conceivably delay or even derail your whole program if investigators feel that there is a problem here." FDA has emphasized that it would not "penalize" sponsors for problems seen with products under expanded access programs (6 'The Pink Sheet,' March 17, 2008, In Brief). Early access to investigational drugs also may result in a large number of safety letters, said Ochs, which in turn means IRB notification for those sites that are participating in the program. The letters not only involve an additional amount of administrative work, but can make a safe drug perceived to be otherwise. "You're looking at a process which is very high-risk in terms of getting to the endpoint and the two obstacles that get in your way are efficacy and safety," she said. Ochs pointed out that while companies feel a little bit safer when exploring drugs not first in class, they all strive to develop first-in-class agents, and the unknown clinical experience with those only adds to the safety concerns. Finally, if an investigational drug patients are using is approved, the sponsor must be prepared with a program to help patients obtain the drug commercially. "You can't simply take a drug away from a patient who is benefiting from that drug," said Ochs. As firms consider the moral, regulatory and public relations aspects of these issues, the Abigail Alliance continues to press for broader access to drugs through legislation. The Access, Compassion, Care, and Ethics for Seriously Ill Patients Act, sponsored by Sen. Sam Brownback, R-Kan., and Rep. Diane Watson, D-Calif., was reintroduced this month (7 'The Pink Sheet,' June 2, 2008, In Brief). - Lauren Smith ([email protected]) |