FDA's process for facilitating expanded access requests is a prime focus of reformers. The agency permits clinical trial sponsors
to amend an investigational new drug application (IND) to grant patients access to experimental drugs for treatment purposes.
Patients can't apply for such access; the request has to come from the sponsor, physician investigator, or a qualified treating
physician, either for a single patient or a small group (up to 100 patients). The expanded access IND requires evidence that
the individual(s) have serious or life-threatening conditions, do not qualify to participate in a clinical trial, have no
other treatment options available, and that potential benefits are likely to outweigh possible risks.
Details on the process are provided on FDA's website and in a May 2013 Q&A guidance on expanded access to investigational
drugs for treatment use. Jim Robinson, president of Astellas US, would like to see additional guidance on criteria for vetting
requests for compassionate use, noting that demands for early access will only increase with some 3,000 drugs in development
for cancer and other serious conditions.
FDA's Office of Health and Constituent Affairs, which provides information to health professionals and patients on expanded
access policies and procedures, reports that the agency receives about 1,000 expanded access INDs and access protocols each
year and approves virtually all of them. The vetting process includes review by an institutional review board (IRB) to ensure
adequate informed consent, and by the relevant new drug review division.
FDA officials sometimes convey patient requests to pharmaceutical companies and offer assistance to willing firms and physicians
in filing necessary information and navigating the application process, explains Patient Liaison Program director Richard
Klein. Because the purpose of these programs is treatment, and not research, sponsors don't have to submit efficacy data from
an expanded access study, but must report serious adverse events.
While FDA permits sponsors to charge patients for the cost of drugs provided under compassionate use, this provision is seldom
used. Companies usually prefer to keep confidential information on production processes and costs, and limited supply is a
larger concern than gaining revenue.
FDA's desire for flexibility can be seen in its handling of the Chimerix case. Amidst the public demand for access to brincidofovir
for Josh Hardy, FDA worked with Chimerix to approve a 20-patient open-label clinical trial for treatment of adenovirus infection
in immunocompromised pediatric patients. The company thus avoided a massive open-access program, and gained a strategy that
it hopes will lead to a Phase III trial for this indication. Meanwhile, Chimerix is continuing its main development program
(under new company leadership), which seeks accelerated approval of the drug for prevention of the more common cytomegalovirus
(CMV) infection in adult bone marrow transplant patients. Chimerix launched its Phase III SUPPRESS trial last year at 40 transplant
centers, with an eye to enrolling 450 patients, 150 receiving placebo; initial results are expected by mid-2015.
Although FDA and the sponsor addressed this compassionate use case successfully, there's continued pressure for new approaches.
A bill before Congress would permit the manufacture, importation, and distribution of unapproved investigational products
to terminally ill patients. State legislatures are considering "right to try" bills, as seen in an Arizona measure that permits
physicians to prescribe investigational drugs for certain terminally ill patients. Such proposals raise constitutional questions
about the right of states to challenge federal drug approval policies, an issue central to past lawsuits challenging FDA interference
in patient treatment.
Faster approval of important new medicines could address some early-access concerns, a goal for regulators and sponsors alike.
FDA held a public hearing in February 2013 on strategies for improving the accelerated approval process and whether FDA needs
additional tools and authority to move promising therapies through the regulatory process—issues that will be explored further.
Jill Wechsler is Pharm Exec's Washington correspondent. She can be reached at email@example.com