Applied Clinical Trials
The agency's Oncology Center of Excellence continues to build on successes in bringing innovative cancer drugs to patients through accelerated development and speedy approval of breakthrough treatments.
FDA’s Oncology Center of Excellence (OCE) continues to build on its successes in bringing innovative cancer therapies to patients through accelerated development and speedy approval of breakthrough treatments. Under the leadership of director Richard Pazdur, and benefitting from strong support from patient advocates and
Congressional policymakers, OCE is expanding pilot projects and international collaborations to further support access to new medicines. At the same time, FDA officials are working to ensure postapproval assessment of the safety and efficacy of new products that come to market based on limited clinical trials with few patients.
OCE marked its third anniversary in February with a public workshop to review ongoing projects and future plans, many of them described in OCE’s annual report for 2019.1 FDA approved 11 new molecular entities (NMEs) for oncology last year plus multiple supplemental indications, biosimilars, and medical devices. The agency’s Real-Time Oncology Review (RTOR) initiative aims to accelerate these activities further by enabling sponsors to grant FDA staffers access to certain clinical data prior to submission of an official application, as a way to address questions and issues in advance.
As patient advocates continue to press for expanded access to investigational drugs, a tricky issue raised at the Feb. 5 workshop is whether such early access should apply to unapproved indications of an approved cancer therapy. Pazdur noted that FDA policies do not rule out such agreements and that the agency is willing to process a request from a physician, although sponsors are less likely to support such actions.
OCE also aims to better assess safety reports from clinical trials through more effective tracking and review of safety information. To this end, FDA’s Project Protect encourages the submission of investigational new drug (IND) safety reports in a standard electronic format established by the International Council on Harmonization (ICH).
The development of pediatric cancer therapies is another high-profile goal. FDA issued draft guidance in December outlining the conduct of pediatric studies for targeted oncology drugs, and Congressional leaders and patient advocates back further legislation to advance this area.
Additional FDA guidances related to oncology R&D address testing of in vitro diagnostics, using placebos and blinding in randomized controlled cancer trials, reproductive toxicity testing for oncology pharmaceuticals, patient eligibility in different cancer studies, and developing therapies for specific cancer indications.
OCE also is advancing joint international activities to facilitate access to cancer therapies around the world. FDA officials and regulators in Europe and other advanced countries have been discussing for the past decade ways to gain greater uniformity in global standards for cancer treatment and for conducting oncology clinical trials. One result is the current Project Orbis, which was launched officially in September 2019 with the announcement of a simultaneous review and approval of an oncology supplemental application by FDA, Health Canada, and the Australian Therapeutic Goods Administration.
Each authority approved its own label and utilized accelerated/conditional approval procedures, and more joint applications are on the agenda.
To facilitate FDA product approvals, OCE supports a collaborative process for working with medical reviewers and scientists in FDA product centers. This involves teaming up with offices for cellular and gene therapy and for vaccines in the Center for Biologics Evaluation and Research (CBER) and with relevant review groups for medical devices. The ongoing reorganization of the Office of New Drugs (OND) in the Center for Drug Evaluation and Research (CDER) will alter its oversight of the many applications for oncology drugs and biologics.
OND now has a new Office of Oncologic Disease (OOD), with three divisions of oncology for different cancer treatments, plus two divisions to review drugs for hematologic malignancies.
Such changes aim to create more therapeutically aligned and disease-focused divisions of manageable size able to handle the very full pipeline of new cancer therapies slated to seek FDA advice and market approval. CDER continues to update information on which the OND division will review which product applications, as the reorganization process continues.2
Under the OCE-CDER joint review system for all oncology products, sponsors submit applications to the appropriate product center, which decides whether expedited development and review is warranted. Those products that qualify will have a joint review by a Medical Oncology Review and Evaluation (MORE) team with specialists from OCE and other Centers. The aim is to provide a unified clinical review and promote agreement on standards for breakthrough therapies and fast-track designations.
This oncology team review approach fits with CDER’s new integrated review program, which brings together groups of reviewers with expertise in the various aspects of development of the specific product. The process aims to meet goals for 30-day IND reviews, as well as timeframes for market applications and supplements.
These organizational changes aim to facilitate the work of the more than 100 medical and hematologic oncologists at FDA in assessing advances in the scientific understanding of disease, particularly cancer. Such changes add to the agency’s confidence in justifying accelerated approval of treatments for rare and serious conditions based on identification of molecular drivers and evidence of dramatic response. In such cases, a small, single-arm clinical trial may suffice to support approval, along with timely confirmation of early results through robust clinical data to validate and confirm early benefits.
Jill Wechsler is the Washington Correspondent for Applied Clinical Trials