By: Jeet Guram, M.D., Senior Advisor to the Commissioner, R. Angelo de Claro, M.D., Associate Director for Global Clinical Sciences (Acting) in the Oncology Center of Excellence (OCE) and Director of the Division of Hematologic Malignancies 1 in the Office of Oncologic Diseases (OOD), Center for Drug Evaluation and Research (CDER), and Richard Pazdur, M.D., Director, OCE and Director (Acting) OOD, CDER
The U.S. Food and Drug Administration Oncology Center of Excellence (OCE), established in January 2017, has launched multiple initiatives consistent with its mission of achieving patient-centered regulatory decision-making through innovation and collaboration. One of these initiatives is Project Orbis, which began in May 2019, to facilitate faster patient access to innovative cancer therapies across multiple countries.
Project Orbis evolved from monthly teleconferences that FDA oncology held with international regulators over the past 15 years. From those interactions, it became clear that the United States often received new oncology product applications first ‒ sometimes months or even years before other countries did. Because pivotal clinical trials in oncology are often conducted internationally, a greater uniformity of new global standards of treatment could lead to the optimal design of these important trials.
To help facilitate oncology product submissions in other countries, without slowing down actions in the U.S., the OCE established the Project Orbis partnership. Pharmaceutical companies were asked to submit applications for clinically significant oncologic products to participating countries at the same time for concurrent review by their regulatory authorities. Six regulatory authorities have since agreed to participate in Project Orbis: Australia’s Therapeutic Goods Administration (TGA), Canada’s Health Canada (HC), Singapore’s Health Sciences Authority (HSA), Switzerland’s Swissmedic (SMC), Brazil’s Agencia Nacional de Vigilancia Sanitaria (ANVISA), and United Kingdom’s Medicines & Healthcare Products Regulatory Agency (MHRA). Representatives from each of the regulatory health authorities meet quarterly to review the overall status of the program and discuss potential improvements to processes. Such regular communications on the criteria for approvals in different countries benefits oncology product development by helping to improve and standardize the design of clinical trials worldwide.
Project Orbis is intended for high-impact oncology products – those products that have the potential to benefit patients the most. A driving factor behind establishing Project Orbis was to bring highly effective therapies to patients with cancer earlier, especially in countries where there would otherwise have been delays with regulatory submissions. Companies with applications seeking to participate are generally expected to meet the criteria for FDA’s priority review, which include a medical product that is intended to treat a serious condition and that, if approved, would provide a significant improvement in safety or effectiveness.
While the OCE serves as the primary coordinator for Project Orbis application selection and review, and develops a core review document to facilitate discussions, each country remains fully independent in making its regulatory decision and adherence with internal timelines.
The first regulatory action under Project Orbis took place on September 17, 2019, when the FDA announced the conclusion of a review conducted simultaneously with Australia and Canada. The review was for lenvatinib (Lenvima) in combination with pembrolizumab (Keytruda) for the treatment of patients with advanced endometrial carcinoma meeting certain criteria and disease progression following prior systemic therapy who were not candidates for curative surgery or radiation. The three regulatory health authorities reviewed the application in collaboration, which allowed them to identify any regulatory divergence among the review teams. This resulted in simultaneous approval decisions in all three countries. While the product labeling differed in format for each country, only minor differences were noted across the labels.
The OCE recently published summary data for the first full year of Project Orbis. From June 2019 to June 2020, a total of 60 oncology marketing applications (for either new molecular entities or supplements adding new indications) were received through the project, resulting in 38 approvals. New molecular entities, also known as new active substances, comprised 28% of the marketing applications received. Major oncology disease categories were represented in the submissions, with the most common oncology indications in non-small cell lung cancer (10 application submissions), followed by chronic lymphocytic leukemia (10), acute myeloid leukemia (6), endometrial cancer (6), breast cancer (5), and hepatocellular cancer (5).
The FDA and the participating countries look forward to continued collaborations through Project Orbis and potentially expanding the project to include additional countries and more varied product applications, including those that may involve complex issues such as companion diagnostics. Project Orbis has demonstrated that global regulatory collaboration is attainable and can deliver faster access to new therapies for patients with cancer. These core principles could inform the development of therapies more broadly, especially in settings where global collaboration would be critically important to public health, such as the ongoing COVID-19 pandemic.