Project Orbis Enables First International Approval in U.S., Canada, Australia

As part of the new Project Orbis, the national health regulators of the United States, Canada, and Australia together announced they were jointly approving a combination immunotherapy for a particular form of endometrial cancer on Tuesday.

The program is envisioned as a way for governments to collaboratively decide upon supplemental oncology approvals for previously approved therapies. But Project Orbis could also eventually speed up new drug applications and original biologics license applications, officials said.

“As Project Orbis expands, we look forward to welcoming additional international partners to collaborate with us in this important initiative as we work to help further serve the global patient community,” said acting FDA commissioner Ned Sharpless, M.D., in a statement on Tuesday.

Experts told Cancer Network™ that the concept is a viable way to increase access to new treatments – but not necessarily get the cost covered in some places.

The first Orbis approval was made jointly by the FDA and its counterparts – the Australian Therapeutic Goods Administration (TGA) and Health Canada.

The accelerated approval was for lenvatinib (Lenvima) in combination with pembrolizumab (Keytruda), for the treatment of patients with advanced endometrial carcinoma whose tumors are not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). The patients’ disease also must meet specific criteria: it must have progressed following prior systemic therapy, and curative surgery or radiation are not options.

Both drugs were independently approved for different indications by the FDA, with Keytruda approved for advanced melanoma in 2014 and Lenvima the following year for a specific kind of thyroid cancer. Both have since been approved for additional tumor indications.   

The combination of the two for endometrial cancer – in the inner lining of the uterus – was granted several special considerations for approval. Accelerated approval, priority review, and breakthrough therapy designation were all granted as the FDA conducted its review under the Oncology Center of Excellence’s Real-Time Oncology Review (RTOR) pilot program.

“RTOR, and its accompanying assessment aid, facilitated discussions among the regulatory agencies, expediting the approval in three countries,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence, as part of the agency’s statement on Tuesday. “These applications were approved three months prior to the FDA goal date.”

The international collaboration efforts have been in process for 15 years already.

The FDA’s Office of Hematology and Oncology Products started holding regular teleconferences with counterparts across the world in 2004; currently the Americans have a monthly teleconference with their counterparts in Australia, Canada, the European Medicines Agency, the Japanese Pharmaceuticals and Medical Devices Agency, and Swissmedic in Switzerland. The FDA also has a quarterly meeting with the Chinese National Medical Products Administration to discuss regulatory issues, officials said.

A bioethicist said the approval process represented in Tuesday’s announcement is actually a “great idea” for medicine in general – and patients in particular. Arthur Caplan, Ph.D. the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics in the Department of Population Health at NYU Langone Health, told Cancer Network™ that it makes sense for these drugs to be fast-tracked.

“I think this is a great idea,” said Caplan. “The countries they’re collaborating with have very high standards for trials, evidence, and approvals. There’s obviously some differences in terms of pace.”

One interesting factor not mentioned in the announcement, however, is the question of payment. Some of the countries, like single-payer-system Canada, may hold off covering certain early-access treatments until efficacy is further proven, and a further track record is more established, Caplan explained.

“It’s not like here, where you have 10 different payers you have to fight with to get something paid for once it’s approved,” Caplan said. “There it’s a national health system, and they often are tougher on what evidence it’s going to take to get them to cover a drug. That isn’t the evidence it takes to get it approved.”