FDA’s Project Orbis: Trendsetter or One-off
September 26, 2019
David Shoemaker, PhD, SVP R&D, has over 25 years of experience in pharmaceutical product development. He has served as a Program Leader or Advisor for multi-disciplinary program teams and has been involved with ensuring products meet regulatory standards at all stages of the development process.
With the announcement of Project Orbis, FDA’s Oncology Center of Excellence (OCE) excited both patients and the pharmaceutical industry with the program’s future possibilities for collaborative regulatory authority interaction in accelerating product approvals worldwide. The intent of Project Orbis is to provide a structure for collaboration between international regulatory authorities on the evaluation and marketing approval of oncology drugs and this possibility was first manifest by the simultaneous approval by the US FDA, Health Canada (HC), and Australian Therapeutic Goods Administration (TGA) of a combination regimen of two oncology drugs, Lenvima (lenvatinib) and Keytruda (pembrolizumab), for the treatment of advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation.
The three regulatory authorities involved are to be congratulated for accomplishing this feat for a high profile program where patients are in dire need of the regimen. These two drugs were approved by the accelerated approval pathway in the US using the Real-Time Oncology Review pilot and its accompanying Assessment Aid program and provisional pathway in Australia. The approval was based on tumor response rate and durability of response. Patients were treated with 20 mg lenvatinib orally once daily in combination with 200 mg pembrolizumab intravenously every three weeks until treatment termination due to toxicity or disease progression.
So the question immediately comes to mind as to whether this is the tip of the iceberg for process improvement for future coordinated international regulatory marketing approvals or is this an isolated incident where all the stars were aligned. Inasmuch as these products were already approved on their own merits for treatment of several different types of cancer including differentiated thyroid, liver, and renal in combination with everolimus in the case of lenvatinib and melanoma, metastatic non-small cell lung, head and neck squamous cell, classical Hodgkin Lymphoma, urothelial, microsatellite instability-high, gastric, small cell lung, primary mediastinal large B-cell lymphoma, esophageal, cervical, hepatocellular, merkel cell, and renal in the case of pembrolizumab, this is a case where regulatory authorities have a great deal of familiarity with these compounds and coordinated expedited approval between international regulators should be expected.
Of course the question of how much interaction these different regulatory authorities have with one another is critical to determining how likely these coordinated approvals will be regardless of their familiarity with the compound. This collaboration between the US, Canadian, and Australian regulatory authorities was no doubt facilitated by the monthly Oncology International Cluster Calls held between the FDA, European Medicines Agency, HC, Japan’s Pharmaceuticals and Medical Device Agency, Swissmedic, and the TGA. It seems that while this is a wonderful milestone of having a life-saving regimen approved simultaneously by three international regulatory bodies, the likelihood is it will be a long time before this coordination is repeated for any initial marketing applications in a therapeutic indication other than oncology. Nonetheless, the OCE is once again paving the way for innovation at the FDA.