Skip to content

Pink Sheet – Does Imlygic Make The Case For FDA Oncology Center Of Excellence?

Pink Sheet – Does Imlygic Make The Case For FDA Oncology Center Of Excellence?

Executive Summary

Products like Amgen’s viral therapy for melanoma could benefit under proposals to replace FDA’s modality-based organization with disease-specific centers. FDA’s biologics center proved itself capable of reviewing the oncologic, but the drugs center already had extensive recent experience with the fast-changing melanoma market.

The FDA review of Amgen Inc.’s Imlygic could provide support for advocates of disease-specific reorganization of some of the agency’s review functions.

Cancer vaccines like Imlygic remained at the Center for Biologics Evaluation and Research when FDA moved regulation of therapeutic biologics to the Center for Drug Evaluation and Research in 2004. And while scientific advances have made oncology by far the busiest segment of CDER’s drug review activity, much less experience has accrued on the CBER side.

 Imlygic is only the second cancer treatment approved by CBER’s Office of Cellular, Tissue and Gene Therapies. The first came six years ago, when Dendreon Corp.’s pioneering autologous immunotherapy (and notable commercial disappointment) Provenge received approval in prostate cancer.

The idea of organizing FDA reviews by disease instead of by modality (drug, biologic or device) has been gaining momentum since the think-tank Friends of Cancer Research floated the idea in an October 2015 op-ed. The concept has gained the most traction in oncology; it features in Vice President Biden’s Cancer “Moonshot” initiative, and FDA Commissioner Robert Califf recently said that oncology regulation will be reorganized to create an oncology center of excellence regardless of the fate of the moonshot (“FDA Oncology Center Of Excellence Coming, Moonshot Or Not” — “The Pink Sheet” DAILY, Apr. 20, 2016).

The Imlygic review is an example of one of the pitfalls cited by Friends of Cancer Research: the current FDA center structure “does not allow for the optimal use of [FDA’s] broad spectrum of expertise and can lead activities related to the same disease to be conducted in any number of different parts of the agency” (“FDA Reorganization Advocates Seek Senate Boost For Disease-Oriented Structure” — “The Pink Sheet,” Nov. 30, 2015).

Experience Aiming At Moving Targets

Reviewers in CDER’s Office of Hematology and Oncology Products have become very conversant with melanoma in the past few years as treatment of the disease has been revolutionized by targeted therapies and immunotherapies (“Melanoma Approvals Break New Ground In Immunotherapy” — “The Pink Sheet,” Nov. 2, 2015).

The reviewers in CBER are no less competent, but have had many fewer chances to build subject matter expertise. The Office of Cellular, Tissue and Gene Therapies houses specialized knowledge about the production and quality of biologic products, but lacks the storehouse of experience specific to melanoma that has built up in CDER.

The argument for combining oncology product reviews into one center is one about efficiency, not ability. The CBER staff who reviewed Imlygic were as comprehensive and thoughtful as their counterparts at CDER, but CDER staff would probably not have needed to prepare the elegant and extensive appendix to the clinical review of Imlygic that summarizes the data for Yervoy, Zelboraf, Tafinlar, Mekinist, Opdivo and Keytruda (see timeline, “Imlygic Clinical Development Timeline” — “The Pink Sheet,” Apr. 25, 2016).

Imlygic’s review was complicated by the tremendous change in the medical management of melanoma caused by those approvals (see related story, “Patient Voices Swayed FDA’s Imlygic Review Team” — “The Pink Sheet,” Apr. 25, 2016). Again, the CBER reviewers were more than capable of navigating the regulatory complexities that accompany a fast-evolving space, but CDER has specific experience with such situations that could inform and potentially improve decision-making.

The prostate cancer field underwent a similar upheaval, for example, when the introduction of Xtandi, Zytiga and Jevtana between 2010 and 2013 changed the baseline for what an acceptable comparator and an acceptable clinical benefit could be (“Accelerated Evolution Of Prostate Cancer Therapy Shaped Xtandi Review” — Pharmaceutical Approvals Monthly, December 2012).…