Originally published Sept. 12.
By Turna Ray
The US Food and Drug Administration this week announced reforms to its Office of Oncology Drug Products that should improve the group's ability to review marketing applications for pharmacogenomically guided cancer drugs, according to an agency spokesperson.
As part of the reorganization, the Center for Drug Evaluation and Research's OODP has been renamed the Office of Hematology and Oncology Products and has four divisions rather than three. The three prior divisions — the Division of Hematology Products, the Division of Drug Oncology Products, and the Division of Biologic Oncology Products — are now compartmentalized into four new sections: the DHP, the Division of Oncology Products 1, the Division of Oncology Products 2, and the Division of Hematology Oncology Toxicology.
Through these new changes the agency hopes to bring more clarity to the regulatory requirements of bringing new cancer drugs to market. "As the practice of oncology and the treatments being developed for these diseases have become more complex, we've recognized the need and importance of taking a more disease-specific review approach to these therapies," Richard Pazdur, director of the newly restructured OHOP, said in a statement. Pazdur was director of the OODP prior to the restructuring.
The changes to the FDA's oncology drug reviews section come as the agency is increasingly encouraging the incorporation of molecular biomarkers in drug development, a strategy most readily employed in cancer drugs. Recently, the FDA approved two pharmacogenomically targeted cancer drugs — Roche/Plexxikon's Zelboraf for BRAF-mutated melanoma and Pfizer's Xalkori for ALK-positive non-small cell lung cancer — well ahead of its own review deadlines (PGx Reporter 9/7/2011).
"Under the new office structure, the agency anticipates greater clarity and more transparent interactions with companies about the requirements to bring cancer treatments to market," CDER director Janet Woodcock said in a statement. "We don't expect these changes to slow down pending applications, in fact, we expect to see greater efficiencies that will better support our work to get cancer treatments to patients."
Within the reorganization, DOP1 and DOP2 will review application for drugs that treat solid tumors. DOP1 will review drugs that treat breast, gynecologic, genitourinary, and non-hemotologic cancers. DOP2 will focus on gastrointestinal, lung, and head and neck cancers, as well as neuro-oncology, rare cancers, pediatric solid tumors, melanomas, and sarcomas.
DHOT will review nonclinical pharmacology and toxicology elements of cancer drugs. DHP will continue to review hematology therapies for benign disorders and malignancies.
Robert Justice, previous director of DDOP, will lead DOP1; Patricia Keegan, formerly director of the Division of Biologic Oncology Products, will take charge of DOP2; Ann Farrell will remain as director of DHP; and John Leighton, a pharmacology and toxicology reviewer of oncology drugs, has been appointed to oversee DHOT.
An FDA spokesperson explained to PGx Reporter that the creation of DOP1 and DOP2, in particular, should help advance personalized oncology products by engaging agency experts around specific disease areas. This "will allow them to also focus on the latest advances of biomarker development for a particular disease," the agency spokesperson said.
"Also, we anticipate greater consistency on the direction and advice regarding biomarker development that the agency provides to sponsors when working in conjunction with [the Center for Devices and Radiological Health] since specific disease areas will be in one division headed by one division director," the spokesperson added.
The change from OODP to OHOP is occurring during a period of transformation at the FDA as a whole. Commissioner Margaret Hamburg recently made management changes across the agency's various centers. Among the newly appointed officials, Hamburg picked Steven Spielberg, former dean of Dartmouth Medical School and director of the Center for Personalized Medicine and Therapeutic Innovation at Children’s Mercy Hospital in Kansas City, as the Deputy Commissioner for Medical Products and Tobacco (PGx Reporter 7/20/2011). The agency has also recently elucidated its plans to incorporate regulatory science into its review procedures to bring more consistency and improve the agency's oversight capabilities (PGx Reporter 10/6/2010).
The restructuring of OODP also follows a particularly contentious public hearing on the agency's decision to revoke approval for Genentech's Avastin as a treatment for metastatic breast cancer (PGx Reporter 6/29/2011).
Although Genentech asserted that it met the agency's evidentiary threshold to maintain approval of the drug for use in breast cancer, the FDA argued that the treatment should be removed from the market for that indication as its effectiveness did not justify the adverse reactions it caused in some patients. In its bid to keep the drug on the market, Genentech proposed conducting a final validation study in which it would try to identify a best responder population for Avastin using a biomarker strategy.
At the public hearing in June, the FDA did not appear swayed by this strategy, and noted that none of the data published to date suggested that such a biomarker strategy would prove Avastin provided substantial benefit in a subset of breast cancer patients. Although the FDA hasn't yet issued its final decision regarding Avastin, Genentech last month requested that the agency maintain the drug as an option for patients with aggressive disease and limited treatment options — a subset of patients that could include women with a molecularly distinct, triple-negative form of the disease (PGx Reporter 8/17/2011).
Avastin is already approved as a treatment for metastatic colorectal cancer, non-small cell lung cancer, and glioblastoma.
The FDA spokesperson said this week that the agency will hold a series of meetings to discuss how to address drugs targeting biomarkers across multiple cancer disease types. "Where pharmacogenomic markers are targeted across multiple disease groups and divisions, there will be an opportunity to discuss the opinions of each division at OHOP meetings to come to a consensus," the spokesperson said.
Have topics you'd like to see covered in Pharmacogenomics Reporter? Contact the editor at tray [at] genomeweb [.] com.