Many NDAs, BLAs, and INDs for cancer drugs are being reassigned to new review divisions as part of a reorganization of FDA's Office of Oncology Products.

On Sept. 12, the agency unveiled a long-expected reorganization of the Center for Drug Evaluation and Research's Office of Oncology Products, headed by Richard Pazdur. The reorganization is now complete, an FDA spokesperson confirmed.

As expected, Pazdur will remain at the helm of the office, renamed as the Office of Hematology and Oncology Products (OHOP) and his leadership team remains intact, though their coverage areas will change in some cases (Also see "FDA Oncology Products Office Reorganization Keeps Leadership Intact" - Pink Sheet, 26 July, 2010.).

Previously, Pazdur's department had included three sections: the Division of Hematology Products (DHP); the Division of Drug Oncology Products (DDOP); and the Division of Biologic Oncology Products (DBOP).

The new structure includes four divisions, including the DHP, two Divisions of Oncology Products for solid tumors - DOP1 and DOP2- and a newly created Division of Hematology Oncology Toxicology (DHOT), which will focus on the pharmacology and toxicology of cancer therapies. Each division will have roughly the same number of reviewers, according to the agency spokesperson.

Restructuring Based On Disease Type

DOP1 includes breast, gynecological and genitourinary diseases. That grouping makes intuitive sense because the diseases are hormonally responsive and often experts share information and work across these areas, commented Grant Williams, an oncologist and formerly a reviewer and deputy director in oncology drugs at FDA.

DOP2 covers reviews of gastrointestinal, lung, neurological, rare diseases, pediatric and melanoma.

Reorganization requires reassignment of current INDs, NDAs and BLAs to the new DOP1 and DOP2 sections (with reassignment based on indication/division), as well as reassignment of applications to DHP, FDA noted in supplementary information for companies.

The agency has provided a list of applications that will be moving to new divisions. Applications that have pending actions will remain in their existing divisions, unless otherwise directed, until they can be reassigned to the appropriate new division.

As for yet-to-be submitted NDAs, BLAs and INDs, these should be directed to the appropriate new division.

"Going forward, OHOP will request new INDs for each primary tumor site being studied," the agency noted.

Restructuring based on disease type had long been expected and is similar to the way most oncology centers in academic institutions are organized, with experts in particular diseases.

The changes could help bring uniformity and expert attention to the review process, at a time when there are many subtleties in terms of appropriate endpoints, depending on the tumor type, commented Williams, who now runs a consulting business in drug development and approvals.

The restructuring also could make it easier to hire staff, because the organization will be structured more like academia and will offer potential personnel a more attractive career opportunity to be highly specialized within a particular disease type at the agency, Williams commented.

Other recent reorganizations within CDER have focused on anti-infective drugs, rheumatology and medical imaging ([A#0110509005]).

Staff Select Divisions

Commenting previously on the proposed changes previously, Office of New Drugs Director John Jenkins had said that the reorganization would give "staff an opportunity to declare what diseases they are most interested in focusing their attention on" (Also see "Oncology Drug Reviews To Be Restructured As Office Shifts Away From Divisions Organized Around Molecule Size" - Pink Sheet, 12 April, 2010.).

"Office leadership met with office staff to discuss areas of interest and staff were assigned based on experience and expertise," the FDA spokesperson explained.

OHOP has 130 employees, including 55 oncologists and 39 pharmacists, according to the FDA press statement about the reorganization.

The Division of Hematology Products will be continue to be led by Ann Farrell. The DOP1 division will be headed by Robert Justice, formerly head of the Division of Drug Oncology Products. Patricia Keegan, formerly head of the biologicals division, will take charge of DOP2. And John Leighton, formerly associate director of the Office of New Drugs' pharmacology toxicology staff, will be leading the new DHOT.

Aside from the leadership, FDA has not released the particular staff assignments for each division.

Implications For Avastin?

The reorganization also could mean changes in the review divisions of some high-profile applications. For example, Commissioner Margaret Hamburg is considering the future of Roche/Genentech's Avastin (bevacizumab) in metastatic breast cancer after CDER proposed revoking the drug's accelerated approval for the indication in June.

The company has proposed keeping the drug on the market for certain high-risk populations while it develops a confirmatory trial (Also see "Genentech Restricts Population In Last-Ditch Bid To Keep Avastin's Breast Cancer Claim" - Pink Sheet, 5 August, 2011.).

In terms of indication, this drug would now fall under Robert Justice's DOP1 team. Presumably, discussions about a confirmatory trial would be handled by DOP1, though neither FDA nor Genentech could confirm this. Nor is the Avastin BLA number on FDA's list of applications moving to DOP1.

Avastin's BLA had been handled by the biologicals division under Keegan, who is now in charge of DOP2. Keegan had been opposed to the accelerated approval of Avastin in metastatic breast cancer (Also see "Avastin’s Breast Cancer Approval Followed CDER Rift On Efficacy" - Pink Sheet, 30 May, 2011.).

In fact, the official had raised questions about the magnitude of effect in the supporting trials and had favored a "complete response" letter, but she appeared to have been overruled by the clinical reviewer and Pazdur, who initially supported accelerated approval (Also see "Avastin Breast Cancer Approval Memo Comes Back To Haunt FDA’s Pazdur" - Pink Sheet, 18 July, 2011.).

Pazdur, who now appears much more skeptical of Avastin's benefit in breast cancer, will presumably have considerable input in the design of the confirmatory trial regardless of where the application ends up being assigned (Also see "An Avastin Loophole: Hamburg Could Decide To Retain Approval During Confirmatory Trial" - Pink Sheet, 9 May, 2011.).

- Emily Hayes (e.hayes@elsevier.com)

Oncology Drug Applications Migrate As Part Of FDA's Reorganization Of OOP

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