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Pink Sheet – Genentech’s Xeloda Is First Label Updated Under OCE’s ‘Project Renewal’

Pink Sheet – Genentech’s Xeloda Is First Label Updated Under OCE’s ‘Project Renewal’

The FDA’s Oncology Center of Excellence has completed the first “Project Renewal” update to the labeling of an older generic cancer drug with additional indications and dosing regimens for Genentech, Inc.’s Xeloda (capecitabine).

In 2018, officials began discussing the need to update the labeling of older, commonly prescribed oncology drugs to ensure they reflect current practice. The initial goal was to update five labels per year. In 2020, OCE said it had commenced work on the first two labels. (Also see “US FDA Still Seeking Sponsor Cooperation For Oncology Label Updates” – Pink Sheet, 20 Feb, 2020.)

The length of time it took to complete the first labeling update suggests that the process was not as straightforward as the agency first imagined. That is likely due to the inherent challenges with the first oncologic to go through Project Renewal – and the thorny legal issues that were undoubtably involved. (See sidebar for story.)

Xeloda (and generic) labeling now has eight new or revised indications, including the treatment of Stage III colon cancer, locally advanced rectal cancer, colorectal cancer and metastatic gastric cancer, in addition to amended dosing information and new warnings/precautions. (See table below.)

Like all products targeted under Project Renewal, the new uses have long been considered standard of care but the label has been “frozen” in time since the approval of Xeloda generics.

In making the labeling changes, OCE engaged a multi-disciplinary team of external oncology experts, clinical fellows in training and early-career scientists to review the published literature and “gain first-hand experience in the selection, curation, and evaluation of evidence,” the agency said. Those findings are then independently reviewed by the FDA to ensure that the revised labeling provides adequate directions for use.

While Xeloda is the first official labeling change under Project Renewal, OCE has being engaging in label reviews and refining the process along the way. In 2021, OCE evaluated over 25 existing indications and potential off-label uses for three oncology drugs, according to OCE’s annual report.

Education is a big component of the program: last year, OCE “fostered educational experiences” for 12 oncologists and seven hematology/oncology fellows.

Spurred By Friends Of Cancer Research

The approach underlying Project Renewal was first proposed by Friends of Cancer Research as a way for FDA to proactively update longstanding generic labeling to ensure the information is clinically meaningful and scientifically up to date. Once a drug goes generic, the brand name manufacturer has no incentive to continue to update the label, thus the generic labeling cannot be updated either. (Also see “Labeling Updates For Old Drugs Could Be Faster Under Streamlining Proposal” – Pink Sheet, 28 Nov, 2017.)

The idea got the attention of then-Center for Drug Evaluation and Research director Janet Woodcock, who appeared at a FOCR-sponsored briefing on Capitol Hill. She acknowledged that while the FDA night be able to change labels “around the edges” (like a new safety finding), making major changes to labeling for an off-patent drug was, at the time, outside the FDA’s legal authority.  (Also see “US FDA’s Label Updating Effort Needs Legislation To Impact Generics” – Pink Sheet, 20 Mar, 2018.)

FOCR published a white paper in the hopes of encouraging legislation.

In late 2020, the Making Objective Drug Evidence Revisions for New (MODERN) Labeling Act provided a regulatory framework for the FDA to update the labeling of generic products. MODERN created a pathway for updating old drug labels for new conditions of use once the reference listed drug has been withdrawn.

The measure, as a standalone bill, passed the House but did not see action in the Senate.  (Also see “House Bills Would Close Orphan Exclusivity ‘Loophole’ And Thaw ‘Frozen’ Generic Labeling” – Pink Sheet, 18 Nov, 2020.)

However, its provisions were incorporated into the Consolidated Appropriations Act of 2021, and OCE uses that authority in partnership with the Office of Generic Drugs for Project Renewal.