FDA Encourages Supplements for Oncology Drug

One way to reduce off-label prescribing of treatments for cancer and other conditions is for manufacturers to test additional indications and file supplemental applications to add those uses to approved labeling. The problem is that the testing and approval process for supplements takes a lot of time and money. And formal approval of new uses often is less critical in oncology where off-label prescribing is the norm.

Still, an efficient way to expand labels would be helpful to sponsors in gaining reimbursement for new treatment options, as well as to assure regulators and prescribers that added indications are safe and effective. To this end, FDA’s Office of Hematology and Oncology Products (OHOP) is testing a “streamlined review” process that could be much faster and less costly for certain therapies. Under a pilot program, FDA is reviewing only summary documents and clinical study reports supporting an added indication, but not detailed individual patient datasets from clinical trials. The goal is to identify components of supplements that “may be unnecessary or duplicative” to the known existing clinical and post-marketing safety data for such products, says OHOP acting deputy director Paul Kleutz.

This abbreviated review approach for certain oncology supplements, initially termed “summary review,” was discussed by experts from FDA and industry at the November 2014 conference on clinical cancer research sponsored by the Friends of Cancer Research (FOCR) and the Brookings Institution. Eligibility for summary review would be limited to products that were approved initially with large safety databases and have experienced no notable new safety signals; clear, objective primary endpoints and a robust effect and clear risk-benefit to patients are plusses, Kleutz explained. Summary, or streamlined, review would not be offered to therapies approved under accelerated approval, with novel endpoints, that raise risk concerns or are part of novel drug combinations.

The gains could be important, as faster review times may encourage sponsors to submit supplements, rather than rely on off-label use. Tatiana Prowell of OHOP’s Division of Oncology Products recalled at the FOCR conference that her office approved an Avastin supplement to treat cervical cancer in less than 4 months due to its strong track record for efficacy and well-characterized toxicity profile. But the current supplement review process often involves months to justify approval; “it’s the tail wagging the dog,” Prowell commented. It wastes FDA resources, she noted, at a time when there are many vacancies in the review staff. 

In addition to simplifying the supplement filing process, Lauri Strawn of Pfizer agreed that the “summary” approach would enable sponsors to educate physicians about the added indication, instead of relying on compendial listings. One concern for pharma companies, Strawn added, is that FDA maintains the right to review raw data if needed; thus sponsors need to have detailed patient data on hand in case FDA reviewers pose questions, which greatly reduces potential savings.

European regulators supports FDA’s initiative, as the European Medicines Agency already relies on summary data to support application approvals, explained EMA biostatistician Andrew Thomson. But authorities can request to re-analyze data in certain high-risk situations.

FDA hopes that this streamlined review approach will lead to an increase in supplemental applications, which would widen the availability of approved FDA cancer drugs to patients, Kleutz says. He noted at the November FOCR conference that adopting  streamlined reviews will require “a major culture shift” for OHOP reviewers, and that FDA will need methods to ensure data integrity and to detect any fraud.