FDA Treads Carefully On Reprints, Citing Taxotere “Carrier,” Not Study

Printing a list of "unsubstantiated" superiority claims for breast cancer drug Taxotere (docetaxel) on the outside of study reprints has earned Sanofi Aventis a citation letter from FDA's Division of Drug Marketing, Advertising and Communications.

In the letter, DDMAC does not take issue with the data included in the reprint itself, but rather with the claims Sanofi made summarizing and interpreting that data in the "professional reprint carrier" - a promotional piece like a folder that holds the reprint - by printing a list of superiority claims for the drug that FDA says were not supported by the enclosed study.

The reprint was from the Journal of Clinical Oncology and distributed at last year's American Society of Clinical Oncology annual meeting. FDA's letter comes just as many firms are likely finalizing their promotional plans for this year's ASCO meeting, which will be held May 28 through June 2 in Orlando, Fla.

FDA's ¹ letter to Sanofi also sets the stage for companies to revisit their approach to reprint distribution in general in light of the change of administrations.

Letter In Accord With Final Guidance

One of FDA's last acts under the Bush administration was to issue a guidance on distribution of off-label reprints that states journal articles should address adequate and well-controlled trials, but that those trials need not meet the same standards that would be required to garner approvals (² (Also see "Off-Label Reprint Guidance: “Definitely Improved,” But Will Waxman Fight On?" - Pink Sheet, 19 Jan, 2009.), p. 31).

Consumer groups and many in Congress greeted the new guidance with howls of protest, calling it a rollback of previous limits on reprints. There has been some speculation that the Obama administration would withdraw the document, but the move against Sanofi suggests that the agency may feel comfortable taking enforcement actions even with the new guidance still in effect.

Sanofi's behavior, in fact, seems to explicitly violate the guidance. Reprinting the less-than-robust trial appears fine, but the guidance is clear that the medical information distributed should "not be marked, highlighted, summarized, or characterized by the manufacturer in any way (except to provide the accompanying disclosures...)."

That the statements were even made on the reprint carrier also appears to have violated the guidance, as the agency also says the reprint should be distributed separately from information that is promotional in nature.

Of course, the question remains how vigorously FDA will enforce these policies, and whether, perhaps, the superiority claims in the carrier drew the agency's ire when a more straightforward summary might have been given a pass.

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Superiority Claims, Failed Statistical Significance

The claims in Sanofi's carrier made reference to the open label, randomized, "TAX 311" study comparing Taxotere to paclitaxel. The study did not meet its primary endpoint of objective response, but Sanofi notes on the reprint carrier Taxotere's superiority in meeting secondary endpoints of time to progression, response duration, and overall survival.

The reprint carrier includes phrases such as "This phase III study demonstrated that docetaxel is superior to paclitaxel in TTP, response duration, and OS"; "Phase III trial demonstrates improved survival for Taxotere vs paclitaxel in metastatic breast cancer"; and "TAX 311: Taxotere demonstrated efficacy benefits vs paclitaxel."

DDMAC states in the letter that "the reference cited in support of these claims ... does not constitute substantial evidence or substantial clinical experience to support these claims and representations because, among other factors, the study failed to demonstrate statistical significance on the primary endpoint and has not been replicated."

Taxotere is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.

- Jamie Hammon ([email protected])