“DDMAC Watch” Challenges FDA Authority Over Sales Reps’ Statements

The Washington Legal Foundation is questioning FDA's legal authority to regulate oral statements by sales representatives.

The foundation's "DDMAC Watch" raised the issue following an FDA ad review division letter that cites a Roche sales rep's oral statements concerning the HIV therapy Fuzeon (enfuvirtide).

The agency may not prohibit Roche from "providing information to physicians about new studies relating to the effectiveness" of Fuzeon's approved indication, ^FDL-1 WLF's July 19 letter to FDA's Division of Drug Marketing, Advertising & Communications said.

"There is, at best, uncertainty surrounding DDMAC's authority to regulate oral statements by a sales representative," WLF said.

"Moreover, DDMAC's practice of evaluating the veracity of drug company statements by comparing them to the FDA-approved labeling, which concededly does not contain all that is known about the drug, raises substantial legal and policy questions."

WLF requests that FDA rescind its July 15 ^FDL-2 ad review division letter, in which the agency said a Roche rep's statements at the November 2004 Interscience Conference on Antimicrobial Agents & Chemotherapy "recommend or suggest uses for Fuzeon that have not been approved by FDA."

FDA's letter asserts that a Roche rep "stated, in word or in substance, that Fuzeon is appropriate for all treatment-experienced patients," thereby broadening the drug's indication.

The product is approved for use in combination with other antiretroviral drugs for treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy, FDA noted.

The Roche rep at the ICAAC meeting also asserted that Fuzeon "confers '100% antiviral activity,' thereby suggesting that: (1) all patients will respond to the drug, and (2) it would be appropriate for a broader range of patients than those for whom it is actually approved," FDA said. The rep also said that "100% of patients are susceptible to Fuzeon," the letter states.

FDA said the Roche rep further claimed that Fuzeon, which is an injectable, is "better than oral HIV drugs." The statement "misleadingly suggests that Fuzeon is an alternative to oral HIV drugs, when in fact it is approved for use in conjunction with such drugs," the agency said.

FDA requests that Roche submit a response by July 29 listing all promotional materials that contain the cited claims and describing a plan for halting their use.

Roche said it is reviewing the letter and will respond within the specified timeframe.

FDA's letter to Roche is not the first time a firm has been cited for statements made by reps at a medical conference. The agency sent a letter to Gilead in 2002 regarding sales reps' statements at ICAAC for the HIV therapy Viread (¹ (Also see "Booth Promotion Compliance Improving, FDA Says; Gilead Viread Cited At ICAAC" - Pink Sheet, 1 Apr, 2002.), p. 4).

In its letter to FDA, WLF said the agency's authority over oral statements by sales representatives is "highly questionable, at best."

FDA's jurisdiction over drug promotion only encompasses print and broadcast media, WLF said. "There is therefore no textual basis for DDMAC's assertion of direct content regulatory authority in this instance."

No court has found an FD&C Act violation based on a sales rep's oral statements, WLF said. "To the contrary: misbranding based solely on oral statements has been expressly rejected."

DDMAC has not issued guidance on oral statements by reps; therefore, "it is inappropriate for DDMAC to issue an untitled letter alleging a misbranding violation based on an oral statement by a single" Roche employee, WLF said.

WLF launched the DDMAC Watch program in June to challenge ad review division letters that the organization believes are legally insufficient or ill-advised (² (Also see "WLF Questions Ad Division Allegations; “DDMAC Watch” Starts With Strattera" - Pink Sheet, 27 Jun, 2005.), p. 21).

Fuzeon was co-developed by Roche and Trimeris; the companies are also collaborating on development of future generations of peptide fusion inhibitors.

Enfuvirtide received accelerated approval in March 2003 and full approval in October 2004.

Early sales of the drug were lower than expected. Many clinical practices were slow to adopt Fuzeon due to the product's route of administration and "incidence of injection site reactions," Trimeris CEO Steven Skolsky said during a July 20 earnings call.

However, the second quarter marked the first profitable quarter in Trimeris' collaboration with Roche, driven largely by Fuzeon sales growth.

Worldwide Fuzeon net sales in the quarter were $53.9 mil, up 48% from the year-ago quarter, Trimeris said. U.S. and Canadian sales were $25.2 mil., up approximately 3% from a year ago and up 8% from the first quarter. All Fuzeon sales are recorded by Roche.

Emerging data on other HIV antiviral drugs, both in development and newly available, are helping to raise Fuzeon's profile as "the foundation of highly active therapy for treatment-experienced patients," Skolsky maintained.

"Our continuing efforts on focused positioning and targeted promotion will reflect this emerging data, and will work synergistically with our focus on alleviating the burden of injection site reactions with alternative delivery systems and ongoing patient and market support initiatives," he said.

Roche and Trimeris' efforts to improve sales have included nationwide advertising and nursing support programs (³ , p. 36).

Roche sales reps are actively promoting the Fuzeon "nursing connections" program, which evolved from an earlier nursing program designed to augment standard Fuzeon training and follow-up, Skolsky said.

Trimeris filed an sNDA in May for Fuzeon administration with the Biojector 2000 needle-free delivery system.

Needle-free administration "represents an important option for patients and health care providers that may enable more patients in need of Fuzeon to start therapy while assisting current Fuzeon patients to remain on therapy," Skolsky maintained.

Trimeris expects a six-month review for the sNDA and is working with Roche to make the B2000 system available in the first half of 2006.