Drugs with potential safety concerns could benefit from demonstrating an efficacy advantage over other agents in the same class, FDA Center for Drug Evaluation & Research Office of Medical Policy Director Robert Temple suggested June 28.

Decisions regarding whether agents such as COX-2 inhibitors should be on the market despite safety risks "would be a lot easier if you really could prove that there were these individual variations," Temple said at the Drug Information Association's annual meeting in Washington, D.C.

Pfizer is interested in returning Bextra (valdecoxib) to the market after pulling the product at FDA's request in April (¹ [A#00670210020], p. 26). Merck also is holding out hope that Vioxx (rofecoxib) could be re-introduced (² Also see "Celebrex Should Stay On Market, FDA Panel Says, But Splits On Vioxx, Bextra" - Pink Sheet, 21 February, 2005., p. 3).

Temple, who stressed the value of comparative studies within drug classes during two separate sessions at the DIA conference, noted that physicians have asserted some patients only respond to a specific COX-2 inhibitor and, therefore, the agency should be wary of keeping any member of the class off the market.

"All the arthritis doctors in the room said, 'well, some people respond to one, other people respond to another,'" Temple said, referring to the joint Arthritis Drugs and Drug Safety & Risk Management Advisory Committee meeting in February (³ Also see "Bextra, Vioxx Require Stronger Warnings, Additional Study, Cmte. Finds" - Pink Sheet, 28 February, 2005., p. 9).

Temple acknowledged that "everybody believes" that "some people respond to one NSAID and not another." However, clinical evidence has not demonstrated differences in efficacy - as opposed to risk profiles - among classes of drugs such as the COX-2s, he said.

"The amount of data that supports that in a rigorous way is, as near as I can tell, zero," Temple said. "The dogma that all people respond differently to drugs in a class has no support."

"It's not that I disbelieve" assertions regarding efficacy differences, he said, "it's that I'm skeptical because...these are uncontrolled anecdotal reports that may or may not be true."

Temple also cited antidepressants as a category in which differences have not been substantiated with strong data. "It may be true of antidepressants; it may be true for lots of things," he said, adding that such claims are "very easy to study."

It is in a company's interests to perform comparative studies, Temple said. "What a great thing to be able to promote," he noted.

Yet, few drug manufacturers test their products against in-class competitors, Temple said. "We never see those unless it's required for approval."

During one of the DIA sessions, the FDAer acknowledged concerns about the introduction of "follow-on" successor brand drugs to head off competition from generics.

He specifically cited AstraZeneca's proton pump inhibitor Nexium (esomeprazole) and its "identical" predecessor Prilosec (omeprazole). Nexium "is one of people's horrible examples of how a generic drug is replaced with the cost of a prescription drug," Temple said.

However, his remarks also suggested that a company's desire to market a follow-on product can produce a beneficial result. In this case, AstraZeneca's interest in marketing a branded successor to Prilosec appears to have resulted in a more optimal dose, he conceded.

"They studied 40 mg of their drug versus 20 mg of omeprazole, and they did better, which means they finally got the dose right," Temple said.

Therefore, "you could say that the desire to carve a niche out is useful," he remarked. "The desire to get your place in the sun sometimes has been extremely beneficial to us."

Temple's comments are the latest signal that FDA is interested in seeing more intra-category efficacy comparisons.

During a recent Cardiovascular & Renal Drugs Advisory Committee meeting, he noted that class labeling is perceived as discouraging manufacturers from conducting further studies of their drugs (⁴ Also see "Hypertension Rx Labels Should Include Product-Specific CV Data – Cmte." - Pink Sheet, 20 June, 2005., p. 7).

Intra-Class Comparisons Could Help Drugs With Safety Issues – FDA’s Temple

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