Bristol-Myers Squibb's proposed pharmacovigilance program for Orencia (abatacept) provides a sufficient level of safety oversight, members of FDA's Arthritis Drugs Advisory Committee said in recommending approval of the rheumatoid arthritis therapy Sept. 6.

"I, personally, am very comforted by the pharmacovigilance plan. I think that that will provide us with additional information," committee chair Allan Gibofsky (Cornell University) said.

Bristol's proposed pharmacovigilance program for Orencia includes a cohort study using UnitedHealthcare claims data and an observational study comparing 5,000 Orencia patients with 15,000 patients receiving other RA therapies.

The panel voted unanimously in favor of recommending approval of Orencia.

[Editor's Note: To ¹ watch a webcast or order a video/DVD of this meeting, visit FDAAdvisoryCommittee.com.]

In briefing documents for the meeting, FDA expressed concern about an increased risk of serious infections and a potential risk of malignancy with the T-cell costimulation modulator (² Also see "Bristol Abatacept Infection, Malignancy Risk To Be Considered By Advisory Committee" - Pink Sheet, 2 September, 2005.).

Committee consultant David Felson (Boston University) said abatacept's "safety profile seems like the other TNF inhibitors that we know reasonably well." Abatacept and TNF inhibitors are both immunosuppressants.

Three TNF inhibitors are currently marketed: Abbott's Humira , Amgen/Wyeth's Enbrel and J&J's Remicade .

Infection, malignancy risk and auto-immune related diseases such as type 1 diabetes are the most serious safety concerns for abatacept, committee members said.

Committee members agreed that abatacept should not be coadministered with biologic RA therapies, including TNF inhibitors. "The sponsor's plan to advise against use with biologics is a wonderful idea," Felson said.

In a Phase III safety study, serious infection rates for patients receiving abatacept and a biologic were triple those of patients receiving placebo and a biologic (³ Also see "Bristol's Abatacept Shows Elevated Infection Risk In Phase III Safety Study" - Pink Sheet, 9 June, 2005.).

Committee members agreed that the agent was effective at reducing RA signs and symptoms, improving physical function and inhibiting the progression of structural damage.

"The efficacy of this compound is quite well established - there is no real question about that," committee consultant Michael Holers (University of Colorado Health Sciences Center) said.

In pivotal trials, abatacept was associated with a statistically significant reduction in the signs and symptoms of patients inadequately responding to methotrexate or TNF inhibitors (⁴ Also see "Abatacept Launch Will Be Bolstered By Unmet Need In RA Market – Bristol" - Pink Sheet, 17 November, 2004.).

In a release issued after the committee meeting, Bristol announced that FDA extended abatacept's user fee action date 90 days to Dec. 31 (see ⁵ Also see "Will Manufacturing Issues Hobble Abatacept?" - Pink Sheet, 6 September, 2005. ).

- Andrew Kasper

Bristol Orencia Pharmacovigilance Plan Sufficient For Approval, Committee Says

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