Monday, August 20, 2001
As inhibitors of pro-inflammatory cytokines take center stage
in treating rheumatoid arthritis, they continue to raise safety questions, a
fact perhaps not surprising given the broad importance of the pathways they
work in. These biologics for RA have the potential to act on other body systems,
such as the immune and nervous systems.
In addition, very little is known about the potential interactions
of these treatments, which so far hasn't been an issue since the two approved
products, Enbrel etanercept from Immunex Corp. and Remicade infliximab from
the Centocor division of Johnson & Johnson, both target TNF.
But if the FDA goes along with last Thursday's recommendation
of its Arthritis Advisory Committee to approve Amgen Inc.'s Kineret anakinra
IL-1 receptor antagonist, the question of how these biologics interact is bound
to come up.
Surprisingly, however, even after probing the issue in its
Kineret deliberations, the panel on Friday passed up another opportunity to
examine the issue more deeply.
Thursday's meeting demonstrated clearly the challenges the
agency faces in staying ahead of the changing therapeutic picture for RA. With
two biologics on the market, FDA has given AMGN more hoops to jump through in
its quest for approval of Kineret.
And while Kineret met its prespecified efficacy goals, AMGN's
answers to some of the agency's requests gave the committee pause, making it
appear that some members might like to see FDA raise its approval bar for biologic
agents that are not first to market.
On Thursday, Roger Perlmutter, AMGN's executive vice president of R&D, described Kineret's activity in terms of its place in the cytokine lexicon. The recombinant interleukin-1 receptor antagonist binds and occupies IL-1 receptors but blocks their activation by preventing assembly of the receptor complex.