By Mary Welch

SmithKline Beecham plc said it will delay starting Phase IIb trials of the anti-CD4 immunotherapy for rheumatoid arthritis that the company is developing with Idec Pharmaceuticals Corp., based on the product profile emerging from recently finished Phase I/II trials and an open-label extension trial.

"Nothing bad happened in the trials," said Mike Houldin, spokesman for London-based SmithKline. "We're just carefully reviewing the data and reconsidering strategy. That's all we're saying."

The postponement is the second setback in the $60 million anti-CD4 collaboration, which experienced a Phase III trial failure in 1997.

Bill Rohn, chief operating officer for Idec, of San Diego, said SmithKline's disclosure was a "rather fresh development. We've had a little bit of dialogue going on, and we're getting a major steering committee going the first or second week in January to understand, more in depth, their position. Clearly, something emerged out of the Phase I/II trials that gave them pause. They had planned a fairly aggressive Phase IIb lined up, with about four or five trials and lots of money."

But, he added, SmithKline is "footing the bill now. The short-term financial impact on [Idec] is zero."

IDEC-151/SB-217969 (clenoliximab), a second-generation anti-CD4 treatment, was the collaboration's back-up antibody. The lead primatized monoclonal antibody, IDEC-CE9.1/SB-210396 (keliximab), subject of the halted Phase III trials, is genetically engineered from monkey and human antibody components. It coats the surface of cells that have the CD receptor, blocking the action of that receptor, which is involved in T cell immune responses.

In many autoimmune diseases — rheumatoid arthritis, for instance — overactive T cells can drive the immune system to attack and destroy healthy tissues. (See BioWorld Today, June 25, 1997, p. 1.)

Enbrel, Rituxan Competition May Be Too Stiff

Rohn speculated SmithKline's decision came, in part, from market considerations related to Seattle-based Immunex Corp.'s Enbrel and South San Francisco-based Genentech's Rituxan.

"The efficacy bar has been raised with Enbrel and Rituxan on the market," he said. "Enbrel is self-administered, [and] IDEC-151 is by injection, so they may want to look at ways to spread out the drug so injections are less frequent. Maybe we should consider IDEC-151 in combination with methotrexate. If we're going to enter the ballgame, we want to enter the game to win."

Enbrel (etanercept) is a genetically engineered protein — two molecules of recombinant human tumor necrosis factor (TNF) receptor — that works by binding TNF, thus blocking TNF's interaction with cells that respond to its signal. TNF is found at elevated levels in fluid around the joints of patients with rheumatoid arthritis. Enbrel was approved by the FDA last month. (See BioWorld Today, Nov. 3, 1998, p. 1.)

Rituxan (rituximab) is a chimeric monoclonal antibody aimed at the CD20 antigen found on mature B cells. Approved by the FDA in December 1997, it was developed by Idec and Genentech Inc., of South San Francisco.

The original deal between Idec and SmithKline Beecham for rheumatoid arthritis dates from October 1992, when SmithKline agreed to pay up to $30 million in developing Idec's primatized anti-CD antibody. Since then, the agreement has increased to about $60 million, most of which already has been paid to Idec.

"The only real milestone we have left is upon FDA approval," Rohn said. "We still have a co-promotion agreement, so we still are very interested in its future and success."

SmithKline emphasized the decision is not a fatal one for the drug.

"Nothing is dead," Houldin said. "We're looking at opportunities and possible development re-evaluation. I wish I could say more, but there's going to be a lot of people looking at the data, and I couldn't say when a final decision will be made as to the direction."

The two companies are still investigating the drug in other indications, such as psoriasis and severe asthma.

Idec's stock (NASDAQ:IDPH) closed Wednesday at $44.125, down $2.687. *

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