By Debbie Strickland

With CD4 cell depletion occurring in about one-third of patients, IDEC Pharmaceuticals Corp. and SmithKline Beecham plc have suspended the rheumatoid arthritis clinical trial of IDEC-CE9.1/SB-210396, one of IDEC's primatized monoclonal antibodies.

"While there have been no reports of side effects related to lower CD4 counts in this trial, the companies have decided to place a hold on the current clinical trials pending a thorough review and analysis of the data," IDEC and SmithKline Beecham said in a joint statement.

"We're taking what we think is the most conservative approach until we understand what is going on," Connie Matsui, IDEC's vice president for planning and resource development, told BioWorld Today.

One of the criteria for trial participation was a minimum initial CD4 cell count of 400 per microliter.

"We're seeing a proportion of people dropping to 250 or below," Matsui said.

Genetically engineered from monkey and human antibody components, IDEC-CE9.1 coats the surface of cells that have the CD4 receptor, blocking the action of that receptor, which is involved in T cell immune response. In many autoimmune diseases -- rheumatoid arthritis, for example -- overactive T cells can drive the immune system to attack and destroy healthy tissues.

In the now-stalled Phase III trial, 35 of 103 patients' CD4 cell count fell during the first month of treatment, more than triple the rate observed in the Phase II trial at the same point, when 10 of 136 manifested CD4 cell reduction. Five of those 10 Phase II patients bounced back to normal CD4 cell levels within three months.

As part of an ongoing follow-up, the companies plan to monitor the duration of CD4 cell depletion in Phase III patients.

London-based SmithKline Beecham and IDEC, of San Diego, also will assess efficacy for those patients who have completed the initial part of the Phase III trial. The Phase II study demonstrated significant clinical improvement in the signs and symptoms of rheumatoid arthritis.

The companies said they were "uncertain" of the cause of the higher frequency of CD4 suppression in Phase III. Possible sources include patient variables and shifts in dosing and manufacturing.

Some of the changes between the trials were substantial. The maximum Phase III dose was 240 mg once a week, while the highest Phase II dose was 140 mg twice a week.

In the meantime, the companies' collaborative agreement remains in effect. That agreement, worth up to $60 million (the bulk of it already paid) to IDEC, also covers what Matsui called "a back-up antibody," IDEC-151/SB-217969, a second-generation anti-CD4 rheumatoid arthritis treatment now in a Phase IIa trial.

"If there were not a reasonable back-up in the pipeline, we would see [the Phase III suspension] as pretty discouraging news," Matsui said.

There are no plans currently to re-evaluate the collaborative agreement that covers both products, said Richard Koenig, a spokesman for SmithKline Beecham.

"What we're evaluating are the data of this particular Phase III trial and this particular antibody," he said.

In their statement, the companies said they remain "committed to the development of anti-CD4 approaches to the treatment of rheumatoid arthritis and other autoimmune diseases."

As for the impact of the clinical stall on IDEC, "it's a blow," said analyst David Webber, of SBC Warburg & Co. Inc., in New York. "But it's not disastrous to the company in my view due to the breadth of the company's product portfolio. This is not a one-product biotech company."

He noted that IDEC's lead drug, Rituxan, or IDEC-C2B8 (rituximab), codeveloped with Genentech Inc., of South San Francisco, appears likely to receive FDA approval this year. An FDA advisory panel will discuss the treatment for non-Hodgkin's lymphoma July 25. It would be IDEC's first marketed drug.

Webber also applauded the company's strategy of having a related back-up drug waiting in the wings behind IDEC-CE9.1.

"One of the things I like about IDEC is that it tries, to the extent possible, to carry out drug development like a big company," Webber said. "One thing all the big pharma companies do is have a back-up molecule."

In research notes issued after the announcement of the trial suspension, he maintained a "buy" recommendation, but using a "worst case scenario" model that excludes possible earnings from IDEC-CE9.1, he lowered the 12-month share price target to $33 from $46.

IDEC (NASDAQ:IDPH) stock closed at $23.25, down $2.625. *