By Lisa Seachrist

Washington Editor

Riding the wave initiated by Immunex Corp.'s Enbrel and more recently Centocor Inc.'s Remicade, biologics continue to offer the most promising potential therapeutic options for rheumatoid arthritis (RA).

Biologic-based drugs garnered intense interest amongst clinicians, researchers and investors at the American College of Rheumatology's 63rd Annual Scientific Meeting in Boston this week. The buzz surrounded not only approved products such as Enbrel and Remicade, which got FDA approval as a rheumatoid arthritis treatment just days before the meeting started, but therapeutics in all stages of clinical development.

"This is a trend that started in full force last year," said Eric Schmidt, vice president of SG Cowen Securities in New York. "We're getting a little bit spoiled in this field. One of the themes of this meeting is that we continue to make progress in this field with biologic drugs that have a significant impact on disease and the patient's quality of life."

Schmidt likened the progress to date to the HIV field when protease inhibitors came to the forefront - the new products are holding the promise not to cure RA, but to significantly decrease the pain and disability associated with the disease.

While Seattle-based Immunex presented data showing its protein inhibitor of tumor necrosis factor, Enbrel, was effective in more than 70 percent of children suffering from severe, longstanding, rheumatoid arthritis, Thousand Oaks, Calif.-based Amgen Inc. presented the Phase II data from its interleukin-1 receptor antagonist, Kineret. Kineret is a recombinant form of the cytokine IL-1ra, which selectively blocks the effects of IL-1, a cytokine released as part of the disease process in rheumatoid arthritis.

Amgen Plans BLA In Near Term

The 419-patient study showed that 42 percent of patients receiving a Kineret injection once a day when combined with methotrexate achieved a meaningful clinical response compared to just 23 percent of the patients who received placebo injections. In addition, Kineret didn't increase the chance of infections like the anti-TNF drugs Enbrel and Remicade.

"We'll be filing a biologics application for Kineret in the next few months," Amgen spokesman David Kaye said. "After discussions with the FDA, we've decided to go ahead and file our Phase II data and continue to conduct safety studies."

The company also presented Phase I data of its anti-TNF drug, sTNF-RI. That study showed the drug was safe and well tolerated by people with moderate to severe disease. The company is currently conducting a Phase II study of this drug. Ultimately, Kaye said, the company will investigate how the two drugs could be used in combination.

The Immune Response Corp., of Carlsbad, Calif., presented data from a Phase II clinical study of its therapeutic vaccines, IR501 and IR701. The vaccines are based on the premise that the autoreactive T cells playing a primary role in the joint destruction of RA have unique receptor proteins. The vaccines are aimed at these receptors.

"This is designed to treat the disease in addition to the symptoms," said Creighton Lawhead, vice president of commercial affairs at Immune Response Corp. "What we are doing is shutting down the harmful T cells that are causing tissue damage."

The vaccine trial showed a significant improvement for disease signs and symptoms among patients who received dosages of the vaccine compared to placebo. In addition, the study showed early-stage patients received a greater benefit.

"Previous studies have shown the vaccines work in moderate to severe patients, which indicates they may be effective for a wide range of patients," Lawhead said. "The key appears to be priming patients. We will most likely look at monthly injections in future trials."

Lawhead said the company is in discussions with interested pharmaceutical partners to fund further development of the vaccines. Until those negotiations are completed, he doesn't expect any pivotal trials to begin. The company also is developing therapeutic vaccines to treat psoriasis and multiple sclerosis.

Alexion, Isis Present Encouraging Data

Alexion Pharmaceuticals Inc., of New Haven, Conn., presented intriguing results from a Phase I study of its anti-inflammatory complement inhibitor, 5G1.1. The complement cascade is a series of proteins that serves as the first response to foreign invaders and infection. Alexion's product targets the C5 protein, which can lead to the activation of T cells and the release of damaging cytokines such as TNF and IL-1.

The Phase I study tested a single dose of the drug in 42 patients with mild to moderate RA. Fifty percent of the patients receiving the highest dose of the drug showed significant improvement in the signs and symptoms of disease compared to 10 percent of the placebo patients.

Schmidt noted the study was very small, but added, "The mild to moderate patients are a difficult group to show efficacy in. It's an encouraging result."

Alexion has the drug in a Phase II study in RA as well as membranous nephritis patients.

Isis Pharmaceuticals presented data showing its antisense oligonucleotide, ISIS 2303, an inhibitor of ICAM-1 - an intercellular adhesion molecule that is central to the upregulation of the inflammatory system - showed statistically significant improvement of the signs and symptoms of RA compared to placebo. The company, however, won't continue development of this particular drug because it is an intravenous agent. Instead, it is planning to conduct trials of a second-generation, orally active antisense drug for RA.