By Jim Shrine
Immunex Corp. and its partner began a Phase II/III trial of Enbrel, in a study representing a new approach to treating patients with chronic heart failure.
The drug, recently approved for treating patients with moderately to severely active rheumatoid arthritis (RA), works by binding to tumor necrosis factor (TNF) and preventing it from interacting with cell-surface receptors in the heart and circulatory system. Immunex research and early studies have shown association between elevated TNF levels and chronic heart failure.
"This is an entirely new approach in trying to help people with this disease," said Tim Warner, director of corporate communications at Immunex. "The early studies have established a foundation upon which our two companies have decided to move forward with a very aggressive, global clinical development program."
Immunex, of Seattle, is running the studies with partner Wyeth-Ayerst Laboratories, a division of Madison, N.J.-based American Home Products Corp. AHP owns about 54 percent of Immunex.
The study will include 900 patients in the U.S. and 900 in Europe and Australia in trials called RENAISSANCE (which stands for Randomized Enbrel North American Strategy to Study Antagonism of Cytokines) and RECOVER (which stands for Research into Enbrel: Cytokine Antagonist in Ventricular Dysfunction), respectively. They were designed after a 47-patient Phase I study suggested Enbrel resulted in improvements in various quality-of-life endpoints. It also was well tolerated.
Results from the Phase I study were presented at this week's American College of Cardiology (ACC) meeting in New Orleans.
Enbrel will be studied now in double-blind, placebo-controlled Phase II/III trials, with main endpoints being clinical composite scores six months after treatment and measures of morbidity/mortality. Specific doses were not disclosed.
Phase II/III Data Could Come In First Half Of 2001
"We think we will have results as early as the first half of 2001," said Pam Robe, a communications specialist at Immunex. "The two trials will be analyzed together for a morbidity/mortality endpoint based on clinical composite scores at six months."
She said the composite endpoints taken from the separate trials make up be the Phase II portion of the trial, with results from all 1,800 patients combined to power the Phase III results.
The composite scores will be based on measurements such as patient global evaluations and New York Health Assessment classifications, in which a "I" ranking shows no limitation of physical activity and "IV" measures the inability to carry on activities without discomfort.
Immunex said about 5 million Americans suffer from chronic heart failure, which is a form of heart disease resulting from damage by conditions such as high blood pressure, a heart attack, poor blood supply, atherosclerosis and defective heart valves. They render the heart inefficient.
Immunex and Wyeth-Ayerst have the same relationship for Enbrel in this indication as they do in RA. They would co-promote the product in North America, with Immunex recording sales and getting more than half of the profits from those sales. Their Enbrel deal includes all indications other than oncology.
Enbrel Sales Of About $40M Expected In First Quarter
In RA, Immunex has been guiding investors to expect about $40 million in Enbrel sales in the first quarter.
The moderate and severe RA cases for which the product was approved in November address about 20 percent to 32 percent of the 2.5 million Americans with RA, Warner said. Immunex expects to complete a Phase III trial in early-stage RA - which represents the bulk of the market - in the second quarter, he said. In addition, the company filed for approval in juvenile diabetes in November.
Enbrel also is being a tested in a variety of investigator-sponsored studies for inflammatory conditions, such as psoriatic arthritis and Crohn's disease.
'The early trials in chronic heart failure pointed us [toward the more-extensive heart failure study]," Warner said. "There clearly is a commitment to developing this drug for this potential indication, and we continue to look at other potential indications as well.
"It's our 'product with a pipeline,'" he said.
Immunex's stock (NADAQ:IMNX) gained $3.25 Monday to close at $156.75.
In other news from the ACC meeting:
* COR Therapeutics Inc., of South San Francisco, said Phase I and early Phase II results from trials of its oral glycoprotein IIb/IIIa inhibitor, cromafiban, showed it had high affinity and specificity for the target. Inhibition of platelet aggregation was shown to be dose- and concentration-dependent. Data also suggest once-daily dosing would be sufficient.
* Chiron Corp., of Emeryville, Calif., said Phase I data will be presented Wednesday from its rFGF-2 product to treat coronary artery disease. The data indicated fibroblast growth factor was safe and well tolerated across a number of doses, and they support moving into Phase II, where improved blood flow to the heart will be evaluated.