Immunex Decision On Continuing Enbrel CHF Program Awaits Data Analysis

Immunex' decision on whether to continue development of Enbrel for congestive heart failure awaits a more complete analysis of the data from two halted pivotal trials.

Immunex discontinued two Phase II/III trials of Enbrel (etanercept) for the treatment of CHF following a data safety monitoring board's recommendation March 22 that the studies "are unlikely to reach statistical significance of the efficacy endpoints," Immunex Chief Operating Officer Peggy Phillips told a March 22 conference call to discuss the trial results.

Immunex will have a better understanding of the data set in a couple of months, the company said. The trials will not close until the end of the year due to a time lag for data collection.

"Over the coming months we will collect and assess the complete data set internally and with our advisors. At this point we have seen only the top line data provided from the monitoring board's analysis," Phillips said.

The primary clinical endpoint for each of the trials was improvement in a clinical composite score at six months, including New York Heart Association Class rating, patient's global assessment, hospitalization and death. The primary endpoint for the two trials combined was morbidity and mortality.

In the U.S. Enbrel study, Immunex randomized 925 patients who were on background therapy, such as beta blockers or ACE inhibitors, to either 25 mg twice-a-week etanercept or placebo. The second study was being conducted in Europe by Wyeth-Ayerst. It randomized 1,150 patients on background therapy to either 25 mg Enbrel once or twice a week or placebo.

Trial subjects were primarily Class III patients and had heart failure symptoms for more than three months prior to enrollment in the trial, Immunex said. Enrollment was completed in January and results from the trials were expected by late 2001 or early in 2002.

"About two-thirds of the patients have had a six-month evaluation in the trial at this point," Immunex Senior VP-Clinical Development Leslie Garrison, MD, said. Although the six-month endpoint was the clinical composite, "the data that was analyzed was also looking at morbidity and mortality for the entire trial," she said.

Since patients on the discontinued trials will no longer receive Enbrel, more of the drug could be available for rheumatoid arthritis patients in the Enbrel Enrollment Program, the company said.

"We will be assessing what drug might be available for sale," Phillips said. "It will be our effort to re-label product as much out into the commercial market place as possible."

Enrollment in the Enbrel program for RA patients has reached 76,000, the company said. "We had probably as many as five to ten thousand out of that big number who were inactive as they were going through different parts of the process," Phillips said. About 2,000 patients are on the waiting list, she added.

Immunex' Rhode Island facility is on target to manufacture at full capacity by summer 2002, the company said, adding that the plant has the capacity to produce $750 mil. worth of Enbrel, bringing the total supply of Enbrel next year to $1.5 bil. Immunex anticipates stockpiling Enbrel from the facility starting next year.

The company has begun equipment validation at the plant and expects to finish by mid-year. Production of test batches could begin in the fall. Immunex management agreed with analyst projections that test batch production could take three months, collection of data following production two months, and the FDA approval process four months.

Immunex is looking at a Phase B plan to expand production at the Rhode Island plant in the next four to five years.

The company expects to file a supplemental BLA for Enbrel in psoriatic arthritis by mid-2001. A 205-patient Phase III study for the indication achieved its primary endpoint as defined by the American College of Rheumatology-20 composite score, the company said.

Enbrel is also in Phase II for treatment of psoriasis, Phase II for rheumatological disease and Phase III for Wegener's disease, Immunex said.

A Phase II trial for Immunex' soluble IL-4 receptor Nuvance in steroid-dependent asthma patients is also ongoing, with results expected in the third quarter. Two completed Phase II studies in asthma patients did not show any improvement in opening lung airways over a four-week period.