By Debbie Strickland
Among the presenters at this week's American College of Rheumatology science meeting are two biotech firms whose rheumatoid arthritis (RA) drugs achieved positive results in recent clinical trials: Centocor Inc., which presented findings of a Phase II trial of Avakine, and Immunex Corp., which released additional Phase III data on Enbrel.
Centocor, of Malvern, Pa., plans to submit a biologics licensing application by year end for the monoclonal antibody-based therapeutic, formerly known as cA2 (infliximab), which is also under development for Crohn's disease.
Although Centocor said the drug "demonstrated profound, sustained benefits," investors reacted negatively to the data and possibly to results, presented separately at another conference, on the company's anticoagulant product, ReoPro, administered in combination with thrombolytics.
Centocor's stock closed Monday at $43.125, down $9, or 17.3 percent.
"The stock deflated primarily due to two pieces of news which were likely misperceived," said analyst Anthony Butler, of Lehman Bros., in New York.
Investors, he said, may have been overly concerned about possible side effects related to Avakine. However, he added, "No data to date suggest an increase in lymphomas or infectious diseases as a result of Avakine."
Some observers also evidently found data from the ReoPro trial in acute myocardial infarction, also a Phase II study, to be "not as robust as expected," Butler said.
Analysts Say Investors Misunderstood Data
"There's clearly some misperception," he said, calling ReoPro's action "additive" and "synergistic." The ReoPro findings were presented last weekend at the American Heart Association's scientific meeting, in Orlando.
Analysts Tim Wilson and Eric Schmidt, with UBS Securities, in New York, likewise found the ReoPro data encouraging.
"The data showed that ReoPro increased occluded coronary artery flow when added to reduced doses of conventional thrombolytics," they wrote in a report on Centocor.
Both Butler and the UBS analysts continue to recommend Centocor's stock.
"The market was very confused today," said Butler.
In the 26-week Phase II RA trial, 60 to 70 percent of patients receiving 1, 3 or 10 mg/kg of Avakine with methotrexate and 3 or 10 mg/kg of Avakine without methotrexate achieved a clinical response that was sustained during the 14 week treatment period. The 3 and 10 mg groups also achieved reduction of more than 75 percent in individual response variables, including swollen and painful joint counts.
Avakine in combination with methotrexate reduced tender and swollen joint counts to remission or near remission levels.
The drug works by binding to tumor necrosis factor alpha (TNF- alpha) on the cell membrane, neutralizing TNF-alpha in the blood and destroying cells that produce TNF- alpha.
Centocor plans to complete enrollment in an additional Phase III trial in RA by the end of the year.
Seattle-based Immunex first trumpeted Enbrel's Phase III trial success in September, but saved details of the trial, which met both primary and secondary endpoints, for the scientific meeting.
In the 234-patient Phase III trial, patients receiving a 25 mg dose of Enbrel twice a week experienced a median reduction of 71 percent in painful joint counts versus 6 percent in the placebo group. Patients in the Enbrel group also achieved a median 51 percent reduction in swollen joint counts, compared to 2 percent in the controls.
The twice-a-week 10 mg dosage level produced median reductions of 55 percent in painful joint counts, and a 49 percent reduction in swollen joint counts.
The study also measured patient improvement based on the American College of Rheumatology's (ACR) composite score, which combines measures of joint pain and swelling, and patient and physician assessments. A 20 percent improvement in ACR scores at three months was a primary endpoint.
At that point, 62 percent of the 25 mg-treated group had attained a 20 percent or greater improvement, along with 45 percent of the 10 mg group and 23 percent of the control patients.
Forty percent of patients in the 25 mg group sustained a 50 percent reduction in ACR scores at six months vs. 5 percent of the placebo patients.
The most frequently reported side effects were injection site reactions and minor colds. No patients dropped out of the study due to the colds and all were resolved by the end of the study.
Immunex's Stock Climbed On Enbrel Findings
"Data are exceptionally strong and support our view that Enbrel will become a major new treatment modality for rheumatoid arthritis," wrote analysts Kevin Tang and Dennis Harp of BT Alex. Brown Inc., in New York.
Enbrel is a tumor necrosis factor receptor that regulates inflammation by blocking the interaction of the proinflammatory cytokine TNF with the cells that respond to its signal. This Phase III trial achieved statistically significant positive results in patients with advanced rheumatoid arthritis, and another Phase III is under way in early stage patients to determine whether Enbrel can stall disease progression.
The drug's marketing partner is the Wyeth-Ayerst division of American Home Products Corp., of Madison, N.J., which owns 54 percent of Immunex. (See BioWorld Today, Sept. 29, 1997, p. 1.)
Immunex plans to submit a new drug application for Enbrel in 1998. Approval and initial marketing could come in 1999, with the first full year of sales likely in 2000, according to analyst Edmund Debler, of Mehta & Isaly, in New York.
Immunex's stock (NASDAQ:IMNX) closed Monday at $69.25, up $1.50. *