Regeneron Reports Phase II Results for IL-1 Trap Clinical Program in Rheumatoid Arthritis
IL-1 Trap Phase II Study Demonstrates Clinical Activity and Favorable Safety and Tolerability Profile
TARRYTOWN, N.Y.--(BUSINESS WIRE)--Oct. 7, 2003-- Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN - News) announced today that the Company's IL-1 Trap demonstrated evidence of efficacy and safety in patients with rheumatoid arthritis (RA) in a Phase II dose-ranging study in approximately 200 patients. Patients treated with the highest dose, 100 milligrams (mg), of the IL-1 Trap exhibited improvements in primary and secondary end-points of the trial. When compared with placebo, subjects receiving 100 mg of IL-1 Trap demonstrated the following clinical and laboratory effects:
* An increase in the proportion of ACR 20 responses (primary endpoint) - 46% vs. 30.9% (p=0.11)
* An increase in the average ACR-N Score - 24.1% vs. 13.5%, (p=0.02)
* An increase in the proportion of ACR 50 responses - 20.0 % vs. 9.1%, (p=0.11)
* An increase in the proportion of ACR 70 responses - 12.0 % vs. 3.6%, (p=0.11)
* A greater decrease in the Disease Activity Score (DAS) - -1.1 vs. -0.7 (p=0.02)
* A faster time of onset of ACR 20 response (median time to onset) - 36 days vs. 77 days (p=0.03)
* Increased benefit in those patients on concomitant disease modifying anti-rheumatic drugs (DMARDs) - ACR 20 of 50.0% vs. 33.3%, (p=0.16) and ACR 50 of 29.4% vs. 11.1% (p=0.06)
* A decrease in C-Reactive Protein (CRP) a systemic marker of inflammation - -1.36 vs. + 0.07 (p=0.004)
The IL-1 Trap was generally well tolerated and was not associated with any serious adverse events. Of the patients treated with the IL-1 Trap, less than 5 percent developed antibodies against the molecule.
"This positive study, demonstrating evidence for clinical efficacy and the lack of safety concerns, clearly supports further development of this exciting new agent that is being studied for the treatment of patients with rheumatoid arthritis," said Larry Moreland, M.D., Professor of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham School of Medicine.
"This Phase II study provides strong evidence for clinical activity of the IL-1 Trap in rheumatoid arthritis. Moreover, it appears that we may not yet have achieved the optimal dose level, allowing for the potential of even greater efficacy at higher doses," said Leonard S. Schleifer, M.D., Ph.D., Regeneron's President and Chief Executive Officer. "We plan to move quickly to complete our detailed evaluation of these results and work with Novartis to determine the most efficient path forward for the IL-1 Trap in rheumatoid arthritis. Furthermore, given the favorable safety profile observed, we also intend to pursue a broader clinical development program for this promising molecule in several additional therapeutic categories."
Regeneron and Novartis Pharma AG, who formed a collaborative arrangement to develop and commercialize the IL-1 Trap, indicated that they will be working together to evaluate the data gathered in the study and determine the best path forward for the next clinical study.
Trial Design and Preliminary Data Summary
The multi-center Phase II trial was a randomized, placebo-controlled, double-blind study in people with active RA who have had an inadequate response to at least one disease-modifying anti-rheumatic drug (DMARDs). The study included approximately 200 participants, who were randomized equally into placebo or one of three fixed-dose groups (25, 50, or 100 mg) and received weekly subcutaneous injections. A substantial proportion of the subjects in each group were on DMARDs at baseline and continued their treatment with DMARDs during the trial (65%, 63%, 60%, and 68% of patients in the placebo, 25 mg, 50 mg, and 100 mg groups, respectively). The double-blind treatment period ran for 12 weeks, and participants were evaluated for 10 weeks following the cessation of treatment for safety and to track disease progression. The American College of Rheumatology (ACR20) criteria for improvement in RA as a function of IL-1Trap dose was the pre-specified primary efficacy endpoint. ACR50, ACR70, and ACR-N scores and other measures of disease activity were evaluated as secondary efficacy and exploratory endpoints.
The data from the study is summarized in the table below:
100 mg
vs. Pbo
Placebo 25 mg 50 mg 100 mg p value
Intent to Treat (ITT)
Last Observation Carried
Forward (LOCF) n = 55 n = 46 n = 48 n = 50
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ACR 20 (%) 30.9 34.8 20.8 46.0 0.11
ACR 50 (%) 9.1 17.4 10.4 20.0 0.11
ACR 70 (%) 3.6 2.2 2.1 12.0 0.11
Sustained ACR 20 (%) 12.7 19.6 18.8 30.0 0.03
Sustained ACR 50 (%) 3.6 0 4.2 10 0.19
ACR-N (%) 13.5 18.0 13.2 24.1 0.02
ACR-N AUC 787 1146 988 1357 0.02
CRP (mean change) mg/dL 0.072 -0.675 -1.021 -1.363 0.004
n = 53 n = 44 n = 48 n = 50
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Disease Activity Score -0.70 -0.88 -0.85 -1.12 0.02
n = 53 n = 43 n =47 n = 48
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Disease Activity Score AUC 394 367 391 345 0.008
Patients on DMARDs n = 36 n = 29 n = 29 n = 34
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ACR 20 (%) 33.3 34.5 27.6 50.0 0.16
ACR 50 (%) 11.1 17.2 13.8 29.4 0.06
ACR 70 (%) 5.6 0.0 3.4 17.6 0.11
Safety and Tolerability
The IL-1 Trap appeared to have a favorable safety and tolerability profile. There was no evidence of an increased rate of infection and no clinically significant effect on laboratory parameters, including hematology, serum chemistries, or vital signs. Only two serious adverse events, both of which occurred in the off-treatment period, were reported among treated patients and were not considered related to the IL-1 Trap. The most common side effect was a generally mild to moderate injection-site reaction. This reaction is, in part, associated with the formulation used for this trial, which will be changed for subsequent trials. Other side effects were experienced infrequently and do not appear to be dose-related. Antibodies were not dose-related and occurred in only a very small proportion (less than 5 percent) of treated patients and were not dose-related.
Webcast:
Leonard S. Schleifer, M.D., Ph.D., President & CEO of Regeneron Pharmaceuticals, Inc. invites you to join him and members of senior management from Regeneron in a webcast with the investment community to discuss the results of the Phase II trial for the IL-1 Trap on Tuesday, October 7, 2003 at 10:00 a.m. Eastern; 9:00 a.m. Central; 8:00 a.m. Mountain; and 7:00 a.m. Pacific.
The audio portion of the conference call will be available live, with accompanying slides, by webcast at www.regeneron.com on the Events page, under the Investor heading. The online archive as well as the dial-in replay of the call will be available for 30 days, beginning approximately two hours after the live call ends at the following numbers:
USA / Canada Replay Dial-In: (800) 642-1687
International Replay Dial-In: (706) 645-9291
Conference Call ID# 3084565 |
