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Arcalyst (rilonacept) Meets Primary and All Secondary Endpoints in Phase 3 Trial of Prevention of Gout Flares in Patients Initiating Allopurinol Therapy

- Regeneron plans to file by mid-2011 for regulatory approval for ARCALYST in this setting assuming positive results from two ongoing studies

TARRYTOWN, N.Y., June 09, 2010 /PRNewswire-FirstCall/ -- Regeneron Pharmaceuticals, Inc. today announced that a Phase 3 study in gout patients initiating allopurinol therapy to lower their uric acid levels showed that ARCALYST (rilonacept), also known as IL-1 Trap, prevented gout attacks, as measured by the primary endpoint of the number of gout flares per patient over the 16 week treatment period.



ARCALYST was generally well tolerated with no reported drug-related serious adverse events. Injection site reaction, generally considered mild, was the most commonly reported adverse event with ARCALYST.


"Gout is a very painful and common form of arthritis that results from high levels of uric acid. Uric acid-lowering therapy, most commonly with allopurinol, is a mainstay of treatment to reduce gout flares over the long term. Paradoxically, the initiation of uric acid-lowering therapy often triggers an increase in frequency of gout attacks in the first several months of treatment that may lead to discontinuation of therapy," stated George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories. "This positive pivotal study showed that ARCALYST(R) (rilonacept) markedly reduced the occurrence of painful gout attacks in patients initiating uric acid-lowering therapy. We look forward to data from our second efficacy study in this setting and our larger safety study. If these additional studies are successful, we plan to file for regulatory approval by mid-2011."


"Chronic urate-lowering therapy is critical to control the symptoms and the resulting consequences of gout in the joints. We in the rheumatology community have long recognized the challenge of adherence to uric acid-lowering therapies. Data suggest that many patients discontinue allopurinol within the first few months of therapy, in part due to increased flares," said H. Ralph Schumacher, M.D., Professor of Medicine, University of Pennsylvania, Philadelphia, PA. "Current therapies recommended to reduce the risk of gout flares in patients taking uric acid-lowering therapy are under-prescribed, especially outside of rheumatology practice. While additional Phase 3 data are needed, the results from this study suggest that concomitant use of rilonacept during the first several months of uric acid-lowering therapy may help avoid gout flares, which could, in turn, improve patient outcomes."


Results of a Phase 3 study in patients presenting with an ongoing acute gout flare showed that compared to indomethacin, a non-steroidal anti-inflammatory drug considered a standard of care, there was no significant benefit from combining indomethacin with ARCALYST, as measured by the primary endpoint of the average intensity of gout pain from 24 to 72 hours after initiation of treatment. Patients treated with indomethacin alone experienced an average reduction in patient-reported pain scores (0 to 4 Likert scale where 0 represents no pain and 4 represents extreme pain) of 1.40 points from baseline compared to an average reduction of 1.55 points from baseline in patients treated with both indomethacin and ARCALYST (p=0.33). Patients who received ARCALYST alone experienced an average pain reduction of 0.69 points. Treatment with ARCALYST was generally well tolerated with no reported drug-related serious adverse events. The most commonly reported adverse event with ARCALYST was headache.



The North American-based (ventative tudy against ate-lowering drug-induced out xacerbations) study was a double-blind, placebo-controlled study which evaluated the number of gout flares per patient over the first 16 weeks following initiation of allopurinol therapy. In the trial, a gout flare was defined as patient-reported acute articular pain typical of a gout attack that is deemed (by patient and/or investigator) to require treatment with an anti-inflammatory therapeutic; presence of at least three of the following four signs/symptoms: joint swelling, redness, tenderness and pain, and at least one of the following: rapid onset of pain, decreased range of motion, joint warmth or other symptoms similar to a prior gout flare. A total of 241 patients were randomized on a 1:1:1 basis to receive one of the following treatment regimens:



Adverse event that occurred at a frequency of at least 5% in any study group were: injection site reaction (19.8% with ARCALYST(R) (rilonacept) 160 mg, 8.8% with ARCALYST 80 mg, and 1.3% with placebo), upper respiratory tract infection (9.9% with ARCALYST 160 mg, 8.8% with ARCALYST 80 mg, and 7.6% with placebo), lower respiratory tract infection (0% with ARCALYST 160 mg, 5.0% with ARCALYST 80 mg, and 2.5% with placebo), musculoskeletal pain/ discomfort (6.2% with ARCALYST 160 mg, 7.5% with ARCALYST 80 mg, and 8.9% with placebo), and headache, (3.7% with ARCALYST 160 mg, 6.3% with ARCALYST 80 mg, and 1.3% with placebo).


Detailed data from this study will be presented at future scientific conferences.



The North-American-based (tudy tilizing ilonacept in out xacerbations) study was a double blind, placebo-controlled, Phase 3 study that evaluated pain during the initial 72 hours of treatment in patients experiencing an acute gout attack. A total of 225 patients were randomized on a 1:1:1 basis to receive one of the following treatment regimens:



Adverse events reported at an incidence of at least 5% in any group were headache (7.8% indomethacin alone, 5.5% with indomethacin plus ARCALYST, and 10.8% with ARCALYST alone) and neurological signs and symptoms (dizziness; 5.2% with indomethacin alone, 4.1% with indomethacin plus ARCALYST, and 2.7% with ARCALYST alone).


Detailed data from this study will be presented at future scientific conferences.




The ongoing studies in the Phase 3 program with ARCALYST in gout include:





Regeneron will host a webcast conference call to discuss these results today, . The dial-in information is:


Domestic Dial-in Number: (877) 390-5538

International Dial-in Number: (408) 940-3843

Participant Passcode: 80129194


The live conference call is being webcast and it, and slides for the conference call, can be accessed on the "Newsroom" page of the Company's website, The webcast will be available for 30 days following the call.



Gout is a condition that occurs when the bodily waste product, uric acid, is deposited in the joints and/or soft tissues. In the joints, these uric acid crystals cause inflammation, which leads to pain, swelling, redness, heat, and stiffness in the joints. Treatment guidelines recommend that patients with elevated uric acid levels who experience multiple gout attacks each year should receive chronic uric acid-lowering therapy, such as allopurinol. Allopurinol reduces the production of uric acid in the body to prevent the occurrence of gout attacks with long-term use. Approximately 750,000 gout patients initiate allopurinol therapy each year. During the first months of allopurinol therapy while uric acid blood levels are being reduced, the break up of the uric acid crystals can result in stimulation of inflammatory mediators, including interleukin-1 (IL-1), resulting in acute flares of joint pain and inflammation. Anti-inflammatory therapy with colchicine is sometimes used to help prevent these flares. However, the side effects associated with colchicine, which include diarrhea, abdominal cramps, nausea, and vomiting, can limit patients' adherence to both colchicine and allopurinol treatment.



Interleukin-1 (IL-1) is a protein secreted by infection-fighting cells in the blood and tissues. In many cases, IL-1 acts as a messenger to help regulate immune and inflammatory responses by attaching to cell-surface receptors in cells that participate in the body's immune system. In excess, it can be harmful and has been shown to be a key driver of inflammation in a variety of diseases, including gout. In gout, uric acid crystals stimulate the production of IL-1, which causes an inflammatory response in the joints and surrounding tissues.


Rilonacept is an agent that inhibits IL-1. It is designed to attach to and neutralize IL-1 in the blood stream before the IL-1 can attach to cell-surface receptors and generate signals that can trigger disease activity in body tissue. Once attached to rilonacept, IL-1 cannot bind to the cell-surface receptors and is eventually eliminated from the body.



Rilonacept, marketed as ARCALYST, is currently indicated in the U.S. for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. Rilonacept is also approved, but not marketed, in the E.U. for the same patient population. The safety and efficacy of ARCALYST in the gout setting have not been evaluated by the Food and Drug Administration. ARCALYST is not approved for use in gout.


IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking rilonacept. Rilonacept should be discontinued if a patient develops a serious infection. Taking rilonacept with tumor necrosis factor inhibitors is not recommended because this may increase the risk of serious infections. Treatment with rilonacept should not be initiated in patients with active or chronic infections. Patients should not receive a live vaccine while taking rilonacept. It is recommended that patients receive all recommended vaccinations prior to initiation of treatment with rilonacept. Patients should be monitored for changes in their lipid profiles and provided with medical treatment if warranted. Hypersensitivity reactions associated with rilonacept administration have been rare.



Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions. In addition to ARCALYST(R) (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has therapeutic candidates in Phase 3 clinical trials for the potential treatment of gout, diseases of the eye (wet age-related macular degeneration and central retinal vein occlusion), and certain cancers. Additional therapeutic candidates are in earlier stage development programs in rheumatoid arthritis and other inflammatory conditions, pain, cholesterol reduction, allergic and immune conditions, and cancer. Additional information about Regeneron and recent news releases are available on Regeneron's web site at






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    Michael Aberman, M.D.                     Peter Dworkin
    Investor Relations                        Corporate Communications
    914.345.7799                              914.345.7800   




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Posted: June 2010