Table of Contents
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities and Exchange Act of 1934
Date of Report (Date of earliest event reported): September 4, 2008 (September 3, 2008)
REGENERON PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
| New York | 000-19034 | 13-3444607 | ||
| (State or other jurisdiction of | (Commission File Number) | (I.R.S. Employer | ||
| incorporation) | Identification Number) |
| 777 Old Saw Mill River Road, Tarrytown, New York | 10591-6707 | |
| (Address of principal executive offices) | (Zip Code) | |
(914) 347-7000
(Registrant’s telephone number, including area code)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the
filing obligation of registrant under any of the following provisions:
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17
CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17
CFR 240.13e-4(c))
TABLE OF CONTENTS
| Item 8.01 Other Events | ||||||||
| Item 9.01 Financial Statements and Exhibits | ||||||||
| Exhibit Index | ||||||||
| EX-99.A: PRESS RELEASE | ||||||||
| EX-99.B: SLIDES FOR WEBCAST | ||||||||
Table of Contents
| Item 8.01 | Other Events | |
| On September 3, 2008, Regeneron Pharmaceuticals, Inc. issued a press release announcing results of a Phase 2 study evaluating the efficacy and safety of ARCALYST® (rilonacept) versus placebo in the prevention of gout flares induced by the initiation of uric acid-lowering drug therapy that is used to control gout. A copy of this press release is attached as Exhibit 99(a) to this Form 8-K and is incorporated herein by reference. | ||
| On September 3, 2008, Regeneron’s President and Chief Executive Officer, Dr. Leonard Schleifer, and other members of senior management of Regeneron hosted a webcast conference call to discuss the findings of a Phase 2 study evaluating the efficacy and safety of ARCALYST® (rilonacept) versus placebo in the prevention of gout flares induced by the initiation of uric acid-lowering drug therapy that is used to control gout. The slides for this webcast are furnished as Exhibit 99(b) to this Form 8-K. |
| Item 9.01 | Financial Statements and Exhibits | |
| (c) Exhibits | ||
| 99(a) Press release dated September 3, 2008 announcing results of a Phase 2 study evaluating the efficacy and safety of ARCALYST® (rilonacept) versus placebo in the prevention of gout flares induced by the initiation of uric acid-lowering drug therapy that is used to control gout. | ||
| 99(b) Slides for September 3, 2008 webcast to discuss the findings of a Phase 2 study evaluating the efficacy and safety of ARCALYST® (rilonacept) versus placebo in the prevention of gout flares induced by the initiation of uric acid-lowering drug therapy that is used to control gout. |
Pursuant to the requirements of the Securities and Exchange Act of 1934, the registrant has
duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| REGENERON PHARMACEUTICALS, INC. |
||||
| Dated: September 4, 2008 | By: | /s/ Stuart Kolinski | ||
| Stuart Kolinski | ||||
| Senior Vice President and General Counsel | ||||
2
Table of Contents
Exhibit Index
| Number | Description | |
99(a)
|
Press release dated September 3, 2008 announcing results of a Phase 2 study evaluating the efficacy and safety of ARCALYST® (rilonacept) versus placebo in the prevention of gout flares induced by the initiation of uric acid-lowering drug therapy that is used to control gout. | |
99(b)
|
Slides for September 3, 2008 webcast to discuss the findings of a Phase 2 study evaluating the efficacy and safety of ARCALYST® (rilonacept) versus placebo in the prevention of gout flares induced by the initiation of uric acid-lowering drug therapy that is used to control gout. |
3
Exhibit 99.A
FOR IMMEDIATE RELEASE
Press Release
Regeneron’s ARCALYST® (rilonacept) Reduced Incidence of Gout Flares by 81 Percent in a
Phase 2 Study in Gout Patients Initiating Urate-lowering Therapy
Proportion of patients experiencing gout flares reduced from 45.2 percent to 14.6 percent
Tarrytown, NY (September 3, 2008) — Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) today announced
that treatment with ARCALYST® (rilonacept), also known as IL-1 Trap, in a Phase 2 study
of gout patients initiating therapy with allopurinol to lower their uric acid levels, produced a
statistically significant reduction versus placebo in the incidence of gout flares. In this
83-patient, double-blind, placebo-controlled study, the mean number of flares per patient over the
first 12 weeks of urate-lowering therapy was 0.79 with placebo and 0.15 with ARCALYST (p=0.0011),
an 81 percent reduction. This was the primary endpoint of the study. All secondary endpoints also
were met with statistical significance.
In the first 12 weeks of treatment, 45.2 percent of patients treated with placebo experienced a
gout flare and, of those, 47.4 percent had more than one flare. Among patients treated with
ARCALYST, only 14.6 percent experienced a gout flare (p=0.0037 versus placebo) and none had more
than one flare. No serious drug-related adverse events were reported in patients receiving
ARCALYST treatment. Injection-site reaction was the most commonly reported adverse event with
ARCALYST treatment. Detailed data from the study will be presented at a future scientific
conference.
This Phase 2 study evaluated the efficacy and safety of ARCALYST versus placebo in the prevention
of gout flares induced by the initiation of uric acid-lowering drug therapy that is used to control
gout. ARCALYST patients received an initial 320 milligram (mg) dose, followed by weekly doses of
160 mg. Gout is characterized by high blood levels of uric acid, a bodily waste product normally
excreted by the kidneys. The uric acid can form crystals in the joints of the toes, ankles, knees,
wrists, fingers, and elbows. Chronic treatment with uric acid-lowering medicines, such as
allopurinol, is prescribed to eliminate the uric acid crystals and prevent reformation. 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. These painful flares generally
persist for at least five days. In this study a gout flare was defined as patient-reported acute
joint pain that was deemed by the patient and/or investigator to require rescue treatment with an
anti-inflammatory drug.
“These findings could be significant in the future management of patients with gout in that they
address an impediment to successful long-term treatment. Allopurinol therapy is an important
approach to lowering patients’ high uric acid levels, which is the cause of their gout. However,
the increased risk of painful gout flares over the first few months of initiation of uric
acid-lowering therapy makes it difficult for patients to stick with treatment,” said John Sundy,
M.D.,
Ph.D., Division of Rheumatology, Department of Medicine, Duke University Medical Center.
“Currently, colchicine or anti-inflammatory drugs are recommended for use to reduce the risk of
gout flares in patients taking allopurinol, but these drugs may cause side effects and some
patients do not tolerate them. The results from this study suggest that concomitant use of
rilonacept during the first several months of allopurinol therapy may help avoid gout flares, which
could, in turn, improve patient outcomes.”
“We are encouraged about the potential role of ARCALYST® (rilonacept) therapy in the
treatment of gout. The results of this study, together with the findings of a previous small study
of ARCALYST in patients with chronic, active gout, suggest that ARCALYST may provide utility in a
number of different gout patient populations,” stated George D. Yancopoulos, M.D., Ph.D., President
of Regeneron Research Laboratories. “Based upon these results, we plan to initiate a Phase 3
clinical development program early next year with ARCALYST in the prevention of gout flares in
patients initiating urate-lowering drug therapy. Studies in other gout settings are also planned.”
Conference Call
Regeneron will host a webcast conference call to discuss these results today, September 3, 2008, at
8:30 a.m., Eastern Time. The dial-in information is:
Domestic Dial-in Number: (866)314-5050
International Dial-in Number: (617)213-8051
Participant Passcode: 16355081
International Dial-in Number: (617)213-8051
Participant Passcode: 16355081
For those unable to participate during the call, a replay will be available from 10:30 a.m. Eastern
Time on September 3, 2008 through October 3, 2008. The call can be accessed by dialing:
Domestic Dial-in Number: (888)286-8010
International Dial-in Number: (617)801-6888
Participant Passcode: 58761816
International Dial-in Number: (617)801-6888
Participant Passcode: 58761816
The replay will be available over the Internet and can be accessed by visiting the Regeneron
website at www.regeneron.com on the Presentations page of the Investor Relations section.
About Gout
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. More than three million
Americans currently suffer from gout. Treatment guidelines recommend that patients with elevated
uric acid levels who experience multiple gout attacks each year should receive chronic
urate-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 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 prophylactic dosing
with colchicine, which include diarrhea, abdominal cramps, nausea, and vomiting, can limit
patients’ adherence to both colchicine and allopurinol treatment.
Rationale for the Clinical Exploration of Use of ARCALYST® (rilonacept) in the Treatment
of Gout
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.
ARCALYST 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 ARCALYST, IL-1 cannot bind to the
cell-surface receptors and is eventually eliminated from the body.
Important Information About ARCALYST
ARCALYST is indicated 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. IL-1 blockade may interfere with immune response to infections.
Serious, life-threatening infections have been reported in patients taking ARCALYST®
(rilonacept). ARCALYST should be discontinued if a patient develops a serious infection. Taking
ARCALYST with tumor necrosis factor inhibitors is not recommended because this may increase the
risk of serious infections. Treatment with ARCALYST should not be initiated in patients with
active or chronic infections. Patients should not receive a live vaccine while taking ARCALYST.
It is recommended that patients receive all recommended vaccinations prior to initiation of
treatment with ARCALYST. Patients should be monitored for changes in their lipid profiles and
provided with medical treatment if warranted. Hypersensitivity reactions associated with ARCALYST
administration have been rare. Please see the full Prescribing Information for ARCALYST, available
online at www.regeneron.com/ARCALYST-fpi.pdf.
About Regeneron Pharmaceuticals, Inc.
Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and
commercializes medicines for the treatment of serious medical conditions. In addition to
ARCALYST® (rilonacept) Injection for Subcutaneous Use, its first commercialized product,
Regeneron has therapeutic candidates in clinical trials for the potential treatment of cancer, eye
diseases, and inflammatory diseases and has preclinical programs in other diseases and disorders.
Additional information about Regeneron and recent news releases are available on Regeneron’s web
site at www.regeneron.com.
Forward Looking Statement
This news release discusses historical information and includes forward-looking statements about
Regeneron and its products, development programs, finances, and business, all of which involve a
number of risks and uncertainties, such as risks associated with preclinical and clinical
development of Regeneron’s drug candidates, determinations by regulatory and
administrative governmental authorities which may delay or restrict Regeneron’s ability to continue
to develop or commercialize its product and drug candidates, competing drugs that are superior to
Regeneron’s product and drug candidates, uncertainty of market acceptance of Regeneron’s product
and drug candidates, unanticipated expenses, the availability and cost of capital, the costs of
developing, producing, and selling products, the potential for any collaboration agreement,
including Regeneron’s agreements with the sanofi-aventis Group and Bayer HealthCare, to be canceled
or to terminate without any product success, risks associated with third party intellectual
property, and other material risks. A more complete description of these and other material risks
can be found in Regeneron’s filings with the United States Securities and Exchange Commission
(SEC), including its Form 10-K for the year ended December 31, 2007 and Form 10-Q for the quarter
ended June 30, 2008. Regeneron does not undertake any obligation to update publicly any
forward-looking statement, whether as a result of new information, future events, or otherwise
unless required by law.
###
Contact Information:
Investor Relations
914-345-7640
invest@regeneron.com
914-345-7640
invest@regeneron.com
Laura Lindsay
Corporate Communications
914-345-7800
laura.lindsay@regeneron.com
Corporate Communications
914-345-7800
laura.lindsay@regeneron.com
Lauren Tortorete
Media Relations
212-845-5609
ltortorete@biosector2.com
Media Relations
212-845-5609
ltortorete@biosector2.com
Exhibit 99.B
| Top-line Results of a Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, and Efficacy of Rilonacept (IL-1 Trap) for the Prevention of Gout Flares During Initiation of Allopurinol Therapy Regeneron Pharmaceuticals, Inc. Investors' Webcast September 3, 2008 |
| Except for historical information, the matters contained in this presentation may constitute forward-looking statements that involve risks and uncertainties, such as risks associated with preclinical and clinical development of Regeneron's drug candidates, determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize its product and drug candidates, competing drugs that are superior to Regeneron's product and drug candidates, uncertainty of market acceptance of Regeneron's product and drug candidates, unanticipated expenses, the availability and cost of capital, the costs of developing, producing, and selling products, the potential for any collaboration agreement, including Regeneron's agreements with the sanofi-aventis Group and Bayer HeathCare, to be canceled or to terminate without any product success, risks associated with third party intellectual property, and additional risks detailed from time to time in Regeneron's filings with the Securities and Exchange Commission (SEC). Please refer to Regeneron's recent Forms 10-K, 10-Q, and 8-K for additional information on the uncertainties and risk factors related to our business. Because forward-looking statements involve risks and uncertainties, actual results may differ materially from current results expected by Regeneron. Regeneron is providing this information as of the original date of this presentation and expressly disclaims any duty to update any information contained in these materials. Safe Harbor Statement |
| Gout Gout: a disease resulting from the deposition of monosodium urate crystals in the joints caused by excess serum uric acid (a bodily waste product normally excreted by the kidneys) Clinical manifestations: acute and chronic pain/inflammation of joints and surrounding tissue tophi development (deposits of crystallized uric acid) in the joints of the toes, ankles, knees, wrists, fingers, and elbows Prevalence: > 3 million in U.S. Treatment: resolve acute attacks with anti-inflammatory therapy reduce and maintain normal uric acid levels (< 6.0 mg/dL) |
| Allopurinol in the Treatment of Gout Role: reduces the production of uric acid to help normalize serum uric acid levels with chronic use Usage: over 1.3 million gout patients receive allopurinol treatment each year over 750,000 new gout patient starts are initiated with allopurinol each year Major treatment impediment: during first months of allopurinol therapy while uric acid blood levels are being reduced, uric acid crystal dissolution can result in stimulation of inflammatory mediators, causing acute flares of joint pain and inflammation adherence to allopurinol therapy is therefore low, potentially leading to continued gout symptoms and tophi progression Other drawbacks of allopurinol: rash related to hypersensitivity, leukopenia, GI disturbances |
| Gout: Evidence for Role of IL-1 Gout has IL-1-associated clinical features inflammation, fever, elevated acute phase response IL-1 is a major product of human white blood cells stimulated by monosodium urate crystals (Duff, 1983, Malawista 1985, Martinon, 2006) The NLRP-3 (cryopyrin) inflammasome is required for crystal-induced IL-1 production (Martinon, 2006) In gout, IL-1 appears to be higher in the inflammatory cascade than other inflammatory mediators (e.g., TNF and IL-6) IL-1 signaling is required for crystal-induced inflammation in in vivo knock-out models (Chen 2006) |
| Monosodium urate crystals internalized by monocytes activate the NLRP3 inflammasome which leads to the processing and release of IL-1^ IL-1^ induces the expression of adhesion molecules and chemokines which are critical for the recruitment of PMNs into the site of acute inflammation Martinon, 2006 Gout: Evidence for Role of IL-1(Continued) |
| Rilonacept (ARCALYST(r))): Structure and Characteristics Rilonacept: a dimeric fusion protein Specific blocker of IL-1, incorporating extracellular domains of the 2 receptor components required for IL-1 signalling IL-1RI (IL-1 receptor sub-type 1) IL-1RAcP (IL-1 receptor accessory protein) Molecular weight ~251 kDa Expressed in recombinant Chinese hamster ovary (CHO) cells 8.6 days circulation half-life in vivo, allowing for once-weekly dosing IL-1RAcP IL-R1 Fc region "Trapped" IL-1 2. |
| Mechanism of Action of Rilonacept Certain inflammatory responses arise from excessive release of activated IL-1^ Rilonacept blocks IL-1 signaling by acting as a soluble decoy receptor that binds IL-1 and prevents its interaction with cell surface receptors IL-1 and inflammation Mechanism of action of rilonacept |
| Cryopyrin-Associated Periodic Syndromes (CAPS): Rare, Inherited, Auto-inflammatory Diseases with Life-long, Debilitating Consequences CAPS are characterized by lifelong, recurrent symptoms of rash, chills/fever, joint pain, fatigue, and eye redness/pain Intermittent, debilitating disease flares/ exacerbations can be triggered at random by a slight cooling in temperature, stress, exercise, and other unidentified causes Underlying disease and its flares place a heavy burden on patients by preventing them from fully participating in daily professional, family, and social activities To avoid triggers that cause flares, patients adopt a compromised lifestyle with limitations on everyday activities that can be just as debilitating as the disease |
| Cryopyrin PYD CARD CARD CARD CARD Inflammasome NBS LRR Monocyte/Macrophage CAPS: Generally Caused by a Mutation in a Gene that Helps Regulate the Body's Innate Immune Response, Resulting in Overproduction of Interleukin-1^ (IL-1^) PYD Autosomal-dominant mutation of NLRP-3/CIAS1 gene (in many patients)2 IL-1^ overproduction ASC Activated caspase 1 Cleaves Nucleus Cardinal Secretory lysosome NF-?B CAPS symptoms IL-1 receptor Pro-IL-1^ Pro-IL-1^ IL-1^ IL-1^ Cryopyrin PYD CARD CARD CARD CARD Inflammasome NBS LRR Monocyte/Macrophage PYD Autosomal-dominant mutation of NLRP-3/CIAS1 gene (in many patients) IL-1^ overproduction |
| Phase 3 Program Showed Marked Reduction in CAPS Symptoms with Rilonacept, but Not with Placebo - -3 0 3 6 (n=23) (n=24) 5 4 3 2 1 0 Rilonacept Placebo 3rd Qtr 4th Qtr Pre-treatment Baseline 3.1 2.4 90 20.4 Endpoint 0.5 2.1 34.6 31.6 North 45.9 46.9 45 43.9 Pre-treatment Baseline Period Part A Treatment Period Rilonacept vs Placebo P<0.0001 Study Week Rilonacept (n=23) Placebo (n=24) Group Mean Daily KSS (95% CI:-2.4, -1.3) P<0.0001 - -2.6 ( 84%^) P<0.0001 - -0.3 ( 13%^) P=NS Group Mean KSS Over 21-day Period Group Mean Key Symptom Score (KSS) by Treatment Group Pre-treatment Baseline Endpoint |
| Important Information about Rilonacept Rilonacept is not indicated for use in gout. It is currently being studied in a Phase 2 exploratory trial in gout Rilonacept is indicated 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 age 12 and over 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. Please see the full Prescribing Information for rilonacept, available online at www.regeneron.com/ARCALYST-fpi.pdf |
| Gout Pilot Study of Rilonacept: Single-Blind, Placebo Run-In Study in Patients with Chronic Active Gout S D0 W2 W4 W6 W8 W14 xx xx xx x x x x x Two week placebo run-in Loading dose of rilonacept at Week 2 [2X 160 mg subcutaneously (SC)] followed by five weekly 160 mg SC injections of rilonacept Evaluations every 2 weeks, then follow-up 6 weeks after the last dose (Subject's Pain and Global Scores, Physician's Global Score , Joint assessment, and C-reactive protein) dose S = screening: D = day; W = week |
| Gout Pilot Study Findings: Patients' Pain Score Improved with Rilonacept but not with Placebo (0 = normal/none to 10 = severe) (LOCF; N = 10) -1 0 2 4 6 8 14 Placebo Rilonacept Screening Off Treatment ns* P<0.02** * - Wk 2 v D0 ** - Wk 8 v Wk 2 |
| Phase 2 Study Objectives Primary Objective To assess the activity of rilonacept in reducing the frequency of acute gout flares in hyperuricemic patients initiating allopurinol therapy compared to placebo Secondary Objective To assess the severity and duration of gout flares during initiation of allopurinol therapy To assess the safety and tolerability of rilonacept in patients receiving concomitant allopurinol |
| Phase 2 Study Design Multi-center, randomized double-blind, placebo- controlled trial in 83 hyperuricemic (serum uric acid > 7.5 mg/dL) patients with inter-critical gout Group 1- rilonacept 320mg on day 1, followed by rilonacept 160mg once a week for 16 weeks Group 2- placebo Patients in both treatment arms started on a daily dose of 300 mg allopurinol on Day 1 Dose was titrated upward in 100 mg increments (maximum 800 mg) monthly in patients not achieving a target serum uric acid level < 6.0 mg/dL Starting dose was adjusted downward in patients with renal impairment based upon creatinine clearance |
| Study Scheme Rilonacept 160 mg subcutaneously weekly Rilonacept 160 mg subcutaneously weekly Rilonacept 160 mg subcutaneously weekly Rilonacept 160 mg subcutaneously weekly Rilonacept 160 mg subcutaneously weekly Rilonacept 160 mg subcutaneously weekly Rilonacept 160 mg subcutaneously weekly Rilonacept 160 mg subcutaneously weekly Screening Follow-up Placebo subcutaneously weekly Placebo subcutaneously weekly Placebo subcutaneously weekly Placebo subcutaneously weekly Placebo subcutaneously weekly Placebo subcutaneously weekly Placebo subcutaneously weekly Placebo subcutaneously weekly Day -14 to Day -3 Day 1 to Week 16 Day 1 to Week 16 Day 1 to Week 16 Day 1 to Week 16 Day 1 to Week 16 Day 1 to Week 16 Day 1 to Week 16 Day 1 to Week 16 Day 42 after last dose of study drug Primary Endpoint: Week 12 |
| Patient Population Patients 18 years of age or older : Meeting the criteria of the American Rheumatism Association (ARA) for the classification of the acute arthritis of primary gout Serum uric acid ^ 7.5 mg/dL A self-reported history of ^ 2 gout flares in the year prior to the Screening Visit |
| Key Exclusion Criteria Acute gout flare within 2 weeks before Screening Visit Allergy to allopurinol Use of glucocorticoids or colchicine within 4 weeks before Screening Visit Use of NSAIDs within 2 weeks prior to the Screening Visit Use of allopurinol, probenecid, or sulfinipyrazone within 3 months prior to the Screening Visit |
| Efficacy Endpoints Primary Endpoint: The mean number of gout flares assessed from Day 1 to Week 12 * A gout flare was defined as patient-reported acute joint pain deemed by the patient and/or investigator to require rescue anti-inflammatory therapy (NSAIDs or glucocorticoids) Secondary Endpoints: The proportion of patients with one or more gout flares assessed from Day 1 to Week 12 The mean number of gout flare days assessed from Day 1 to Week 12 The mean number of days with the patient's pain score of 5 or more (from patient's daily diary) from Day 1 to Week 12 |
| Patient Disposition Placebo Rilonacept 160mg/kg Patients randomized & dosed 42 41 Patients who completed Week 12 33 40 Withdrawals before Week 12 9 1 Reasons for withdrawal before Week 12 [n(%)] - Lost to follow up - Lack of efficacy - Adverse event - Consent withdrawn - Other 4 (9.5%) 2 (4.8%) 2 (4.8%) 1 (2.4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (2.4%) Patients reached: - Week 4 - Week 8 - Week 12 37 (88.7%) 34 (81.0%) 33 (78.6%) 41 (100%) 40 (97.6%) 40 (97.6%) |
| Baseline Characteristics Placebo Rilonacept 160mg/kg Patients randomized 42 41 Male (%) 95.0 98.0 Age yrs mean (median) 50 (52) 52 (50) Prior mean number of gout flares/yr 4.4 4.7 Prior mean duration of gout flare (days) 5.4 6.0 Tophi present 6 2 |
| EFFICACY FINDINGS |
| Primary Endpoint: Mean Number of Gout Flares Per Patient Through Week 12 Placebo (n=42) Rilonacept (n=41) 0.79 0.15 Mean number of gout flares per patient 0.15 p < 0.0011 (33 flares) (6 flares) 0.79 81% ^ |
| Time to First Gout Flare Placebo Rilonacept Placebo Rilonacept censored Treatment Proportion of Subjects Gout-Flare Free 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 10 20 40 30 50 60 70 90 80 p=0.0003 Time to First Gout Flare (days) |
| Proportion of Patients with a Gout Flare Through Week 12 Placebo (n=42) Rilonacept (n=41) 45 15 Proportion of patients with a grout flare p < 0.004 45.2% 14.6% (19 patients) (6 patients) |
| Proportion of Patients with a Gout Flare Through Week 12 Placebo (n=42) Rilonacept (n=41) 45 15 Proportion of patients with a grout flare p < 0.004 45.2% 14.6% (19 patients) (6 patients) 47.4% > 1 flare 0 % > 1 flare |
| Mean Number of Days with a Pain Score > 5 (0-10 scale) Through Week 12 Placebo (n=42) Rilonacept (n=41) 2.02 0.22 Mean number of days with pain score > 5 0.22 days p < 0.001 2.02 days |
| SAFETY FINDINGS |
| Safety Summary No serious drug-related adverse events were reported with rilonacept Injection-site reaction was the most commonly reported adverse event reported with rilonacept treatment |
| Adverse Events Through Week 12 Placebo (n=42) Rilonacept (n=41) Any Adverse Event [n(%)] 23 (55%) 17 (42%) Number of patients who discontinued due to an AE [n (%)] 3 (7.1%) 1 (2.4%) Serious AEs [n (%)] 2 (4.8%) 1 (2.4%) |
| Number of Patients with ^ 1 Treatment-Emergent Adverse Event Through Week 12 (reported in at least 5% of patients in either group treated) High-level Term AE Category Placebo (n=42) Rilonacept (n=41) Injection/infusion site reaction 1 (2.4%) 4 (9.8%) Upper respiratory tract infections 4 (9.5%) 1 (2.4%) Joint-related signs/symptoms 4 (9.5%) 1 (2.4%) Liver function enzyme elevations 0 (0%) 3 (7.3%) Purine metabolism disorders NEC 3 (7.1%) 1 (2.4%) |
| 10% of rilonacept-treated patients and 19% of placebo- treated patients reported 1 infection or more 1 rilonacept-treated patient reported pyleonephritis 2 placebo-treated patients reported bronchitis 1 rilonacept-treated patient and 4 placebo-treated patients reported upper respiratory tract infections No serious infections were reported No tuberculosis or other opportunistic infections were reported Infections |
| Conclusions In a Phase 2 study of gout patients initiating therapy with allopurinol to lower their uric acid levels Rilonacept produced an 81% statistically significant reduction in the mean incidence of gout flares per patient versus placebo over the first 12 weeks of therapy 45.2% of patients treated with placebo experienced a gout flare (of those, 47.4% had > 1 flare) versus 14.6% of those treated with rilonacept (none had > 1 flare) No serious drug-related adverse events were reported in patients receiving rilonacept treatment Injection-site reaction was the most commonly reported adverse event with rilonacept treatment Based upon these results, the Phase 3 program in drug-induced gout flare prophylaxis is scheduled to begin in early 2009 and additional uses of rilonacept in the treatment of gout are being explored |