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Tester32 · 19-10-2004, 14:35

Press Release Source: Merck & Co., Inc.

New Study Showed Investigational Medicine ARCOXIA Had Improved Gastrointestinal Tolerability Compared with Diclofenac Sodium

Tuesday October 19, 9:01 am ET

ARCOXIA and Diclofenac Had Similar Rates of Cardiovascular Thrombotic Events in One-Year Study with 7,000 Patients with Osteoarthritis

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Oct. 19, 2004-- In a new clinical study being presented today at the annual meeting of the American College of Rheumatology in San Antonio, ARCOXIA(TM) (etoricoxib) demonstrated significantly fewer discontinuations due to gastrointestinal (GI) side effects compared to diclofenac sodium, a commonly prescribed non-steroidal anti-inflammatory drug (NSAID). In this one-year study, known as the EDGE (Etoricoxib Diclofenac Gastrointestinal Evaluation) study, the rates of confirmed thrombotic cardiovascular events were similar for ARCOXIA and diclofenac sodium.

ARCOXIA is Merck & Co., Inc.'s investigational COX-2 specific inhibitor for arthritis and pain currently under review by the U.S. Food and Drug Administration. The goal Prescription Drug User Fee Act date for the New Drug Application for ARCOXIA is Oct. 30.

"The gastrointestinal and cardiovascular safety results from the EDGE study are consistent with data from the ongoing clinical development program for ARCOXIA, and add to the data already available on the safety profile of ARCOXIA," said Sean Curtis, M.D., senior director, clinical research, Merck & Co., Inc.

Design of EDGE study

The EDGE study was a randomized, double-blind, multi-center clinical trial that included osteoarthritis patients who were assigned to either ARCOXIA 90 mg once daily (n=3,593) - 1.5 times the maximum recommended dose for osteoarthritis - or diclofenac sodium 50 mg three times daily (n=3,518) for one year. Patients were treated for up to 16.5 months (mean duration of nine months), and were evaluated at screening, baseline, and months 1, 4, 8 and 12.

The study included patients 50 years or older (mean age 64) with a clinical diagnosis of osteoarthritis (knee, hip, hand or spine) requiring chronic treatment. Patients were allowed to take gastroprotective agents (GPAs) and low-dose aspirin, per current clinical guidelines.(1) In the study for both treatment groups, about four percent of patients had a history of an upper GI event, 37 percent were considered high-risk for cardiovascular disease, 45 percent were currently diagnosed with hypertension and 28 percent were taking low-dose aspirin at baseline.

The primary endpoint of the study was GI tolerability, defined as the cumulative incidence of patients who discontinued from the study due to either a clinical or laboratory GI adverse experience.

Pre-specified endpoints of interest in the study included: overall safety and tolerability; discontinuations due to edema-related adverse events, hypertension-related adverse events, hepatic adverse events, and renal dysfunction; incidence of hepatic adverse events and congestive heart failure; and efficacy as determined by patient global assessment of disease. Thrombotic cardiovascular safety, an additional prespecified endpoint, was assessed by comparing the two treatment groups for all investigator-reported thrombotic cardiovascular events that were confirmed by an independent cardiovascular adjudication panel. Gastrointestinal perforations, ulcers and bleeding (PUB) events were evaluated as an exploratory endpoint, although it was expected that these results would be confounded by GPA and low-dose aspirin use.

ARCOXIA reduced risk of discontinuations due to GI side effects by 50 percent

In the EDGE study, ARCOXIA significantly reduced the rate of discontinuations due to GI adverse events (clinical and laboratory) compared to diclofenac. There were 9.4 events per 100 patients per year for patients taking ARCOXIA versus 19.2 events for patients taking diclofenac sodium, for a risk reduction of 50 percent (p less than 0.001). Differences in GI discontinuation rates between the treatment groups remained significant when clinical and laboratory GI adverse events were evaluated separately, and the risk reduction favoring ARCOXIA was maintained in all subgroups evaluated, including the GPA and low-dose aspirin subgroups.

ARCOXIA and diclofenac had similar rates of serious cardiovascular thrombotic events

The EDGE study showed that there was no discernible difference in the number of confirmed thrombotic cardiovascular events between ARCOXIA and diclofenac. The relative risk of ARCOXIA compared to diclofenac was 1.07 (0.65, 1.74) for events that occurred within 14 days of discontinuing study treatment and 1.02 (0.64, 1.62) for events that occurred within 28 days of discontinuing study treatment. A relative risk of 1.00 means that the rate of events in patients in one treatment group is the same as the rate observed in the other treatment group.

This finding from the EDGE study is consistent with observations in the pooled analysis of controlled clinical studies for ARCOXIA that compared ARCOXIA (combined doses 60 mg, 90 mg or 120 mg) versus either placebo or the NSAIDs diclofenac 50 mg three times a day and ibuprofen 800 mg three times a day. The clinical studies in this pooled analysis, which included 6,700 patients, ranged up to 12 weeks for the placebo-controlled studies and up to 190 weeks for the NSAID-controlled studies. In the analysis, the relative risk for confirmed serious cardiovascular thrombotic events when ARCOXIA was compared to placebo was 1.11 (0.32, 3.81) and when ARCOXIA was compared to diclofenac and ibuprofen combined was 0.83 (0.26, 2.64). When ARCOXIA was compared to naproxen in the pooled analysis, the relative risk was 1.70 (0.91, 3.18) favoring naproxen.

In the EDGE study, each individual cardiovascular event type included in the prespecified composite cardiovascular endpoint was analyzed, and there was no significant difference in rates between ARCOXIA and diclofenac. The rates (per 100 patient years) of myocardial infarction occurring within 14 days after study therapy was discontinued were 0.68 for ARCOXIA and 0.42 for diclofenac. The rates (per 100 patient years) of stroke occurring within 14 days after study therapy was discontinued were 0.15 for ARCOXIA and 0.23 for diclofenac.

"The EDGE study showed there were similar rates of thrombotic cardiovascular events between ARCOXIA and diclofenac in a patient population that appropriately represents the actual clinical setting," said Dr. Curtis. "This observation was made in a broad group of patients who had a number of different medical conditions, including pre-existing cardiovascular disease."

ARCOXIA was generally well tolerated

In the EDGE study, fewer patients discontinued for any adverse event with ARCOXIA compared to diclofenac. Hepatic adverse events and discontinuations due to hepatic adverse events were more common with diclofenac than ARCOXIA.

Also in the study, significantly fewer patients taking diclofenac (0.7 percent) discontinued the study due to hypertension-related adverse events compared to patients taking ARCOXIA 90 mg (2.3 percent) (p less than 0.001). In looking at the clinical development program for ARCOXIA, the rate of discontinuations due to hypertension adverse events for ARCOXIA 90 mg - at a dose 1.5 times the proposed maximum recommended osteoarthritis dose - was generally similar to rates observed with comparator NSAIDs (naproxen 1,000 mg and ibuprofen 2,400 mg).

Efficacy data for ARCOXIA also presented

Data from efficacy studies evaluating ARCOXIA versus naproxen in the treatment of ankylosing spondylitis and ARCOXIA versus indomethacin in the treatment of acute gouty arthritis also are being presented at the annual meeting of the American College of Rheumatology.

About ARCOXIA and Merck

The Food and Drug Administration currently is reviewing Merck's New Drug Application for ARCOXIA, which seeks indications for the treatment of osteoarthritis, rheumatoid arthritis, chronic low back pain, acute pain, dysmenorrhea (menstrual pain), acute gouty arthritis and ankylosing spondylitis. ARCOXIA has been launched in 48 countries worldwide in Europe, Latin America and the Asia-Pacific region.

Merck & Co., Inc. is a global research-driven pharmaceutical products company. Merck discovers, develops, manufactures and markets a broad range of innovative products to improve human and animal health, directly and through its joint ventures.

Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2003, and in its periodic reports on Form 10-Q and Form 8-K (if any) which the company incorporates by reference.

(1) ACR Subcommittee on OA Guidelines. Recommendations for the medical
management of OA of the hip and knee: 2000 update. Arthritis Rheum
2000; 43: 1905-15.
American Heart Association (AHA). Aspirin in Heart Attack and Stroke
Prevention: AHA Recommendation.
http://www.americanheart.org/present...entifier=4456, Accessed
August 16, 2004.

ARCOXIA(TM) is a trademark of Merck & Co., Inc.

--------------------------------------------------------------------------------
Contact:
Media Contacts:
Anita Larsen, 917-833-7761
OR
Tracy Ogden, 484-686-4837
OR
Investor Contact:
Michael Rabinowitz, 908-423-5185

--------------------------------------------------------------------------------
Source: Merck & Co., Inc.

Kommentar: So wie es aussieht, wird Arcoxia von der FDA zugelassen. Bisher hat die FDA wohl auch keine Einwände gegen Vioxx erhoben, der Rückruf war von Merck freiwillig.

19-10-2004, 14:35	#35
Tester32 TBB Family Registriert seit: Jan 2004 Beiträge: 2.209	News zu Arcoxia Press Release Source: Merck & Co., Inc. New Study Showed Investigational Medicine ARCOXIA Had Improved Gastrointestinal Tolerability Compared with Diclofenac Sodium Tuesday October 19, 9:01 am ET ARCOXIA and Diclofenac Had Similar Rates of Cardiovascular Thrombotic Events in One-Year Study with 7,000 Patients with Osteoarthritis WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Oct. 19, 2004-- In a new clinical study being presented today at the annual meeting of the American College of Rheumatology in San Antonio, ARCOXIA(TM) (etoricoxib) demonstrated significantly fewer discontinuations due to gastrointestinal (GI) side effects compared to diclofenac sodium, a commonly prescribed non-steroidal anti-inflammatory drug (NSAID). In this one-year study, known as the EDGE (Etoricoxib Diclofenac Gastrointestinal Evaluation) study, the rates of confirmed thrombotic cardiovascular events were similar for ARCOXIA and diclofenac sodium. ARCOXIA is Merck & Co., Inc.'s investigational COX-2 specific inhibitor for arthritis and pain currently under review by the U.S. Food and Drug Administration. The goal Prescription Drug User Fee Act date for the New Drug Application for ARCOXIA is Oct. 30. "The gastrointestinal and cardiovascular safety results from the EDGE study are consistent with data from the ongoing clinical development program for ARCOXIA, and add to the data already available on the safety profile of ARCOXIA," said Sean Curtis, M.D., senior director, clinical research, Merck & Co., Inc. Design of EDGE study The EDGE study was a randomized, double-blind, multi-center clinical trial that included osteoarthritis patients who were assigned to either ARCOXIA 90 mg once daily (n=3,593) - 1.5 times the maximum recommended dose for osteoarthritis - or diclofenac sodium 50 mg three times daily (n=3,518) for one year. Patients were treated for up to 16.5 months (mean duration of nine months), and were evaluated at screening, baseline, and months 1, 4, 8 and 12. The study included patients 50 years or older (mean age 64) with a clinical diagnosis of osteoarthritis (knee, hip, hand or spine) requiring chronic treatment. Patients were allowed to take gastroprotective agents (GPAs) and low-dose aspirin, per current clinical guidelines.(1) In the study for both treatment groups, about four percent of patients had a history of an upper GI event, 37 percent were considered high-risk for cardiovascular disease, 45 percent were currently diagnosed with hypertension and 28 percent were taking low-dose aspirin at baseline. The primary endpoint of the study was GI tolerability, defined as the cumulative incidence of patients who discontinued from the study due to either a clinical or laboratory GI adverse experience. Pre-specified endpoints of interest in the study included: overall safety and tolerability; discontinuations due to edema-related adverse events, hypertension-related adverse events, hepatic adverse events, and renal dysfunction; incidence of hepatic adverse events and congestive heart failure; and efficacy as determined by patient global assessment of disease. Thrombotic cardiovascular safety, an additional prespecified endpoint, was assessed by comparing the two treatment groups for all investigator-reported thrombotic cardiovascular events that were confirmed by an independent cardiovascular adjudication panel. Gastrointestinal perforations, ulcers and bleeding (PUB) events were evaluated as an exploratory endpoint, although it was expected that these results would be confounded by GPA and low-dose aspirin use. ARCOXIA reduced risk of discontinuations due to GI side effects by 50 percent In the EDGE study, ARCOXIA significantly reduced the rate of discontinuations due to GI adverse events (clinical and laboratory) compared to diclofenac. There were 9.4 events per 100 patients per year for patients taking ARCOXIA versus 19.2 events for patients taking diclofenac sodium, for a risk reduction of 50 percent (p less than 0.001). Differences in GI discontinuation rates between the treatment groups remained significant when clinical and laboratory GI adverse events were evaluated separately, and the risk reduction favoring ARCOXIA was maintained in all subgroups evaluated, including the GPA and low-dose aspirin subgroups. ARCOXIA and diclofenac had similar rates of serious cardiovascular thrombotic events The EDGE study showed that there was no discernible difference in the number of confirmed thrombotic cardiovascular events between ARCOXIA and diclofenac. The relative risk of ARCOXIA compared to diclofenac was 1.07 (0.65, 1.74) for events that occurred within 14 days of discontinuing study treatment and 1.02 (0.64, 1.62) for events that occurred within 28 days of discontinuing study treatment. A relative risk of 1.00 means that the rate of events in patients in one treatment group is the same as the rate observed in the other treatment group. This finding from the EDGE study is consistent with observations in the pooled analysis of controlled clinical studies for ARCOXIA that compared ARCOXIA (combined doses 60 mg, 90 mg or 120 mg) versus either placebo or the NSAIDs diclofenac 50 mg three times a day and ibuprofen 800 mg three times a day. The clinical studies in this pooled analysis, which included 6,700 patients, ranged up to 12 weeks for the placebo-controlled studies and up to 190 weeks for the NSAID-controlled studies. In the analysis, the relative risk for confirmed serious cardiovascular thrombotic events when ARCOXIA was compared to placebo was 1.11 (0.32, 3.81) and when ARCOXIA was compared to diclofenac and ibuprofen combined was 0.83 (0.26, 2.64). When ARCOXIA was compared to naproxen in the pooled analysis, the relative risk was 1.70 (0.91, 3.18) favoring naproxen. In the EDGE study, each individual cardiovascular event type included in the prespecified composite cardiovascular endpoint was analyzed, and there was no significant difference in rates between ARCOXIA and diclofenac. The rates (per 100 patient years) of myocardial infarction occurring within 14 days after study therapy was discontinued were 0.68 for ARCOXIA and 0.42 for diclofenac. The rates (per 100 patient years) of stroke occurring within 14 days after study therapy was discontinued were 0.15 for ARCOXIA and 0.23 for diclofenac. "The EDGE study showed there were similar rates of thrombotic cardiovascular events between ARCOXIA and diclofenac in a patient population that appropriately represents the actual clinical setting," said Dr. Curtis. "This observation was made in a broad group of patients who had a number of different medical conditions, including pre-existing cardiovascular disease." ARCOXIA was generally well tolerated In the EDGE study, fewer patients discontinued for any adverse event with ARCOXIA compared to diclofenac. Hepatic adverse events and discontinuations due to hepatic adverse events were more common with diclofenac than ARCOXIA. Also in the study, significantly fewer patients taking diclofenac (0.7 percent) discontinued the study due to hypertension-related adverse events compared to patients taking ARCOXIA 90 mg (2.3 percent) (p less than 0.001). In looking at the clinical development program for ARCOXIA, the rate of discontinuations due to hypertension adverse events for ARCOXIA 90 mg - at a dose 1.5 times the proposed maximum recommended osteoarthritis dose - was generally similar to rates observed with comparator NSAIDs (naproxen 1,000 mg and ibuprofen 2,400 mg). Efficacy data for ARCOXIA also presented Data from efficacy studies evaluating ARCOXIA versus naproxen in the treatment of ankylosing spondylitis and ARCOXIA versus indomethacin in the treatment of acute gouty arthritis also are being presented at the annual meeting of the American College of Rheumatology. About ARCOXIA and Merck The Food and Drug Administration currently is reviewing Merck's New Drug Application for ARCOXIA, which seeks indications for the treatment of osteoarthritis, rheumatoid arthritis, chronic low back pain, acute pain, dysmenorrhea (menstrual pain), acute gouty arthritis and ankylosing spondylitis. ARCOXIA has been launched in 48 countries worldwide in Europe, Latin America and the Asia-Pacific region. Merck & Co., Inc. is a global research-driven pharmaceutical products company. Merck discovers, develops, manufactures and markets a broad range of innovative products to improve human and animal health, directly and through its joint ventures. Forward-Looking Statement This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2003, and in its periodic reports on Form 10-Q and Form 8-K (if any) which the company incorporates by reference. (1) ACR Subcommittee on OA Guidelines. Recommendations for the medical management of OA of the hip and knee: 2000 update. Arthritis Rheum 2000; 43: 1905-15. American Heart Association (AHA). Aspirin in Heart Attack and Stroke Prevention: AHA Recommendation. http://www.americanheart.org/present...entifier=4456, Accessed August 16, 2004. ARCOXIA(TM) is a trademark of Merck & Co., Inc. -------------------------------------------------------------------------------- Contact: Media Contacts: Anita Larsen, 917-833-7761 OR Tracy Ogden, 484-686-4837 OR Investor Contact: Michael Rabinowitz, 908-423-5185 -------------------------------------------------------------------------------- Source: Merck & Co., Inc. Kommentar: So wie es aussieht, wird Arcoxia von der FDA zugelassen. Bisher hat die FDA wohl auch keine Einwände gegen Vioxx erhoben, der Rückruf war von Merck freiwillig.