|
Article Excerpt
Business Editors/Health & Pharmaceutical Writers
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--April 11, 2002
Merck has re-released the news release announcing FDA approved changes to the label for Vioxx(R) (rofecoxib) with accompanying prescribing information and patient package insert.
A conference call was held by Merck earlier today for pharmaceutical industry analysts and news media to discuss this announcement.
If you were unable to listen to either call, the replay numbers are: Analyst conference call: (402) 998-0193 News media Q&A session: (973) 341-3080/ (PIN: 3225271) The replay numbers and the webcast will be active for one week on www.merck.com.
FDA Approves Label Changes for Vioxx(R)to Reflect Data
from Landmark Gastrointestinal Outcomes Study
and Approves New Indication for Adult Rheumatoid Arthritis
Merck & Co., Inc. announced today that the U.S. Food and Drug Administration has approved changes to the prescribing information for Vioxx(R) (rofecoxib) to include results from the landmark 8,000-patient Vioxx Gastrointestinal Outcomes Research (VIGOR) study. The FDA also has approved Vioxx 25 mg once daily for the relief of the signs and symptoms of rheumatoid arthritis in adults. Vioxx is the Company's once-daily medicine for osteoarthritis and acute pain in adults.
Vioxx is now the first and only medicine that selectively inhibits the COX-2 enzyme that is proven to reduce the risk of developing clinically important gastrointestinal (GI) side effects in patients with or without risk factors for such GI side effects compared to the non-steroidal anti-inflammatory drug (NSAID) naproxen. In VIGOR, Vioxx 50 mg -- a dose two-times the highest recommended chronic dose -- significantly reduced serious GI side effects, including perforations, obstructions, ulcers and bleeds, by 54 percent compared to a commonly used dose of naproxen (1,000 mg) in rheumatoid arthritis patients. The GI safety benefit compared to naproxen, as shown in VIGOR, now appears as a modification to the GI Warning section of the prescribing information, a section included in the prescribing information for all NSAIDs, including those that selectively inhibit COX-2.
The prescribing information also has been revised to include cardiovascular data from VIGOR. In this study, the number of patients with serious cardiovascular thrombotic events in the group treated with Vioxx 50 mg (n=45) was higher than in the group taking naproxen (n=19). In a placebo-controlled database derived from two other studies (n=2,142), the number of patients with serious cardiovascular thrombotic events among those receiving Vioxx 25 mg was 21 compared to 35 for patients taking placebo. These data also are reflected in the prescribing information. The significance of the cardiovascular findings from these three studies (VIGOR and the placebo-controlled studies) is unknown. Vioxx is not a substitute for aspirin to prevent cardiovascular events because of its lack of effect on platelets. The Precautions section of the prescribing information states that all of this information should be taken into consideration and caution should be exercised when Vioxx is used in patients with a medical history of ischemic heart disease, which includes patients with a history of angina or heart attack.
"Merck is confident in the efficacy and safety profile of Vioxx. VIGOR was a rigorous test of the GI safety of Vioxx versus naproxen and based on that study, the FDA has approved a modification to the standard GI warning section. Our label now reads: `Although the risk of GI toxicity is not completely eliminated with Vioxx, the results of the VIGOR study demonstrate that in patients treated with Vioxx, the risk of GI toxicity with Vioxx 50 mg once daily is significantly less than with naproxen 500 mg twice daily,'" said Edward M. Scolnick, M.D., executive vice president, science and technology, and president, Merck Research Laboratories, Merck & Co., Inc.
Vioxx reduced risk of GI damage in rigorous GI outcomes study
In the large GI outcomes study known as VIGOR, Vioxx 50 mg once daily (n=4,047) -- a dose twice the highest recommended chronic dose -- was compared to a common therapeutic dose of naproxen 500 mg twice daily (n=4,029) in patients with rheumatoid arthritis (median length of participation was nine months). The study assessed the incidence of serious GI events and the most serious, or "complicated," GI events, which included perforations, obstructions or major bleeding (PUB) in the upper GI tract. The study was designed to exclude patients requiring aspirin for cardioprotection.
In VIGOR, Vioxx 50 mg once daily significantly reduced the risk of serious GI events by 54 percent and the risk of complicated GI events by 57 percent compared to naproxen 500 mg twice daily. A total of 56 patients treated with Vioxx experienced a serious GI event compared to 121 patients taking naproxen, and a total of 16 patients receiving Vioxx had a complicated GI event versus 37 patients taking naproxen.
In the study, the reduction in risk for serious and complicated GI events with Vioxx was maintained in patients both at high risk for developing a PUB and in patients without risk factors. Such risk factors include: prior history of a PUB, age of 65 or older, Helicobacter pylori infection or concomitant use of corticosteroids.
Other safety findings in VIGOR: cardiovascular data
In VIGOR, a statistically significant higher incidence of serious cardiovascular thrombotic events was seen in patients receiving Vioxx 50 mg once daily compared to patients treated with naproxen 500 mg twice daily. A total of 45 serious cardiovascular thrombotic events occurred among 4,047 patients taking Vioxx compared to 19 among 4,029 taking naproxen. This was largely due to a difference in the incidence of non-fatal heart attacks: 18 for Vioxx and 4 for naproxen. The number of cardiovascular thrombotic deaths was similar in patients treated with Vioxx (n=7) compared to naproxen (n=6).
The GI and cardiovascular safety findings from VIGOR were published in The New England Journal of Medicine in November 2000 and publicly presented at an FDA Advisory Committee meeting in February 2001.
Also included in the prescribing information are data from a placebo-controlled database derived from two studies with a total of 2,142 elderly patients (mean age 75; Vioxx n=1,067, placebo n=1,075). The median exposure in these studies was approximately 14 months. The number of patients with a serious cardiovascular thrombotic event was 21 for patients treated with Vioxx 25 mg once daily versus 35 for patients receiving placebo. In these same two placebo-controlled studies, mortality due to cardiovascular thrombotic events was 8 versus 3 for Vioxx versus placebo, respectively. The significance of the cardiovascular findings from these three studies (VIGOR and the placebo-controlled studies) is unknown. Prospective studies with Vioxx to compare the incidence of serious cardiovascular events to NSAID comparators or placebo have not been performed.
GI side effects of NSAIDs
Serious GI side effects of NSAIDs are associated with an estimated 100,000 hospitalizations and an estimated 16,500 deaths each year in the United States.(1) Four out of 5 people who develop a serious GI side effect while taking a NSAID do not have warning symptoms.
New indication approved for treatment of adult rheumatoid arthritis
The efficacy and safety of Vioxx 25 mg once daily for the relief of the signs and symptoms of rheumatoid arthritis were evaluated in two 12-week studies involving nearly 2,000 patients that compared Vioxx 25 mg once daily to naproxen 500 mg twice daily. Results of these studies, which included extensions of up to one year, are included in the Clinical Studies and Adverse Events sections of the label.
In these studies, the adverse experience profile was generally similar to that reported in the osteoarthritis studies. In studies of at least three months, the incidence of hypertension in rheumatoid arthritis patients receiving Vioxx 25 mg once daily was 10.0 percent and the incidence of hypertension in patients receiving naproxen 500 mg twice daily was 4.7 percent.
Rheumatoid arthritis is a chronic, systemic inflammatory disease that affects more than 2 million Americans, mostly women.
"We are excited about the expanded use of Vioxx 25 mg as a once-daily treatment for adult rheumatoid arthritis," said Dr. Scolnick. "This new indication offers patients suffering from the pain and inflammation of this disease a new treatment option."
Important information about Vioxx
In rare cases, serious stomach problems, such as bleeding, can occur without warning symptoms. People who have had an allergic reaction, such as asthma, to Vioxx, aspirin or other arthritis medicines should not take Vioxx. People who have had liver or kidney problems, or are pregnant, should tell their doctors. Vioxx should not be used by women in late pregnancy.
Common side effects reported in the osteoarthritis clinical trials with Vioxx were upper-respiratory infection, diarrhea, nausea and high blood pressure.
About Vioxx
Vioxx was first approved in the United States in 1999 for the relief of the signs and symptoms of osteoarthritis, management of acute pain in adults and treatment of menstrual pain. Since its introduction, more than 52 million prescriptions have been written in the United States.(2)
The recommended starting dose of Vioxx for treatment of osteoarthritis is 12.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 25 mg once daily. For rheumatoid arthritis, the recommended dose is 25 mg once daily. The maximum daily dose for osteoarthritis and rheumatoid arthritis is 25 mg once daily. Vioxx 50 mg once daily is the recommended dose for acute pain and menstrual pain. The chronic use of Vioxx 50 mg is not recommended; use of Vioxx 50 mg for more than five days in the management of pain has not been studied.
Merck's 2002 sales guidance for its coxib franchise of $2.8 billion to $3.1 billion remains unchanged from guidance provided earlier this year.
Merck & Co., Inc. is a leading research-driven pharmaceutical products and services 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. Merck-Medco manages pharmacy benefits for employers, insurers and other plan sponsors, encouraging the appropriate use of medicines and providing disease management programs.
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. We undertake 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 document should be evaluated together with the many...
|
