New results from two Phase III clinical trials shared at American College of Gastroenterology 2009 Annual Scientific Meeting in San Diego
October 27, 2009 – San Diego, CA – AstraZeneca (NYSE: AZN) and POZEN Inc.
(NASDAQ: POZN) today announced results from an analysis of two pivotal Phase III studies of VIMOVO™ (naproxen/esomeprazole magnesium), formerly known as PN 400, and enteric-coated (EC) naproxen alone in patients at risk for NSAID-associated ulcers.
Patients in the VIMOVO groups reported significantly better upper gastrointestinal (UGI) tolerability assessments compared to EC naproxen in both studies.1 These data from the PN400-301/302 studies were presented during an oral presentation at The American College of Gastroenterology (ACG) 2009 Annual Scientific Meeting in San Diego, CA.
The UGI tolerability endpoints in these studies included were the Severity of Dyspepsia Assessment (SODA) and the Overall Treatment Evaluation for Dyspepsia (OTE-DP). In these analyses, patients treated with VIMOVO showed a significantly greater reduction in SODA pain intensity scores from baseline vs. EC naproxen: -5.51 vs. -0.15 (p<0.001) for study 301 and
-2.64 vs. 0.09 (P=0.004) for study 302. Additionally, patients treated with VIMOVO showed greater reduction in SODA non-pain symptoms scores from baseline vs. EC naproxen: -2.16 vs. -0.47 (p<0.001) for study 301 and
-1.11 vs. 0.11 (p<0.001) for study 302; and in SODA satisfaction scores from baseline vs. EC naproxen: 3.35 vs. 0.87 (p<0.001) in study 301 and 1.88 vs. 0.47 (p=0.003) in study 302. The OTE-DP results showed 45.6% on VIMOVO reporting positive change at month six vs. 27.8% on EC naproxen in study 301 (P<0.001) and 42.9% taking VIMOVO vs. 34.4% taking EC naproxen in study 302 (p=0.017).1
In addition to these measurements, the proportion of patients discontinuing due to UGI adverse events, including duodenal ulcers, (UGI AE/DU) was assessed for VIMOVO vs. EC naproxen in studies 301 and 302. The rates of discontinuation due to UGI AEs/DU for VIMOVO and EC naproxen respectively were 3.2% vs. 12.0% (p<0.001) in study 301 and 4.8% vs.
11.0% (p=0.009) in study 302.1
“Up to 60 percent of osteoarthritis patients will suffer from gastrointestinal side effects related to NSAIDs,2 demonstrating a need for treatment with decreased gastric side effects,” said Mark Sostek, M.D., F.A.C.G. and A.G.
A.F., Global Medical Sciences Director, AstraZeneca.
VIMOVO is a fixed-dose combination of enteric-coated naproxen,
non-steroidal anti-inflammatory drug (NSAID) and immediate release esomeprazole, a proton pump inhibitor (PPI), under investigation for the treatment of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in patients who are at risk of developing NSAID-associated gastric ulcers.
Commonly reported treatment emergent adverse events (experienced by ≥10%
patients in either treatment group from either study) included erosive gastritis, gastritis, dyspepsia and erosive duodenitis. In PN400-301
(n=434), 21% patients taking VIMOVO experienced erosive gastritis, as compared to 38% taking EC naproxen. Among patients taking VIMOVO, 18%
experienced gastritis, as compared to 13% taking EC naproxen, and 17% of the patients reported dyspepsia, as compared to 30% taking EC naproxen. Two percent of patients taking VIMOVO experienced erosive duodenitis as compared to 14% taking EC naproxen. In PN400-302 (n=420), incidences of erosive gastritis were reported by 18% of patients taking VIMOVO, as compared to 39% taking EC naproxen. Sixteen percent of patients taking VIMOVO experienced gastritis, as compared to 15% taking EC naproxen; 20%
patients taking VIMOVO reported dyspepsia, as compared to 23% taking EC naproxen. Two percent of patients taking VIMOVO experienced erosive duodenitis as compared to 10% taking EC naproxen.3
PN400-301 and PN400-302 were 6-month, Phase III, randomized, double-blind,
controlled, multi-center clinical trials that together enrolled approximately 800 H. pylori-negative adults with OA, RA, AS, or any other condition that required daily NSAID therapy and were at risk of ulcers. Subjects in each study were randomized to receive either VIMOVO/E20
(enteric-coated naproxen 500 mg/IR esomeprazole 20 mg) tablets twice-daily or EC naproxen 500 mg twice-daily, over a six-month treatment period.
Subjects underwent upper endoscopies at baseline and at one, three, and six months.3
On August 31, 2009, the US Food and Drug Administration (FDA) informed AstraZeneca and POZEN Inc. that it had accepted the New Drug Application
(NDA) for VIMOVO, submitted on June 30, 2009. AstraZeneca submitted a Marketing Authorization Application (MAA) to the European Union via the Decentralized Procedure for VIMOVO on October 16, 2009.
VIMOVO is an investigational product under co-development by AstraZeneca and POZEN Inc. that combines enteric-coated naproxen (an NSAID) with immediate release esomeprazole, a proton pump inhibitor (PPI). VIMOVO is under investigation for the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis in patients who are at risk of developing NSAID-associated gastric ulcers.
Osteoarthritis (OA) is a degenerative joint disease caused by the breakdown and eventual loss of the cartilage of one or more joints. Osteoarthritis is the most common form of arthritis and the most common cause of chronic pain, affecting nearly 151 million individuals worldwide,4 and impacting approximately 18% of women and 9.6% of men aged 60 and above.5 A combination of factors can contribute to osteoarthritis, including being overweight, aging, joint injury or stress,
heredity and muscle weakness.6 Osteoarthritis commonly affects the hands,
feet, spine or large weight-bearing joints, such as the hips and knees.7
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic disease, mainly characterized by inflammation of the lining, or synovium, of the joints. It can lead to long-term joint damage, resulting in chronic pain, loss of function and disability.8 RA affects approximately 1.3 million Americans.9
About Ankylosing Spondylitis
Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily causes pain and inflammation of the joints between the vertebrae of the spine and the joints between the spine and pelvis (sacroiliac joints). Ankylosing spondylitis may also cause inflammation and pain in other parts of the body as well.10
POZEN is a pharmaceutical company committed to developing therapeutic advancements for diseases and unmet medical needs where it can improve efficacy, safety and o/or patient convenience. POZEN’s efforts are focused primarily on the development of pharmaceutical products for the treatment of acute and chronic pain and other pain-related conditions. POZEN has development and commercialization alliances with AstraZeneca for VIMOVO™,
the proposed trade name for the proprietary fixed dose combination of naproxen with the proton pump inhibitor esomeprazole magnesium in a single tablet under development for conditions including osteoarthritis and rheumatoid arthritis in patients who are at risk for developing NSAID-associated gastric ulcers. The Company’s common stock is traded on The NASDAQ Stock Market under the symbol “POZN.” For detailed company information, including copies of this and other press releases, see the POZEN website: www.pozen.com.
AstraZeneca is engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and in the supply of healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with global healthcare sales of $ 31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory,
oncology and infectious disease medicines. In the United States,
AstraZeneca is a $13.5 billion dollar healthcare business.
For more information about AstraZeneca in the US or our AZ&Me™
Prescription Savings programs, please visit: www.astrazeneca-us.com.
Sandra Heinig, AstraZeneca (Global): 302-885-1084
Shannon Oates-Rivera, AstraZeneca (US): 302-886-5854
Alissa Maupin, POZEN: 973-635-6669 ext. 127
Heidi Lorman, POZEN: 973-635-6669 ext. 126
1. PN 400 Significantly Improves Upper Gastrointestinal Tolerability Compared with Enteric-Coated Naproxen Alone in Patients Requiring Chronic NSAID Therapy: Results from Two Prospective, Randomized, Controlled Trials.
Goldstein, Hochberg, Fort, Crawley, Sostek
2. American College of Gastroenterology. “Understanding GI Bleeding.”
http://www.acg.gi.org/patients/gibleeding/index.asp#compl. Accessed September 2009.
3. PN 400 Significantly Reduces the Incidence of Gastric Ulcers Compared with Enteric-Coated Naproxen in Patients Requiring Chronic NSAID Therapy Regardless of Low-Dose Aspirin Use: Results from Two Prospective,
Randomized Controlled Trials. Goldstein, Hochberg, Fort, Zhang, Sostek.
Department of Medicine, University of Illinois at Chicago, Chicago, IL,
USA; University of Maryland School of Medicine. POZEN
4. Global Burden of Osteoarthritis in the year 2000, (Symmons, Mathers,
Pfleger, 2006), Global Burden of Disease 2004.
5. World Health Organization. Chronic Rheumatic Conditions Fact Sheet.
http://www.who.int/chp/topics/rheumatic/en/. Accessed September 2008.
6. Mayo Clinic. Osteoarthritis: Causes.
Accessed February 2009.
7. American College of Rheumatology. Osteoarthritis.
http://www.rheumatology.org/public/factsheets/diseases_and_conditions/osteoarthritis.asp Accessed February 23, 2009.
8. Mayo Clinic. Rheumatoid Arthritis. Definition.
http://www.mayoclinic.com/health/rheumatoid-arthritis/DS00020. Accessed October 2009.
9. American College of Rheumatology. Patient Education. Rheumatoid Arthritis.
Accessed September 2009.
10. Mayo Clinic. Ankylosing Spondylitis. Definition.
http://www.mayoclinic.com/health/ankylosing-spondylitis/DS00483. Accessed September 2009.