The FINANCIAL -- AstraZeneca (NYSE: AZN) and POZEN Inc. (NASDAQ: POZN) on October 28 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. 

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