Novartis Pharma AG announced that results from a trial showed that Prexige (lumiracoxib), the structurally distinct and most selective COX-2 inhibitor, demonstrated a significant 79 per cent reduction in the incidence of upper gastrointestinal (GI) ulcer complications without compromising cardiovascular (CV) safety.

The results were the basis for two papers published online in The Lancet on the findings of the landmark Target (Therapeutic Arthritis Research & Gastrointestinal Event Trial of lumiracoxib) study that further confirmed the safety benefit of Prexige.

"The excellent GI and CV safety profile of Prexige demonstrated by the positive results of Target shows a favorable benefit/risk ratio for Prexige, even at multiples of the normal chronic dose. These findings may be linked to the different chemical and pharmacokinetic properties of Prexige which is the most selective COX-2 inhibitor," said Joerg Reinhardt, Head of Development, Novartis Pharma AG.

"With up to an estimated 16,500 GI-related deaths in the US each year, these convincing data from 18,325 patients with osteoarthritis (OA) builds on the body of evidence suggesting that Prexige is effective while offering substantial GI safety benefits. Target fully supports the approved label in the UK and builds a strong basis for the ongoing European Mutual Recognition Process (MRP), which was recently started," Reinhardt said.

Target is the largest GI safety outcomes study performed to date and clearly demonstrates beneficial results specifically for the GI safety of Prexige. The Target data demonstrate that in patients not taking low-dose aspirin, Prexige had an overall statistically significant reduction of 79% versus the two comparator NSAIDs (non-steroidal anti-inflammatory drugs) naproxen and ibuprofen in the incidence of definite or probable upper GI ulcer complications (p<0.0001). Prexige significantly reduced the incidence of upper GI ulcer complications in those patients not taking aspirin by 83% versus ibuprofen and by 76% versus naproxen. For the overall population (patients taking and not taking low dose aspirin), Prexige significantly reduced the incidence of upper GI ulcer complications by 66% versus the two NSAIDs. For the smaller subgroup of patients taking aspirin, a numerical trend of 21% decrease of ulcer complications in favor of Prexige was observed compared to the NSAIDs.

"Target was a very well-designed study and therefore yields robust results for Prexige, demonstrating an up to four-fold reduction in the incidence of GI ulcer complications compared to NSAIDs," said Chris Hawkey, Professor of Gastroenterology and Co-director of the Institute of Clinical Research, University of Nottingham and Chairman of the GI committee during the TARGET trial. "The benefit demonstrated by Prexige has not been shown by any other selective COX-2 inhibitor," he added.

In addition to GI tolerability, Target investigated CV safety. Prexige did not increase the CV risk (defined as the combined Anti-Platelet Trialist Collaboration [APTC] endpoint) compared to the two NSAIDs. The APTC endpoint included confirmed or probable non-fatal myocardial infarction (MI) including silent MI (ECG-detected), non-fatal stroke (ischemic or hemorrhagic) and cardiovascular death. For the APTC endpoint, no significant difference between Prexige and the comparator NSAIDs was observed in the overall population, or in the populations investigated separately for those taking or not taking low-dose aspirin. Furthermore, there was no significant difference in the incidence of MIs, congestive heart failure and other thrombotic events observed in the overall population groups studied between Prexige and naproxen or ibuprofen, the release added.

"Target demonstrates that Prexige has a CV profile similar to conventional NSAIDs with a more favourable blood pressure profile. These very important results show that Prexige offers GI benefits to patients without compromising their CV safety," Dr. Michael Farkouh, Director of the Cardiac Care Unit at New York University Medical Centre and Chair of the Target Cardio-Cerebrovascular adjudication committee said adding, "In Target, we found no difference in MIs, stroke or any of the other CV endpoints investigated between Prexige and ibuprofen or naproxen."

For the pre-specified endpoint combining serious GI and CV events, Prexige at up to four times the recommended dose for OA showed a significant 35% reduction (p=0.001) versus the NSAID groups. Importantly, mean changes in systolic and diastolic blood pressure from baseline for patients taking Prexige were significantly smaller (p=0.0001) than for those taking NSAIDs (systolic +0.4 mmHg vs. +2.1 mmHg respectively; diastolic -0.1 mmHg vs. +0.5 mmHg respectively).

Prexige was developed for the treatment of the signs and symptoms of arthritis and management of pain. Prexige is the most selective cyclooxygenase-2 (COX-2) inhibitor with a non-sulfur containing structure distinct from existing selective COX-2 inhibitors. Prexige has proven efficacy in an extensive phase III clinical trial program demonstrating rapid onset in acute pain with 400mg once daily (od) for short term use and efficacy in OA with 100mg od (data on file) and 200mg od and rheumatoid arthritis at 200mg od.