Novartis offers Vioxx alternative

Since the recall of Vioxx, a blockbuster drug (meaning sales of $1 billion or more), Merck's competitors have rushed to offer alternatives. After all, it is an opportunity of a lifetime. Recently released data suggests that most of the market share has now been grabbed by Celebrex and Bextra. Another study released yesterday shows that while Celebrex belongs to the same category as Vioxx (Cox-2 inhibitors), Vioxx was way too dangerous a drug. This will definitely help Celebrex. (Related article: Vioxx alternatives may not be totally safe)

At the same time, there are reports that a lot of other Vioxx alternatives are being proposed. New data from two studies provide strong evidence that the selective COX-2 inhibitor Prexige (lumiracoxib), manufactured by Novartis, taken daily at 100 mg offers reduced pain intensity while improving the functional status of patients' osteoarthritis (OA) of the knee. These data were presented at the Osteoarthritis Research Society International annual meeting in Chicago on December 4.

The data shows that over the 13-week study Prexige 100 mg once daily significantly reduced OA pain intensity in the target knee compared to placebo and was comparable to celecoxib 200 mg once daily. In the first study, Prexige demonstrated significant improvements in pain intensity from the first measurement at Week 2 with a significant reduction of 42% in pain intensity at study end (p<0.01 vs placebo).

A similar decrease was observed in the second study with significant improvements throughout the study and a 38% decrease in pain intensity by study end (p<0.001 vs placebo). Throughout the study Prexige and celecoxib demonstrated significant improvements in functional status in both studies compared with placebo, with no statistically significant difference observed between active treatment groups.

In both trials, the number of patients discontinuing treatment due to adverse events, including serious adverse events, was similar between placebo and the active treatment groups. Furthermore, no significant difference was observed between all treatment groups for the incidence of liver enzyme elevations, defined as alanine aminotransferase/aspartate amino-transferase levels above three times the upper limit of normal. In the first study enzyme elevations with Prexige were 0.2%, celecoxib 0.5% and placebo 0.5%, and Prexige/celecoxib 0.3% and placebo 0.0% in the second study. These data reinforce the existing body of evidence showing a favorable safety and tolerability profile for Prexige.

Though data regarding gastrointestinal (GI) and cardiovascular (CV) adverse events were not evaluated separately in these trials, results from the landmark TARGET (Therapeutic Arthritis Research & Gastrointestinal Event Trial of lumiracoxib), which were published in August 2004 in The Lancet, demonstrated a significant 79% reduction in the incidence of upper gastrointestinal (GI) ulcer complications without compromising cardiovascular (CV) safety. The TARGET trial demonstrated that Prexige has a cardiovascular profile similar to conventional non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and naproxen.

The two similarly designed 13-week, randomized, placebo and active-controlled trials compared Prexige 100 mg once daily, Prexige 100 mg once daily with a loading dose of 200 mg once daily for the first two weeks and celecoxib 200 mg once daily to placebo. Both trials were designed using three co-primary efficacy variables including functional status assessment criteria: OA pain intensity in the target knee, patient's global assessment of disease activity and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) questionnaire. Improvement in patient's functional status was further assessed using the OMERACT-OARSI functional status criteria.

Novartis has filed applications for regulatory approval throughout the world based on data from more than 40 pre-clinical and clinical studies in OA, rheumatoid arthritis, acute pain and primary dysmenorrhea involving more than 31,000 adult patients around the world (including TARGET). In addition to the United Kingdom, Prexige has been approved in 21 countries to date, including Australia, New Zealand and several countries in Latin America, including Argentina, Brazil and Mexico. On November 30, 2004, Novartis announced that it had temporarily withdrawn the dossier for Prexige from the Mutual Recognition Procedure in Europe to await the outcome of the EMEA cardiovascular safety review of all COX-2 inhibitors.

Recommended article: Non Cox-2 alternatives to Vioxx for pain relief