Novartis said it has received a "not approvable" letter from the US Food and Drug Administration (FDA) for its COX-2 inhibitor Prexige (lumiracoxib) as a once-daily treatment for patients suffering from osteoarthritic pain.

The FDA's response came despite a clinical trial database for Prexige that comprises approximately 40,000 patients and is one of the largest bodies of evidence for any drug in this class.

In particular, results of the target study involving more than 18,000 patients showed Prexige reduced the incidence of serious upper gastrointestinal complications by 79 per cent compared to two widely-used non-steroidal anti-inflammatory drugs (NSAIDs) in patients not taking aspirin.

Target also showed the drug was associated with significantly smaller increases in blood pressure than the NSAIDs naproxen and ibuprofen, with no significant difference in cardiovascular events such as heart attack or stroke, the company said.

"Many patients cannot tolerate the gastrointestinal side effects associated with NSAID pain treatments, such as those suffering from ulcers or who are being treated with anti-coagulants like warfarin. We believe Prexige remains an important therapy for appropriate patients with osteoarthritic pain, and we will continue discussions with the FDA," said James Shannon, managing director, global head of development, Novartis Pharma AG.

At the FDA's request, Novartis submitted clinical data on the liver profile of the proposed 100 mg once-daily dose studied over 12 months of therapy. The results showed 0.85 per cent of patients had elevations of the liver enzymes aspartate amino transferase (AST) and alanine amino transferase (ALT) of greater than "three times the upper limit of normal," which is similar to levels observed with currently available NSAIDs, the company press release said. There were also no cases of jaundice or hepatic failure on Prexige 100 mg once-daily dosing in the clinical development program. Despite this data, the FDA deemed Prexige not approvable.

According to the company press release, the FDA noted in its response that it remained open to exploring the use of this medicine in patients where Prexige would provide an acceptable benefit-to-risk balance. This group could include patients with a higher incidence of gastrointestinal complications, including those suffering from ulcers or being treated with anticoagulants.

Prexige is currently approved in more than 50 countries. An alternative trade name for this medicine has been submitted for US regulatory approval.