Emerging Drug List — Lumiracoxib for Pain Management

Emerging Drug List CANADIAN COORDINATING OFFICE FOR HEALTH LUMIRACOXIB FOR PAIN MANAGEMENT TECHNOLOGY ASSESSMENT

NO. 46 JUNE 2003 Generic (Trade Name): Lumiracoxib (Prexige)

Manufacturer: Novartis Pharmaceuticals

Indication: For pain management, arthritis and menstrual cramps.1

Current Regulatory Lumiracoxib is currently not available in Canada. The product is under investigation and Status: no availability date has been established (Patricia Bosse, Novartis Pharmaceuticals Canada Inc., Dorval, PQ: personal communication, 2003 Mar 14).

In November 2002, Novartis announced that it had filed applications with both the American and European regulators to gain authority to launch their product.1 An anticipated date for launch in these markets is some time in 2003; although at one point there was speculation that launch may be delayed awaiting the results of clinical studies currently underway, pushing the possible marketing date to 2005.2

Description: Lumiracoxib is a nonsteroidal anti-inflammatory (NSAID) with relative selectivity for the cyclo-oxygenase COX2 enzyme. It is rapidly absorbed after oral administration with maximum concentrations achieved after two to three hours. The elimination half-life is approximately three to six hours; however it does possess kinetic properties allowing for once daily administration.3

Current Treatment: Other NSAIDs available in Canada include the acetic acids [diclofenac (Voltaren - Novartis, generics), etodolac (Ultradol - Procter & Gamble, generics), indomethacin (Indocid - Merck Frosst, generics), ketorolac (Toradol - Roche), sulindac (generics), mefenamic acid (Ponstan - Pfizer, generics), nabumetone (Relafen - GSK)], propionic acids [flurbiprofen (Ansaid - Pharmacia, generics), ibuprofen (Motrin - McNeil, generics), ketoprofen (Orudis, Oruvail - Aventis, generics), naproxen (Naprosyn - Roche, generics)], and salicylates (aspirin - generics). NSAIDS with relative COX2 selectivity include celecoxib (Celebrex - Pharmacia), rofecoxib (Vioxx - Merck Frosst), valdecoxib (Bextra - Pharmacia), etoricoxib (Arcoxia® - Merck Frosst), and meloxicam (Mobicox - Boehringer Ingelheim).4,5

Cost: As this product in currently under investigation, no cost information is available at this time.

Evidence: The clinical data available at this time are sparse, and mostly consist of trials in abstract form. In 2002, data on lumiracoxib were presented at the EULAR (European League Against Rheumatism) annual conference and several scientific abstracts are available online at www.eular.org/eular2002/index.cfm.

The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca) Emerging Drug List CANADIAN COORDINATING OFFICE FOR HEALTH LUMIRACOXIB FOR PAIN MANAGEMENT TECHNOLOGY ASSESSMENT

Schnitzer et al. randomized 583 patients with osteoarthritis of the hip or knee to one of four doses of lumiracoxib (50, 100, 200 mg bid or 400 mg daily), diclofenac 75 mg bid or placebo for a period of four weeks. Pain intensity, as judged by visual analog scale (VAS) with all doses of lumiracoxib was considered statistically superior to placebo (p<0.05, using VAS mean vs. baseline) at weeks one, two and four. At weeks one and two, however, diclofenac was considered statistically superior to lumiracoxib twice daily dosing regimens (p<0.05). At week one the lumiracoxib 400 mg daily arm was considered statistically superior to the lumiracoxib 50 or 100 mg bid arms.6 Moore et al. presented data at EULAR indicating responder rates, defined as a 20% reduction in pain intensity (VAS), were considered comparable between diclofenac 75 mg bid (n=70/93) and lumiracoxib 400 mg once daily (n=72/98).7

The data from the TARGET (Therapeutic Arthritis Research and Gastrointestinal Event Trial) trial are eagerly anticipated. This international study involving over 18,000 patients with osteoarthritis compares lumiracoxib 400 mg daily with ibuprofen and naproxen. This study will examine both comparative efficacy and gastrointestinal tolerability, along with a secondary endpoint of cardiovascular events which is spawning much interest.3

Adverse Effects: Overall, the data available to date suggest that lumiracoxib could be well tolerated. In a small sampling of healthy subjects (n=60), after seven days of treatment with lumiracoxib 200 mg bid, naproxen 500 mg bid and placebo, 0, 65 and 5% of patients were observed to have gastroduodenal erosions on endoscopy. No changes in laboratory parameters were noted.8 In a three month study that compared lumiracoxib (200 and 400 mg daily) to ibuprofen (800 mg tid) and celecoxib (200 mg daily), gastroduodenal ulcers were noted on endoscopy in 4.3, 4.0, 15.7 and 3.2% of osteoarthritis patients (n=1,011), respectively. Cessation of treatment due to adverse events was higher in the ibuprofen group relative to lumiracoxib and celecoxib (12.7% vs. 5-6.8%).9

Commentary: To date, there are no available data to suggest lumiracoxib possesses any advantages in terms of efficacy when compared to other NSAIDs. Likewise, it is not possible to say it has a better gastrointestinal tolerability profile than other well-tolerated NSAIDS already available.

Data from the TARGET trial will provide much needed information about the toxicity of this new NSAID, relative to naproxen and ibuprofen. These data may also shed more light on the increasingly important issue of the potential harm from drugs with increased COX2 affinity.

References: 1. Novartis files for approval to market Prexige in both America and Europe. ILF News 2002 Nov 27. Available: http://eu.ilfnews.com/storyID=370112701.htm (accessed 14 Mar 2003).

2. Reuters. Novartis pain drug data get mixed reviews. Ledger-Enquirer [newspaper online] 2002 Jun 13.

Available: www.ledger-enquirer.com/mld/ledgerenquirer/3459027.htm (accessed 14 Mar 2003). 3. Stichtenoth DO, Frolich JC. The second generation of cox-2 inhibitors: what advantages do the newest offer? Drugs 2003;63(1):33-45. 4. Therapeutic Products Programme, Health Canada. Notices of Compliance (NOC): drugs [database online]. Ottawa: Health Canada; 2003. Available: www.hc-sc.gc.ca/hpb- dgps/therapeut/htmleng/noc_drugs.html (accessed 2003 Mar 19). 5. Setter SM, Baker DE. Nonsteroidal anti-inflammatory drugs. In: Anderson PO, Knoben JE, Troutman WG, editors. Handbook of clinical drug data. 10th ed. New York: McGraw-Hill Medical Publishing Division; 2002. p. 26-30. 6. Schnitzer TJ, Geusens P, Hasler P, Patel SK, Poor G, Senftleber I, et al. Efficacy and safety of COX189 in osteoarthritis: a multi-national study [abstract]. Arth Rheumat 2000;43:S336. 7. Moore A, Della Casa Alberighi O, Gitton X, Sloan V, Gimona A. Responder rate of COX 189 in osteoarthritis: a multi-national study [abstract]. EULAR 2002: Third Annual European Congress of Rheumatology; 2002 Jun 12-5; Stockholm. Abstract THU0265. Available: http://mcic3.textor.com/cgi- bin/mc/printabs.pl?APP=eular2002SCIE- abstract&TEMPLATE=..%2F..%2Fdata%2Feular2002SCIE%2Fdel.html&keyf=1728&showHide=show (accessed 2003 Mar 20). 8. Rodorf C, Scott G, Blood P, Milosavljev S, Branson J, Kellet N, et al. Treatment of healthy subjects with cox189, a cox-2 selective inhibitor; endoscopic evidence for lack of gastro-duodenal erosions compared to non-selective NSAID. EULAR 2002: Third Annual European Congress of Rheumatology; 2002 Jun 12-5; Stockholm. Abstract THU0232. Available: http://mcic3.textor.com/cgi- bin/mc/printabs.pl?APP=eular2002SCIE- abstract&TEMPLATE=..%2F..%2Fdata%2Feular2002SCIE%2Fdel.html&keyf=0178&showHide=show (accessed 2003 Mar 20). 9. Hawkey CJ, Karateev D, Codreanu C, Dobronte Z, Gomez Reino J, Hopkinson N, et al. Improved upper gastrointestinal (UGI) safety and tolerability of new coxib, cox189 compared with ibuprofen in osteoarthritis patients. EULAR 2002: Third Annual European Congress of Rheumatology; 2002 Jun 12- 5; Stockholm. Abstract THU0226. Available: http://mcic3.textor.com/cgi- bin/mc/printabs.pl?APP=eular2002SCIE- abstract&TEMPLATE=..%2F..%2Fdata%2Feular2002SCIE%2Fdel.html&keyf=1691&showHide=show (accessed 2003 Mar 20).

This series highlights medical technologies that are not yet in widespread use in Canada and that may have a significant impact on health care. The contents are based on information from early experience with the technology; however, further evidence may become available in the future. These summaries are not intended to replace professional medical advice. They are compiled as an information service for those involved in planning and providing health care in Canada. These summaries have not been externally peer reviewed.

ISSN 1496-8398 (online only)

The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) is a non-profit organization funded by the federal, provincial and territorial governments. (www.ccohta.ca)