France’s NicOx has circumvented what could have been a major obstacle en route to winning approval for its lead drug naproxcinod (HCT 3012) in Europe, after winning agreement from the regulatory authorities that a major, long-term cardiovascular safety study will not be required.
Ongoing debate about the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) – including naproxcinod’s parent compound naproxen – has led to speculation that the European Medicines Agency might ask for a stringent safety study before giving a green light to NicOx’ product.
Instead, the company has proposed a plan to create a pre-approval database, in accordance with guidelines drawn up by the joint regulator-industry International Conference on Harmonisation (ICH) project, which will look at data from the clinical trials programme for naproxcinod.
NicOx is conducting three Phase III trials of the drug in osteoarthritis of the hip and knee and, with the need for a long-term safety study taken out of the equation, remains on track to file for approval of the drug in early 2009.
In addition to the more general concerns about the risk of heart attacks and stroke with conventional NSAIDs – which have arisen on the back of the withdrawal of Merck & Co’s COX-selective Vioxx (rofecoxib) from the market in 2004 - there is growing evidence that NSAIDs can cause elevations in blood pressure in susceptible individuals. Naproxen itself carries a warning on its label that it can impair the effects of blood pressure-lowering drugs.
Part of NicOx’ Phase III programme for naproxcinod is designed to show it has no detrimental effect on blood pressure, and data will be collected prospectively from all Phase III trials to try to demonstrate that quality.