French company NicOx has started a Phase III trial of a drug for osteoarthritis that could, if successful, elevate the company into the big league of European biopharmaceutical firms.
The drug under study is HCT 3012, a derivative of the non-steroidal anti-inflammatory drug (NSAID) naproxen that could offer the benefits of the parent compound without its negative effects on blood pressure.
There is growing evidence that NSAIDs can cause elevations in blood pressure in susceptible individuals, and naproxen itself carries a warning on its label that it can impair the effects of blood pressure-lowering drugs.
If HCT 3012 lacks this effect of blood pressure, it could emerge as the treatment of choice for people with osteoarthritis, particularly the 40% of patients who are already taking blood pressure medications, said NicOx. The compound counteracts the blood pressure effects by donating nitric oxide, which lowers blood pressure by relaxing blood vessels.
The Phase III trial is designed to demonstrate that HCT 3012 is superior to placebo and as effective as naproxen in relieving the signs and symptoms of osteoarthritis, in addition to showing that HCT 3012 has no detrimental effect on blood pressure.
"We believe HCT 3012 has the potential to play a major role in the anti-inflammatory market," said Michele Garufi, chairman and CEO of NicOx. "Our view is that HCT 3012 could become the reference drug for millions of osteoarthritis patients with hypertension if this Phase III programme is successful.”
However, a lot of the excitement surrounding HCT 3012 comes from the possibility that it could have broader safety advantages over other NSAIDs. A study reported at the American Heart Association conference earlier this year suggested blood pressure elevations are also seen with COX-2 inhibitors, and could be behind the link to heart attacks that led to the withdrawal of one of the top drugs in this class, Merck & Co’s Vioxx (rofecoxib) last year.
The furore surrounding this withdrawal caused the US Food and Drug Administration to tighten up labeling across the board for COX-2 inhibitors and traditional NSAIDs earlier this year, to include a warning saying that “NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal.”
This means HCT 3012 could step forward and fill the void left by Vioxx, as well as providing a safer alternative to those NSAIDs and COX-2 inhibitors that remain on the market.
In a report released late last month, consultancy firm Decision Resources said the market for arthritic pain treatments will sustain extensive losses in 2005 followed by a 5% annual average decline through 2009. However, from 2009 to 2014, the market will rebound to approximately 6% annual growth due to the arrival of new therapies, including HCT 3012, it predicts.
NicOx said an additional trial of HCT 3012 is expected to start during the first half of 2006, which will employ ambulatory blood pressure monitoring to look at the blood pressure profile of HCT 3012 and naproxen over a 24-hour period in people with high blood pressure.