The first nitric oxide compounds from Nicox could be on the market in 2004, according to Mr Michele Garufi, the company's chief executive.
Nicox is a French development-based company which adds nitric oxide (NO) to established drugs. Speaking to The Journal on March 2, Mr Garufi said that Nicox currently had several drugs in clinical trials.
He said that the addition of nitric oxide could result in a compound which avoided the potential side effects of the established drug. For example, in NO-non-steroidal anti-inflammatory drugs (NO-NSAIDs), pain relief was provided by the NSAID portion while gastrointestinal side effects were "avoided" because the nitric oxide protected the gastric mucosa, so cancelling out the NSAIDs negative effect on prostaglandins. HCT-1026, a NO-derivative of flurbiprofen, was in trials for three indications. Following a demonstration of the drug's gastrointestinal safety in a phase I trial of 20 volunteers, all NO-NSAIDs for use in pain and inflammation had been licensed to Astra Zeneca for further development.
The addition of nitric oxide could also result in a therapeutic action of its own, said Mr Garufi. HCT-1026 was in clinical trials for Paget's disease, where the NO portion had been shown to be active in inhibiting the release of osteoclasts (a process seen in bone destruction). HCT-1026 was also being assessed for urinary incontinence (in phase II clinical trials) and as a topical application for inflammatory dermatological conditions.
NCX-4016 was a nitro-aspirin derivative being tested for cardiovascular use. Nicox was currently investigating the best formulation for the product and was hoping to go into partnership with another company to enter phase II trials next year, said Mr Garufi. NO-steroids, NO-salbutamol and NO-paracetamol were also being investigated.
Mr Garufi said that Nicox was screening a variety of drugs to see where adding NO would enhance the parameters of the established drug. However, there were some drugs to which it could not be attached. There had been problems in scaling up the production of an NO-mesalazine compound because the presence of the nitric oxide and the amino group of the mesalazine gave a potential for explosion.
Mr Garufi emphasised that the nitrate plasma levels from NO-derivatives were well below those recommended by the World Health Organisation and that no safety problems had been seen in clinical trials.