July 11, 2005 01:00 ET

Clinical Trial Shows Promise With NicOx Nitric Oxide-Donating Compound in Bone Disease

SOPHIA ANTIPOLIS, FRANCE -- (MARKET WIRE) -- July 11, 2005 -- ( NicOx S.A. (Eurolist: NICOX) today announced that it has obtained positive results from a pilot phase II study for HCT 1026 in osteopenia (patients with low bone density who are at risk of osteoporosis), which showed a significant reduction in bone resorption markers following treatment. The trial reached its primary endpoint, with 24% of patients achieving a response (p < 0.001). HCT 1026 is a nitric oxide-donating derivative of flurbiprofen. These results demonstrate the potential utility of nitric oxide-donation in treating bone disorders and NicOx is keen to initiate a research project to identify lead compounds for clinical development in this therapeutic area.

Osteoporosis is caused by the deterioration of bone tissue and is an extremely common condition in the elderly. The disease often progresses painlessly until a spine or large-bone fracture occurs, resulting in a dramatic reduction in mobility and quality of life for the patient. The scale of the public health problem posed by osteoporosis and the poor patient compliance seen with existing drugs underlines the need for new drug therapies with increased activity and improved safety and tolerability profiles.

Giancarlo Isaia, Professor of Internal Medicine at the University of Turin and Principal Investigator of the trial, commented: "I was very satisfied to lead this phase II trial for a nitric oxide-donating compound in osteopenia. There is an increasing body of scientific evidence that nitric oxide plays an important role in bone renewal and repair and that a pharmacological approach involving nitric oxide-donation could help correct dysfunctional bone metabolism. This trial for HCT 1026 was preliminary in nature and followed a surrogate marker of the disease but the results are encouraging as they provide the first clinical data showing potential for NicOx' nitric oxide-donating technology in this important area."

Trial Design and Results

The trial was an open label, non-placebo controlled, pilot study that enrolled female patients with low bone mineral density and a high bone turnover (see NOTE 1), who had experienced menopause in the last 5 years. HCT 1026 was administered at 100 mg, twice daily, for 6 months. The objective of the trial was to evaluate the ability of HCT 1026 to positively affect bone turnover, by following associated biochemical markers (see NOTE 2). In order for the trial to meet its primary endpoint, at least 20% of patients needed to achieve a response (defined as a greater than or equal to 40% decline in the serum bone resorption marker CTX after 6 months of treatment). The primary endpoint was met, with 5 out of 21 evaluable patients (24%) experiencing a response (p < 0.001). The trial also met a secondary endpoint, based on the decrease of another urinary bone resorption marker NTX, with 6 out of 24 evaluable patients (25%) achieving a response after 6 months (p < 0.001). HCT 1026 was generally well tolerated in the trial.

HCT 1026 is in clinical development for the treatment of Alzheimer's disease and NicOx is focused on confirming the potential of the compound in this indication, following strong preclinical and phase I data (see press releases of April 14, 2004 and May 15, 2003). A number of the pharmacological properties of HCT 1026, including the apparent potential of the compound to reduce bone loss and its improved gastrointestinal tolerability profile compared to flurbiprofen, its parent compound, could make the product particularly attractive for use in the elderly who are suffering, or at risk from Alzheimer's disease and who are also prone to osteoporosis and sensitive to gastrointestinal damage. In this trial, NicOx used HCT 1026 as a test compound for osteoporosis, to confirm the activity of nitric oxide-donation in this area. Therefore, it is not expected that further clinical trials will be conducted with HCT 1026 in osteoporosis, other than to generate supporting data for the Alzheimer's disease indication.

Damian Marron, Vice President of Business Development, at NicOx, commented: "The clinical results announced today indicate the potential for NicOx' nitric oxide-donating technology to be useful in bone diseases and builds on the solid scientific rationale for this approach based on the important role of nitric oxide in healthy bone metabolism. NicOx will now initiate discussions with potential partners to apply this technology to other agents known to have pharmacological activity in the bone. We believe this approach could lead to the identification of clinical development candidates for osteoporosis and related bone diseases with increased activity over HCT 1026.

"NicOx' strategy is to focus its in-house research and development in the therapeutic areas of inflammation and cardiovascular disease. Therefore, NicOx is actively seeking a partner to advance HCT 1026 into phase II clinical trials in Alzheimer's disease."


- Inclusion criteria - patients needed to have: a bone mineral density between -1 and -2 standard deviations from the norm at the lumber spine (technically osteopenia; osteoporosis is defined as greater than or equal to -2.5 standard deviations from the norm) and a high bone turnover rate, as indicated by a free urine deoxy pyridinoline (u-DPD) / creatinine ratio greater than or equal to 8.5 mmol/mol (the u-DPD to creatinine ratio is considered to be an accurate measure of bone turnover).

- Exclusion criteria: bone diseases other than osteoporosis; receipt of corticosteroids or an existing osteoporosis treatment within the previous 6 months, or NSAIDs within the previous 14 days.


- Type I collagen makes up over 90% of the organic matrix of bone. The bone resorption markers CTX (C-terminal cross-linked telopeptide of type I collagen) and NTX (N-terminal cross-linked telopeptide of type I collagen) are generated from the degradation of bone by osteoclasts (cells which break down bone). These two biochemical markers are routinely used for monitoring the efficacy of anti-resorptive therapy for osteoporosis because clinical studies have demonstrated that a decrease in their concentration correlates with an increase in bone mineral density. The levels of NTX were measured in the urine and therefore its concentration was normalized by expressing it as a ratio of the creatinine concentration. An NTX response was defined as a greater than or equal to 40% decrease in this parameter, from baseline.

NicOx S.A. is an emerging pharmaceutical company involved in the research and development of nitric oxide-donating drugs with superior efficacy and safety profiles in the inflammation, pain and cardiovascular therapeutic areas.

NicOx seeks to commercialize its products through partnerships and co-development agreements where it maintains future marketing rights for specialist products.

NicOx S.A. (Bloomberg: COX:FP, Reuters: NCOX.LN), headquartered in Sophia-Antipolis, France, is a public company listed on the Eurolist of Euronext Paris (segment: Next Economy).

The elements included in this communication may contain forward-looking statements subject to certain risks and uncertainties. Actual results of the company may differ materially from those indicated in the forward-looking statements because of different risks factors described in the company's document de reference.

Contact Information