SOPHIA ANTIPOLIS, France, Sept. 6 /PRNewswire-FirstCall/ -- NicOx S.A. (Eurolist: NICOX) is today announcing the full details of the phase 3 clinical program it has designed to gain regulatory approval for naproxcinod (HCT 3012) for treating the signs and symptoms of osteoarthritis (OA) in the United States (US) and Europe. The plan consists of three phase 3 efficacy trials, the first of which is currently ongoing in knee OA in the U.S., with an additional, similarly designed knee OA study expected to start in the first quarter of 2007. This will be followed by the initiation of a hip OA trial in the third quarter of 2007. NicOx is also providing details of its recent interactions with regulatory authorities for naproxcinod. In addition, NicOx is providing new information on the clinical studies it plans to conduct to confirm naproxcinod’s superior blood pressure control and gastrointestinal safety and tolerability profile, compared to existing anti-inflammatory agents.
Summary of additional disclosures being made today:
* Initiation of an important new development program for NCX 6560, a nitric oxide-donating statin derivative with broadened activity for the treatment of high risk cardiovascular patients (see separate press release)
* New results from two clinical studies for NCX 4016, which support the rationale for developing this compound for the treatment of type 2 diabetes
* Disclosure that the first results from NicOx’ collaboration with Merck & Co., Inc. in the antihypertensive field will be presented at scientific conferences in the fall, including the American Heart Association (AHA)
* Announcement that Pfizer Inc anticipates filing an IND in the first quarter of 2007 for the development compound in glaucoma
Naproxcinod -- the first in a new class of anti-inflammatories with potential to become the drug of choice for OA
Naproxcinod is NicOx’ lead product, in phase 3 clinical development for the treatment of the signs and symptoms of OsteoArthritis. NicOx aims to develop naproxcinod as a novel, first-in-class anti-inflammatory product, with no detrimental effects on blood pressure and good gastrointestinal tolerability, which would consequently become the drug of choice for OA patients.
The phase 3 efficacy program for obtaining regulatory approval for naproxcinod in the US and Europe consists of the following three pivotal phase 3 studies:
* 301 study: a phase 3 clinical efficacy trial is currently ongoing for naproxcinod in patients with OA of the knee. The successful enrolment of 820 patients, as required by the protocol, was completed ahead of schedule and the trial has subsequently enrolled a further 98, due to investigators’ enthusiasm to include eligible patients. Results are anticipated in the fourth quarter of 2006. For details on the design of this study, please see the press release of December 20, 2005.
* 302 study: a second phase 3 study is planned to be initiated in the first quarter of 2007, with efficacy results anticipated in the first quarter of 2008. This study will enroll approximately 840 patients with knee OsteoArthritis. It will have a similar design to the ongoing 301 trial, being a double-blind, placebo and naproxen-controlled study, with three standard co-primary endpoints used to assess efficacy.
* 303 study: there will be a third phase 3 study in hip OsteoArthritis, which is scheduled to start in the third quarter of 2007, with results anticipated in the third quarter of 2008. This trial will also have the primary objective of assessing efficacy.
In addition, both of the knee OA trials (studies 301 and 302) have long term extensions which will provide a year or more of safety data. The safety dataset will exceed ICH guidelines by a large margin and the last of this data is expected to be available in the fourth quarter of 2008. Thus, the Company anticipates that regulatory submissions in the US and Europe may be submitted during the first quarter of 2009, subject to any additional requirements from regulatory authorities.
Update on NicOx’ ongoing dialog with regulatory authorities worldwide NicOx is also providing an overview of its ongoing dialog regarding naproxcinod with regulatory authorities in the US and European territories. Based on discussions with the US Food and Drug Administration (FDA) and regulatory authorities in the United Kingdom (UK) and Sweden, NicOx believes that its phase 3 plan, outlined above, will be adequate to satisfy current requirements in the US and European Union (EU) with regards to demonstrating the efficacy of naproxcinod for treating the signs and symptoms of OsteoArthritis.
The agencies in Sweden and the UK have also advised NicOx that under current EU requirements the safety of naproxcinod should be assessed according to the standard ICH guidelines, which implies that a long-term cardiovascular safety study would not be required to gain marketing authorization in these territories. NicOx has requested Scientific Advice on naproxcinod from the European Medicines Agency (EMA, the European Union’s central regulatory body).
Discussions with the FDA are continuing concerning the requirements for long-term safety data needed for the approval of naproxcinod in the US In August 2006, NicOx submitted documentation to the FDA regarding naproxcinod and COX inhibition and is awaiting the agency’s comments on this package.
Moreover, NicOx plans to validate a proposed development for Japan with the Japanese authority in the first quarter of 2007.
“The senior management of NicOx believes that the phase 3 efficacy plan we are presenting today for naproxcinod will allow us to gain an indication for treating the signs and symptoms of OA in the territories where we have held regulatory discussions,” commented Staffan Stromberg, Vice President of Drug Development at NicOx. “Our projected timings for regulatory submissions may be subject to revision, due to the possibility of new requests from regulatory agencies. Regarding our dialog with the FDA concerning potential requirements for long term safety data, we are working hard to help bring about a positive resolution of this issue and are encouraged by the nature of our two-way interaction.”
Marketing support studies aiming to confirm naproxcinod’s safety and tolerability advantages
Millions of people rely on non steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors as the only available drugs to treat chronic pain and inflammation associated with OA and a range of other serious conditions. Unfortunately these products are associated with a low but significant incidence of serious side effects, such as cardiovascular and gastrointestinal complications, which can be life threatening in some cases. The preclinical and clinical studies conducted to date suggest that naproxcinod possesses an improved blood pressure control and gastrointestinal safety and tolerability profile, compared to existing NSAIDs, due to nitric oxide donation. NicOx is today providing additional information on its plans to confirm these initial findings through clinical studies, in order to reassure patients of naproxcinod’s improved safety and tolerability and to support future marketing activities for the product.
* Blood pressure Patients’ blood pressure will be assessed during the phase 3 program (including the ongoing 301 study and the planned 302 and 303 studies) by using controlled office blood pressure measurements (OBPMs) during each visit to the treatment center. A predefined pooled analysis of the blood pressure data from these three studies is expected to be made in 2008, following the completion of the last trial.
An additional trial (the ABPM study -- see press release of May 4, 2006) is ongoing. This trial is designed to provide complementary data to the phase 3 program by recording the blood pressure of hypertensive subjects over 24 hours, using an automatic mobile device (ambulatory blood pressure monitoring, ABPM). Subject enrolment was successfully completed ahead of schedule in early August and results are anticipated in the fourth quarter of 2006.
* Gastrointestinal safety and tolerability NicOx plans to conduct a clinical endoscopy study with the objective of confirming the previous clinical findings that naproxcinod treatment results in less gastro-intestinal damage than naproxen (the 305 study). The study will be powered to show a statistically significant difference and is expected to start during 2007.
New clinical results supporting the rationale for developing NCX 4016 as an insulin sensitization agent for the treatment of type 2 diabetes
NicOx is disclosing new results from two clinical studies for its second lead compound, NCX 4016. The first results are from a sub-study of a previously announced trial in 40 type 2 diabetes patients and show that NCX 4016 led to increased glucose utilization after two weeks of treatment. The second study, in 12 healthy subjects with obesity, demonstrated a highly significant improvement in glucose uptake after 2-weeks of treatment with NCX 4016. These newly announced results support NicOx’ recent decision to initiate two clinical studies for NCX 4016 in type 2 diabetes patients (see press release of July 26, 2006).
* Results from a phase 2a sub-study in type 2 diabetes These new clinical results come from a sub-study within the phase 2a trial that was previously announced in a press release on March 1, 2005. The primary endpoint of this trial followed platelet activation, although the sub-study had the different objective of studying the effects of NCX 4016 on patients’ insulin levels and glucose utilization. Forty patients underwent a 4-hour hyperglycemic clamp procedure after 2 weeks of treatment with either: NCX 4016, NCX 4016 plus aspirin, aspirin alone or placebo (10 patients per group). The results of the sub-study reveal that during the last 30 minutes of the clamp insulin plasma levels were approximately 40% higher in the two groups that received NCX 4016, when compared to the groups which received aspirin only and placebo, most probably due to decreased insulin clearance.
During the clamp, glucose was infused at a variable rate in order to maintain plasma glucose levels at a steady state. The results indicate that the glucose infusion rate during the last 30 minutes of the clamp was approximately 50-60% higher in the two NCX 4016 treated groups, compared to the groups treated with aspirin alone and placebo, indicating increased glucose utilization.
* Results of a study in healthy volunteers with obesity NicOx is also presenting new data from an investigator led study, comparing NCX 4016 to placebo in 12 healthy volunteers with obesity. The subjects were administered NCX 4016 or placebo for 2-weeks, in a cross-over design, before undergoing a hyperglycemic clamp procedure. Subjects receiving NCX 4016 had a highly significant improvement in glucose uptake (p<0.001) and revealed a trend (p=0.06) for lower fasting blood glucose levels in comparison to subjects receiving placebo. Insulin resistance is often seen in people with obesity and NCX 4016 may have potential in preventing the development of type 2 diabetes in insulin resistant patients, although NicOx has no current plans to explore this as an indication for NCX 4016.
An update on ongoing alliances
Merck & Co., Inc. - development of nitric oxide-donating antihypertensive drugs
On March 21, 2006, NicOx announced a major new collaborative agreement with Merck & Co., Inc. to develop nitric oxide-donating antihypertensive agents using NicOx’ proprietary technology. The joint research program is focused on identifying lead candidates for development and is progressing well. The first results are scheduled to be presented at scientific conferences this fall. These results, in validated in vivo models of raised blood pressure, demonstrate that a NicOx-Merck compound was significantly better at lowering blood pressure than a widely used reference drug, after single and repeated oral dosing.
* The first presentation will be at The 60th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research in association with the Council on the Kidney in Cardiovascular Disease, on October 6, in San Antonio, Texas. * The second presentation will be on November 13 at the annual meeting of the American Heart Association (AHA) in Chicago.
Pfizer Inc -- development of nitric oxide-donating treatments for glaucoma and other eye disorders
NicOx and Pfizer Inc have two research and development collaborations ongoing, which are aimed at developing new nitric oxide-donating drugs for a range of ophthalmologic diseases. Both collaborations are progressing well and NicOx can disclose that Pfizer anticipates filing an IND for the first compound in development for glaucoma in the first quarter of 2007 (an IND, or Investigational New Drug application, is required to conduct clinical studies in the US). This development compound was selected in November 2005 and is covered by the Companies’ August 2004 agreement.
The Companies’ second collaboration is covered by the major new agreement that was signed by NicOx and Pfizer in March 2006, which granted Pfizer exclusive rights to apply NicOx’ proprietary nitric oxide-donating technology across the entire field of ophthalmology.
Michele Garufi, Chairman and CEO of NicOx, commented: “We are very pleased with the recent progress we have made in research and development, which has included the selection of two pre-clinical development compounds in the last twelve months, namely from our glaucoma program with Pfizer and from our exciting internal project focused on nitric oxide-donating statins, announced today. Our growing momentum in R&D is underlined by the fact that the number of patients under management in NicOx’ clinical trials has grown from 280 in 2005 to 1050 in 2006 and is expected to reach 2150 in 2007. We have already transformed NicOx through our efforts and are well on our way towards becoming an integrated Pharmaceutical Company.”
NicOx (Bloomberg: COX:FP, Reuters: NCOX.PA) is a product-driven biopharmaceutical company dedicated to the development of nitric oxide-donating drugs to meet unmet medical needs. NicOx is targeting the therapeutic areas of inflammatory and cardio-metabolic diseases. Resources are focused on two lead compounds, naproxcinod, in phase 3 development for the treatment of osteoarthritis, and NCX 4016, in phase 2 for type 2 diabetes. NicOx has strategic partnerships with some of the world’s leading pharmaceutical companies, including Pfizer Inc and Merck and Co., Inc. NicOx S.A. is headquartered in Sophia-Antipolis, France, and 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 of reference.
Source: NicOx S.A.
