• Addex Pharmaceuticals Ltd., of Geneva, said that ADX10061, an orthosteric dopamine D1 receptor antagonist, did not meet the primary efficacy endpoint in a Phase IIa trial in smoking cessation, failing to demonstrate a treatment effect compared to placebo. The study included 145 patients in the intent-to-treat population, with a primary endpoint defined as an increased number of patients with four weeks continuous smoking abstinence, starting from the beginning of week four of treatment. Results showed no separation of ADX10061-treated patients from placebo. The major secondary efficacy endpoints also failed to reach significance, and Addex said it will discontinue development of ADX10061 for smoking cessation. ADX10061 was in-licensed from Cambridge, UK-based CeNeS Pharmaceuticals plc in 2002. Addex might evaluate other opportunities for the compound in the future, but has no specific plans at this time and will focus, instead, on its internal portfolio of allosteric modulators, including ADX10059, which has shown efficacy in Phase IIa studies in gastroesophageal reflux diseases and migraine.

• Ardea Biosciences Inc., of Carlsbad, Calif., said the FDA cleared the company to start Phase I testing of RDEA119, a selective inhibitor of mitogen-activated ERK kinase (MEK), in advanced cancer patients. The trial will evaluate RDEA119 for safety, tolerability and pharmacokinetics and will examine biomarkers of therapeutic activity. That drug is the first to emerge from Ardea's MEK program, though the company aims to bring a second compound to the clinic in the fourth quarter.

• ChemGenex Pharmaceuticals Ltd., of Melbourne, Australia, said early data from its Phase II/III study of Ceflatonin (omacetaxine mepesuccinate) suggested the drug could benefit chronic myeloid leukemia patients with T315I point mutations. Data from four Gleevec (imatinib mesylate)-resistant chronic phase, T315I-positive CML patients showed hematologic response, disease stabilization and dramatic reductions in the levels of the T315I mutation. Ceflatonin was generally well tolerated, and no patients demonstrated unacceptable side effects. Those results were presented at the CML conference in Mandelieu, France.

• Critical Therapeutics Inc., of Lexington, Mass., started a Phase I trial to test an oral, single dose of the R-positive isomer of zileuton in healthy subjects. R-positive zileuton, combined in equal proportion with its mirror image isomer, S-negative zileuton, comprises racemic zileuton, the pharmaceutical ingredient in Zyflo tablets and ZYFLO CR extended-release tablets. The trial is expected to enroll 12 subjects to be randomized to one of two groups and will investigate the product's pharmacokinetic and pharmacodynamic profile when dosed alone.

• MacuSight Inc., of Union City, Calif., reported positive data from a Phase I study of its lead candidate, sirolimus (rapamycin) in patients with chronic, clinically significant diabetic macular edema showing that the drug was safe and well tolerated in all doses tested with two different routes of administration (intravitreal or subconjunctival injection). Data from the 50-patient trial also showed improvements in visual acuity and foveal thickness reductions for up to 180 days following a single administration of sirolimus. At 45 and 90 days following treatment, patients receiving the two lowest doses of sirolimus by subconjunctival injection demonstrated mean improvements in visual acuity of 8.5 and 7.4 letters over baseline, respectively, using a standard eye chart. Findings were presented at the Retina Society meeting in Boston, and MacuSight intends to present final data later this year. The company also has completed enrollment in a second Phase I study to test sirolimus in patients with exudative age-related macular degeneration, with results from that trial expected in the first half of 2008.

• Nastech Pharmaceutical Co. Inc., of Bothell, Wash., started a Phase II trial of PYY3-36 Nasal Spray in obese patients. The six-month study is expected to involve about 500 patients randomized to receive either one of three doses of the nasal spray or placebo and the oral weight loss drug sibutramine (Meridia, Abbott). The primary endpoint is weight loss. PYY3-36 is a nasal formulation of the peptide YY hormone that is believed to function as a physiologic inhibitor of food intake.

• Oncolytics Biotech Inc., of Calgary, Alberta, reported interim results from a UK Phase Ia/Ib combination Reolysin and radiation trial in patients with advanced or metastatic cancers, which showed that, of 11 patients in the Phase Ia portion who received two intratumoral treatments of Reolysin, given at four different dosages, with a constant localized radiation dose of 20 Gy given in five fractions, three experienced significant partial responses. One month following treatment, a patient with esophageal cancer experienced a 28.5 percent reduction in the target tumor, with stable disease noted in four, nontreated tumors. A patient with squamous skin cancer experienced a 50 percent reduction in the target tumor at one, two and three months post-treatment, and a squamous-cell scalp patient showed stable disease in the target tumor for two months and then showed partial response at three months. Data were presented at the Cancer Research Institute conference in Birmingham, UK.

• Orexo AB, of Stockholm, Sweden, completed a pharmacological profile for Sublinox (OX22) showing that the drug acts 30 percent faster than Ambien (Sanofi-Aventis Group) as a sleep aid for patients suffering from sleep disturbances. Results also showed that patients remain asleep throughout the night. The completed effects study, combined with additional clinical documentation produced by Orexo, will serve as the basis for the registration application that the company anticipates submitting to the FDA later this year. Sublinox contains zolpidem and is based on Orexo's sublingual technology for absorption across the oral mucosa.

• Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., and development partner Bayer HealthCare AG, of Leverkusen, Germany, said a full analysis of the primary 12-week endpoint of the Phase II study showed that VEGF Trap-Eye met the primary endpoint of statistically significant reduction in retinal thickness after 12 weeks of treatment in patients with wet age-related macular degeneration (AMD) compared with baseline. The trial enrolled 157 patients who were randomized to five groups and treated with VEGF Trap-Eye in one eye, with two groups receiving monthly doses of 0.5 mg or 2 mg and three groups receiving quarterly doses of 0.5 mg, 2 mg or 4 mg. All dose groups showed a reduction in retinal thickness, and preliminary 16-week data showed that retinal thickness for all five groups combined continued to improve, with a mean decrease of 159 microns vs. baseline. The mean change from baseline in visual acuity, a secondary endpoint, also demonstrated statistically significant improvement, and preliminary analyses at 16 weeks showed that the VEGF Trap-Eye, dosed monthly, achieved a mean gain in visual acuity of 9.3 to 10 letters (for the 0.5 mg and 2 mg dose groups, respectively.) Regeneron and Bayer started a Phase III development for VEGF Trap-Eye in August to compare the product to Lucentis (ranibizumab, Genentech Inc.), the leading wet AMD drug. (See BioWorld Today, Aug. 6, 2007.)

• Transgene SA, of Strasbourg, France, enrolled the first patients in a Canadian Phase I trial of TG4040 (MVA-HCV), a therapeutic vaccine candidate, in patients with chronic hepatitis C virus infection who have relapsed after standard treatment of ribavirin and pegylated interferon alpha. The 24-patient study, which is sponsored by the University of Montreal and supported by the Canadian Network for Vaccines and Immunotherapies, is designed to test one subcutaneous injection of TG4040 per week, with dosing escalating in several cohorts, over a three-week period together with a boost injection at month six. The primary endpoint is safety, and the secondary endpoints are immune response to the vaccination and effect on viral load. Data are expected by the end of 2008.

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