• BioMarin Pharmaceutical Inc., of Novato, Calif., said treatment was initiated in a Phase IIa trial of 6R-BH4 (sapropterin dihydrochloride) for the treatment of sickle cell disease. The multicenter, open-label study is designed to assess the safety and biologic activity of escalating doses in 40 SCD patients not receiving hydroxyurea therapy. In addition to safety, the trial will assess changes in physiological and biochemical markers of endothelial function, which underlie some key aspects of SCD, BioMarin said. 6R-BH4, commonly known as BH4 or tetrahydrobiopterin, is a naturally occurring enzyme cofactor required for numerous biochemical and physiologic processes, including the synthesis of nitric oxide. Trial data are expected to be available in the first half of 2008.

• CollaGenex Pharmaceuticals Inc., of Newtown, Pa., has suspended further enrollment in the 40 mg cohort in a Phase II trial of incyclinide for the treatment of acne. The move followed news that one patient experienced apparent significant photo-toxicity. After completing its investigation of the event, CollaGenex will meet with the FDA to discuss the development program for incyclinide. The company said since it saw no adverse events at lower doses, it is continuing the Phase II dose-finding trial of incyclinide for the treatment of rosacea. CollaGenex's stock (NASDAQ:CGPI) fell $2.60 Wednesday, or 18.1 percent, to close at $11.42.

• CuraGen Corp., of Branford, Conn., and TopoTarget A/S, of Copenhagen, Denmark, started a Phase I/II open-label, multicenter clinical trial evaluating the efficacy and safety of intravenous belinostat (PXD101), an HDAC inhibitor, in combination with doxorubicin for the treatment of soft tissue sarcomas. During the initial dose escalation part of the trial, up to 24 patients with solid tumors for whom no standard therapy exists will be enrolled in order to define the maximal tolerated dose of belinostat in combination with doxorubicin. The trial then will advance into Phase II and enroll an additional 20 to 40 STS patients who have not received chemotherapy. Patients will get standard doxorubicin chemo every three weeks, to which belinostat will be added in a five-day intravenous regimen. Patients demonstrating complete or partial response will continue to receive treatment with the combination for up to eight cycles or until disease progression.

• Generex Biotechnology Corp., of Worcester, Mass., said the first patients have been treated in a Phase II trial of the immunotherapeutic vaccine AE37, which is being developed by its wholly owned Antigen Express subsidiary. The trial is being conducted with the United States Military Cancer Institute's Clinical Trials Group. The randomized trial will compare breast cancer patients treated with AE37 plus the adjuvant GM-CSF vs. GM-CSF alone. The goal is to demonstrate at least a 50 percent reduction in the rate of relapse in AE37-treated patients. The second-generation peptide vaccine was designed using a fragment of the HER-2/neu oncoprotein.

• Isotechnika Inc., of Edmonton, Alberta, said partner Lux Biosciences Inc., of Jersey City, N.J., received a "no objection letter" from Health Canada to investigate LX211 (ISA247) in Phase II/III trials for the treatment of uveitis. Lux began a pivotal clinical trial program of the next-generation calcineurin inhibitor earlier this year in the U.S. The pivotal trial program, which consists of three controlled, double-masked studies, is investigating the use of ISA247 in different forms of active uveitis in addition to maintenance of quiescent disease. (See BioWorld Today, Feb. 21, 2007.)

• Merck Serono SA, of Geneva, said Phase III data on safinamide for Parkinson's disease showed that the addition of safinamide to a stable dose of a single dopamine agonist in patients with early stage Parkinson's disease resulted in a statistically significant improvement in motor symptoms, as measured by the Unified Parkinson's Disease Rating Scale1 (UPDRS) Part III Motor Score, the primary endpoint. After 24 weeks of treatment with safinamide at the dose of 50 mg to 100 mg once daily, the UPDRS Part III Motor Score was significantly improved over the effect of dopamine agonist monotherapy. Safinamide is an alpha-aminoamide derivative which is orally administered. Data were disclosed at the American Academy of Neurology meeting in Boston.

• Mesoblast Ltd., of Melbourne, Australia, said the FDA cleared the investigational new drug application of its U.S.-based sister company, Angioblast Systems Inc. It plans a Phase II trial of its allogeneic adult stem cells for patients with heart attacks. The trial based at the Texas Heart Institute will follow a similar protocol to the one used by the same investigators in preclinical studies. Those showed that implantation of stem cells by catheter into damaged heart muscle resulted in significant improvement in heart function and reduction in congestive heart failure.

• Nabi Biopharmaceuticals, of Boca Raton, Fla., said its NicVAX (Nicotine Conjugate Vaccine) met its primary endpoint - abstinence from nicotine between weeks 19-26 - in an ongoing Phase IIb proof-of-concept study. Data from the drug-treated population were divided into those who quit and those who continued to smoke and then analyzed for antibody levels throughout the trial. In an analysis of completers, patients who showed continuous abstinence between weeks 19-26 had significantly higher antibody levels than those who did not quit (p=0.03 and p=0.02 at the beginning and end of the eight-week assessment period, respectively). In an analysis of the intent-to-treat population, patients who quit smoking had a median total antibody level that was significantly greater than patients who continued smoking (p=0.002). The trial is continuing after all patients received a booster at six months. The study will assess a series of secondary endpoints at 12 months, including abstinence rate, total cigarette consumption, antibody concentration, safety and the degree of nicotine dependency.

• Neurogen Corp., of Branford, Conn., finished a single ascending dose, first-in-human study with NGD-4715, its leading drug candidate for the treatment of obesity. NGD-4715 works as a small molecule antagonist at the melanin concentrating hormone receptor-1. The compound was safe and well tolerated at all doses studied in this clinical trial, which enrolled 71 male and female subjects. NGD-4715 was studied across a broad range of doses, and blood levels of the compound exhibited a consistent dose dependent increase.

• Pozen Inc., of Chapel Hill, N.C., and GlaxoSmithKline plc, of London, reported new data showing that significantly more patients using the investigational migraine drug Trexima early in migraine attacks were pain-free at two hours and experienced relief from both traditional and nontraditional migraine symptoms, compared to patients receiving placebo. In those studies, more than 1,100 patients treated more than 3,300 migraine attacks, and endpoints included post-treatment incidence of traditional symptoms, defined as nausea, vomiting, photophobia and phonophobia, as well as nontraditional symptoms, such as sinus pain/pressure and neck pain/discomfort. Data were presented at the American Academy of Neurology meeting in Boston. Trexima is the proposed brand name for a single tablet containing sumatriptan 85 mg formulated with RT Technology and naproxen sodium 500 mg, and the product is under review at the FDA for treating acute migraines in adults.

• Sequella Inc., of Rockville, Md., said results from a Phase Ia trial found that SQ109, an oral diamine antibiotic for tuberculosis and other infectious diseases, was safe and well tolerated up to 300 mg, the highest dose tested, with no serious adverse effects reported at any dose level. The trial involved 62 healthy adult male and female patients. Data showed that oral administration of SQ109 produced measurable and dose-related plasma levels, with no drug-related changes in electrocardiograms, hematology or serum chemistry values. Sequella plans to conduct an additional Phase Ib study to demonstrate safety of daily administration of SQ109 alone and then in combination with other TB drugs in patients with pulmonary TB. Additional studies are expected to begin this quarter.

• Spectrum Pharmaceuticals Inc., of Irvine, Calif., initiated its pivotal Phase III trials for EOquin, its drug candidate for non-invasive bladder cancer. Those trials, which are being conducted under the special protocol assessment agreed upon in March, each will involve 562 patients with Ta G1 G2 non-invasive bladder cancer to be randomized in a 1-to-1 ration to EOquin or placebo. The primary endpoint is defined as the difference in the rate of tumor recurrence between the two treatment groups by year two. (See BioWorld Today, March 14, 2007.)

• Theratechnologies Inc., of Montreal, said the last patient has completed 52 weeks of treatment in its first Phase III study testing TH9507, a stabilized analogue of the growth hormone-releasing factor, in HIV-associated lipodystrophy. The firm expects to present top-line, 52-week results later this year. The study is examining the safety and efficacy of a daily administration of 2 mg of TH9507 for a period of 26 weeks and long-term safety over a period of 52 weeks. A second, confirmatory Phase III study got under way in January 2007.

• Y's Therapeutics Inc., of Burlingame, Calif., and Tokyo, initiated a Phase II trial of its lead compound, YSPSL, for prevention of ischemic reperfusion injury in liver transplant patients. The randomized, double-blind, placebo-controlled study is designed to enroll 12 patients undergoing cadaveric orthotopic liver transplantation. YSPSL is a recombinant molecule resulting from the fusion of P-selectin glycoprotein ligand (PSGL) and human IgG1.