Dermatology

Senetek issued positive results from a phase I trial of Pyratine-6 for the treatment of acne rosacea. This study enrolled 24 subjects with mild-to-moderate acne rosacea. They were evaluated at baseline, four, eight and twelve weeks for physician assessments of inflammatory lesion count, severity of erythema and telangiectasia, transepidermal water loss measurements and overall clinical improvement. Pyratine-6 produced a progressive decrease in the symptoms associated with rosacea including redness and acne lesions. All subject self-assessments showed good tolerability and cosmetic acceptability. After 12 weeks there was overall clinical improvement in 80% of subjects, including reduction of erythema and papules. Transepidermal water loss measurements showed a 22% decrease in water loss, which supports an improvement in skin barrier function. Based on these results, Senetek extended this study to 48 weeks.

Oncology

Nektar reported positive results from a phase I trial of NKTR-118 for the treatment of opiod-induced bowel dysfunction. This multi-dose, double-blind, randomized, placebo-controlled study enrolled 32 healthy subjects not receiving opioid therapy. The subjects received NKTR-118 (in escalating doses up to 250 mg) or placebo twice daily for seven days, with a single dose on the eighth day. NKTR-118 was shown to be safe and generally well-tolerated at doses up to 250 mg twice daily, with no serious or severe adverse events. The pharmacokinetics of NKTR-118 were dose-proportional and the observed terminal half-life of the drug was approximately eleven hours, independent of dose. At all dose levels, NKTR-118 was rapidly absorbed after oral administration, as evidenced by a steep increase of plasma NKTR-118 concentration. Phase II trials of NKTR-118 are currently underway.

Ophthalmology

Novartis released positive results from a phase III trial of Menveo, a vaccine for the prevention of meningitis. This head to head study enrolled 2,100 subjects, aged eleven to eighteen years, who received a single vaccination with either Menveo or Menactra, an FDA approved vaccine. Data showed that the subjects who were immunized with Menveo generated higher levels of antibodies against four meningococcal serogroups: A, C, W-135 and Y. One month after vaccination geometric mean titers for Menveo versus Menactra were: serogroup A, 29 versus 18; serogroup C, 59 versus 47; serogroup W-135, 87 versus 44 and serogroup Y, 51 versus 18. The percentage of subjects who achieved a protective immune response, determined by a human serum bactericidal antibody titer (hSBA) > 1:8, with Menveo compared to Menactra was: serogroup A, 75% versus 67%; serogroup C, 84% versus 84%; serogroup W-135, 96% versus 88%; and serogroup Y, 88% versus 69%. In addition, among adolescents with low levels of immunity at the time of vaccination, 81% who received Menveo generated a protective immune response against serogroup Y versus 54% with Menactra. Based on positive phase results Novartis plans to submit a BLA to the FDA by the end of 2008.

Neurology

Genzyme reported positive preliminary results from an ongoing phase II trial of Genz-112638 for the treatment of Gaucher Disease. This open label study enrolled 26 adult subjects with Type 1 Gaucher disease at medical centers in North America, South America, Europe and Israel. The primary endpoints were changes in hemoglobin, platelet levels and spleen volume. At six months spleen volumes had decreased from baseline by a mean of 27% of the 21 subjects for whom data were available; at one year spleen volumes had decreased by 40% among 11 evaluable subjects. At six months hemoglobin levels had increased from baseline by a mean of 0.9 grams per deciliter of blood among 17 evaluable subjects; at one year hemoglobin levels had increased by 1.3 grams per deciliter among 13 evaluable subjects. Platelet counts increased from baseline by a mean of 18% among 17 subjects treated for six months and by 34% among 13 subjects with available data at one year. Chitotriosidase levels decreased from baseline by a mean of 30% at six months among 20 evaluable and by 50% among 12 evaluable subjects treated for one year. All reported adverse events were mild and transient in nature. Genzyme is currently developing phase III protocols and expects to commence these studies in 2009.

QRxPharma issued positive results from a phase III trial of Q8003IR for the treatment of moderate to severe pain. This double-blind, placebo-controlled study enrolled 256 subjects with moderate to severe pain following bunionectomy, in the United States. The subjects received one of four different dosage regimens of Q8003IR or placebo over a 48 hour dosing period. Per treatment group, median doses received every four hours ranged from 3mg/2 mg to 9mg/6 mg of Q80031R. The primary endpoint was the change in pain intensity scores over the 48 hour dosing period (SPID48) in subjects receiving Q8003IR versus placebo. A strong dose-response effect in reducing pain intensity scores (SPID48) and other measures of analgesic effect were observed (p<0.001). In addition, among all Q8003IR treatment arms approximately 50% of the subjects reported good to excellent global improvement compared to 13% for placebo. Q8003IR was generally well tolerated. Based on positive phase III results QRxPharma plans to submit an NDA to the FDA in 2009.

Schwarz Pharma released positive results from a phase III trial of lacosamide for the treatment of diabetic neuropathic pain. This placebo-controlled, withdrawal study was a sub-trial of an open- label, follow-on to a phase III, double-blind trial. Subjects had been followed for a mean of twenty months before entering the sub-trial. Prior to any lacosamide treatment, subjects had an average daily pain score of 6.5. After more than a year of open-label treatment, the mean pain score was 2.5, the baseline score of the withdrawal sub-trial. A total of 106 subjects treated with lacosamide (100-400 mg/day) participated in the withdrawal study. In a blinded fashion, lacosamide was withdrawn (less than or equal to twenty-eight days) and reintroduced. The primary endpoint was the change in average daily pain score from baseline to the last seven days of each period, using the 11-point Likert pain scale. The difference in average daily pain scores was statistically significant in favor of lacosamide over placebo (p= 0.007). Average daily pain scores increased during placebo treatment and improved to values similar to sub-trial baseline (2.5 on the pain scale) when lacosamide was reintroduced. A key secondary endpoint, worsening of pain when lacosamide was withdrawn, was also reached. The intra-individual change in average daily pain score from open-label lacosamide treatment at baseline to the end of the placebo period was statistically significant (p<0.001). More subjects receiving placebo (39%) versus lacosamide (29%) experienced sustained worsening of pain during the withdrawal periods. Treatment was safe and well tolerated. An MAA and NDA are currently under review by the EMEA and FDA, respectively.

Ophthalmology

Pfizer and NicOx reported mixed results from a phase II trial of PF-03187207 for the treatment of primary open-angle glaucoma or ocular hypertension. This US based, randomized, double masked study enrolled 215 subjects with one of these two conditions in one or both eyes. The subjects received twenty-eight days of treatment with either morning or evening doses of Xalatan 0.005% or five different doses of PF-03187207, some of which were tested with both morning or evening dosing arms. Intraocular pressure (IOP) was measured at 8am, 10am, 1pm and 4pm, at baseline and on days 7, 14, 21 and 28. The primary endpoint compared the two treatments in terms of the change in mean IOP from baseline at day 28. On this primary endpoint, evening administration of the highest dose of PF-03187207 showed a 12% (approximately 1 mmHg) greater reduction in diurnal IOP than evening administration of Xalatan, however this difference did not reach statistical significance. Secondary endpoints were reached with statistical significance. These included IOP lowering from baseline at 4 pm as an average across all study visits; evening administration of PF-03187207 was statistically significantly better than evening dosing of Xalatan by 22%, approximately 1.4 mmHg (p<0.05). Additional secondary endpoints were the reductions in diurnal IOP from baseline on days 7, 14 and 21, as well as the reductions from baseline at 8 am, 10 am, 1 pm and 4 pm, as an average across all study visits. Morning administration of the highest PF-03187207 dose demonstrated a statistically significant advantage compared to morning dosing of Xalatan on a number of these secondary endpoints, with the difference in IOP lowering ranging from 25% to 35%, approximately 1 mmHg to 2 mmHg (p<0.05). Based on the results Pfizer has decided not to launch a global phase III program. A phase II trial is currently underway in Japan; pending positive results Pfizer and NicOx may pursue potential registration in Asia.