Metabolic Disorders

February 25, 2013

Clasado published results from a phase I trial of Bimuno for metabolic syndrome in The Journal of Nutrition. This 28-week, double-blind, randomized, placebo-controlled, crossover study enrolled 45 overweight adults (body mass index > 25kg/m2) with at least three risk factors for metabolic syndrome. For the first 12 weeks, subjects received either 5.5g Bimuno-GOS or placebo. After a four-week washout period, subjects crossed over and received the other drug for another 12 weeks. Data demonstrated that Bimuno-GOS positively affected the gut microbiota by increasing the number of positive bifidobacteria, while reducing more negative bacteria. Positive effects were seen as early as six weeks. There was also a positive effect on immune responses by increasing faecal sIgA (marker of mucosal immunity), and decreasing calprotectin and CRP (markers of inflammation). Additionally, insulin, total cholesterol, triglycerides and TC/HDL ratio (markers of metabolic syndrome) were reduced. The drug was well tolerated.

August 9, 2010

BioMarin released positive preliminary results from a phase II trial of PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase) for the treatment of phenylketonuria. This open-label, multi-center study enrolled 23 adults who were placed in a series of dose-escalating cohorts starting from 0.001 mg/kg. The primary endpoint was to evaluate the effect of PEG-PAL on blood Phe concentrations. Seven subjects received at least 1 mg/kg/week for at least four weeks in several different dosing frequencies (up to three times per week). Of these, six had Phe levels below 600 umol/L for at least three weeks and up to three months. Their baseline Phe levels were reduced from a median of 1,293 umol/L to a median of 527 umol/L, representing an approximate 60% reduction in blood Phe. Two subjects had blood Phe levels documented below 5 umol/L. Injection site reaction was the most common treatment emergent adverse event.

July 19, 2010

Clinuvel reported positive results from a phase III trial of afamelanotide for the treatment of erythropoietic protoporphyria (EPP). This multicenter, randomized, double-blind, placebo-controlled trial, CUV017, treated 91 subjects over the course of 12 months. The subjects received a 16 mg subcutaneous resorbable implant formulation of afamelanotide or placebo once every two months for a total of six implants. The primary endpoints were the mean number of phototoxic reactions and the mean severity score for phototoxic reactions for active compared with placebo implants. The frequency of specific pain severity (severe, moderate, mild and none) was significantly reduced in the afamelanotide arm versus placebo (p≡0.0023). The average pain severity was also significantly reduced in the afamelanotide arm compared to placebo (p≡0.0017). An additional evaluation of the pain scores in patients willing to modify behavior by continuous exposure to daily sunlight showed a positive trend toward a reduction in average pain score following active drug treatment (p≡0.1654). The afamelanotide implant was well tolerated.

February 22, 2010

Protalix reported positive results from a phase III trial of taliglucerase alfa for the treatment of Gaucher disease. This 9-month, randomized, double-blind, parallel group, dose-ranging study enrolled 31 treatment naive subjects across several international sites. The subjects received either 60 units/kg or 30 units/kg of taliglucerase alfa administered intravenously once every two weeks. The primary endpoint, a 20% mean reduction in spleen volume after nine months compared with baseline values, was reached for both arms. The mean reduction in spleen volume was 38% for the 60 U/kg group and 26.9% for the 30 U/kg group (p<0.0001). These reductions were observed after six months of treatment. The secondary endpoints were also reached statistical significance with both doses. In the 60 U/kg dose arm there was a mean increase in hemoglobin of 2.2 g/dL or 22.2% (p<0.0001), a mean decrease in liver volume of 11.1% (p<0.0001) and a mean elevation in platelet count of 41,494 ml or 72.1% (p≡0.0031). In the 30 U/kg dose arm there was a mean increase in hemoglobin level of 1.6 g/dL or 14.8% (p&rquiv;0.0010) and a mean decrease in liver volume of 10.48% (p≡0.0041); a nominal elevation in platelet count was also seen (11,427 ml or 13.7%; p≡.0460). Taliglucerase alfa was well tolerated and no serious or severe adverse events were reported.

August 10, 2009

Shire reported positive preliminary results from a phase III trial of velaglucerase alfa for the treatment of Gaucher disease. This multicenter, randomized, double-blind, parallel-group, safety, efficacy and pharmacokinetic study enrolled 25 treatment naive subjects with type I Gaucher disease. The subjects received bi-monthly intravenous dosing of velaglucerase alfa at 45 and 60 U/kg, for 12 months. The primary endpoint, the increase in hemoglobin concentration from baseline, was reached with statistical significance in the 60 U/kg dose arm compared with baseline (p<0.0001). Statistically significant improvements compared with baselines were also observed in platelet and spleen sizes. While the primary endpoint was not reached with statistical significance in the 40 U/kg dose arm, statistically significant improvements in hemoglobin, platelet count, and spleen volume were demonstrated. Velaglucerase alfa was generally well tolerated with no drug-related serious adverse events.

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