Musculoskeletal Diseases

June 1, 2015

Zafgen issued results of a phase II study of beloranib for Prader-Willi syndrome (PWS). The proof-of-concept study had a two-week, single-blind, placebo lead-in period followed by a four-week, double-blind, randomized treatment period of beloranib 1.2mg, 1.8mg or placebo administered as twice-weekly subcutaneous injections. The trial enrolled 17 patients with a mean BMI of 31.4kg/m2 and mean BW of 71.8kg. Results showed beloranib appeared safe and well-tolerated, and led to dose-dependent body and total fat mass reductions despite a 50% increase in total daily calorie intake. Treatment with beloranib also reduced hyperphagia-related behaviors typical of patients with PWS, and improved biomarkers associated with cardiovascular disease risk and adipose tissue function. The effects of beloranib treatment on body mass and total fat mass in this trial were similar to those seen in non-PWS obese patients, indicating beloranib effects are evident in PWS as well. Based on these study results, Zafgen has moved forward with the program in PWS and currently is conducting a phase III trial in the U.S.

October 8, 2012

Sarepta Therapeutics released results from a phase IIb trial of eteplirsen for the treatment of Duchenne muscular dystrophy (DMD). This randomized, multi-arm, placebo-controlled study enrolled 12 males aged seven to 13 years old. Subjects received either eteplirsen 30mg/kg or 50mg/kg once weekly for 48 weeks, or for 24 weeks followed by another 24 weeks of placebo. The trial met its efficacy endpoint, increase in novel dystrophin, and achieved a significant clinical benefit on the primary clinical outcome, the six-minute walk test (6MWT) over the placebo/delayed treatment cohort. Data showed a statistically significant increase (p≤0.001) in dystrophin-positive fibers to 47.0% of normal. The placebo/delayed treatment cohort also showed a statistically significant increase in dystrophin-positive fibers to 38.3% of normal (p≤0.009). Patients who received 50mg/kg of eteplirsen demonstrated an increase of 21.0 meters in distance walked from baseline (mean=396.0 meters), while patients who received placebo/delayed-eteplirsen treatment showed a decline of 68.4 meters from baseline (mean=394.5 meters). The drug was well tolerated. There were no treatment-related adverse events.

December 10, 2007

Avicena released positive results from a phase II trial of AL-08 for the treatment of Amyotrophic Lateral Sclerosis (ALS). This randomized, double-blind, selection trial enrolled one hundred and twenty subjects who received AL-08 in combination with minocycline or AL-08 in combination with celecoxib. The primary objective was to determine treatment selection based on which drug combination appeared to slow deterioration in the ALS-Functional Score. Results showed subjects treated with AL-08/celcoxib showed a smaller mean functional decline versus AL-08/minocycline. At the end of the trial, the decline in ALS-Functional Score in both treatment arms was compared separately to the mean historical control group at a 0.05 significance level. The mean decline in ALS-Functional Score was 5.27 in the celecoxib/creatine arm, compared to 6.47 in the minocycline/creatine arm, and 5.82 in the historical control group. Based on the results, Avicena plans to move forward with phase III trials.

September 17, 2007

Santhera reported positive results from a clinical trial of SNT-MC17 for the treatment of Friedreich's Ataxia (FRDA). This 6-month, randomized, double-blind, placebo-controlled study was conducted by the US National Institutes of Health. The trial enrolled 48 subjects, aged 9 to 17 years, with genetically confirmed FRDA. The subjects received placebo or one of three doses of SNT-MC17. The primary endpoint was the change from baseline in urinary 8-hydroxy-2'-deoxyguanosine (8OH2'dG). Secondary endpoints included the change on the International Cooperative Ataxia Rating Scale (ICARS) and the Friedreich Ataxia Rating Scale (FARS). The endpoints were achieved, with dose dependent improvements observed in each. In addition, there was a change in neurological function from baseline of 10 to 17%. Phase III trials of SNT-MC17 are currently underway.

March 13, 2006

BioMS Medical has issued positive results of a phase II extension trial of MBP8298, for the treatment of multiple sclerosis (MS). Results from the extension study, designed to investigate the drug's ability to slow disease progression, indicated that in a subset of patients with progressive disease who expressed the HLA-DR2 or HLA-DR4 immune response genes, the drug significantly increased median progression-free survival to 78 months, compare to 18 months for placebo (p=0.004). Patients expressing these genes comprise roughly 75% of MS patients. This placebo-controlled follow-up treated 20 HLA-DR2 or HLA-DR4 patients, who received 500 mg MBP8298 or placebo every 6 months. These data were seen to support an ongoing phase II/III trial of the drug, currently enrolling up to 553 patients.

Corgentech issued positive results of a phase II trial of ALGRX 4975, for the treatment of elbow tendonitis pain. Trial data met their primary efficacy endpoint, with 64% of subjects receiving the drug (n=14/22) achieving clinical response (no or slight pain upon wrist dorsiflexion), compared to 30% (n=7/23) for placebo at week 4 (p=0.0256). Efficacy was maintained through week 8, and a trend for reduced pain score for weeks 2 through 12 was noted. Treatment was generally well tolerated at all time points through 24 weeks, and secondary endpoints were also positive. This randomized, double-blind, placebo-controlled study enrolled 45 patients at 2 sites, who received an injection of the drug or placebo, prior to treatment with a local anesthetic.

May 2, 2005

Genzyme has reported interim results of a pivotal trial of Myozyme (alglucosidase alfa), under investigation for the treatment of Pompe disease, a rare hereditary progressive muscle disease. Results from this ongoing study had not yet reached their primary endpoint, survival vs. historical baseline through 18 months, but improvement was seen in several secondary measures, including the finding that 89 percent of patients treated with Myozyme (n=16) were alive and not dependent on ventilator support at 12 months, compared with 17 percent of patients in the historical cohort. Furthermore, all patients treated with Myozyme showed a reversal in cardiomyopathy, 72 percent of patients treated with Myozyme demonstrated gains in motor development, and all patients demonstrated improvements in cognitive, language and personal/social skills from baseline. This open- label trial enrolled 18 patients with infant- onset Pompe disease, who began receiving the drug by 6 months of age. The company announced that primary efficacy results were expected during summer 2005, when subjects will have completed 52 months of therapy.

April 4, 2005

Aeolus Pharmaceuticals reported interim results from a phase I trial investigating AEOL 10150, a antioxidant neuroprotectant under development for the treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). Interim data demonstrated that was well tolerated compared to placebo. Results showed that plasma AUC values ranged from 354.2 ng*hr/mL in the 3 mg group to 4579.9 ng*hr/mL in the 30 mg group. Cmax ranged from 114.8 ng/mL to 733.4 ng/mL, and mean Tmax ranged from 0.5 to 1.3 hours in these same groups. The half-life of AEOL 10150 ranged from 2.61 to 5.25 hours. The most frequently reported adverse events were injection site reactions, dizziness and headache. No serious adverse events were reported. The multi-center, double-blind, randomized, placebo-controlled escalating single dose study is enrolling up to 5 subjects with ALS. The study is designed to evaluate the safety, tolerability and pharmacokinetics of the drug administered by subcutaneous injection. Single doses of up to six levels of AEOL 10150(3, 12, 30, 45, 60, and 75 mg) are being administered.

March 14, 2005

BioMarin has announced positive results from a phase III extension study of Aryplase (galsulfase, rhASB), their investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI), also called Maroteaux-Lamy Syndrome. Results from the 6-month extension indicated that the drug improved muscular endurance over the already-significant improvements seen at the end of the initial trial, during extension period (weeks 24-48). This included an improvement of 36 meters in distance walked in 12 minutes, an improvement in 2.9 stairs in total stairs climbed in 3 minutes, and maintained initial reduction in urinary glycosaminoglycan levels, at 48 weeks, versus the baseline levels obtained at the end of the initial study (24 weeks). This open-label extension study enrolled all 38 patients who had completed the initial 24 week trial; all patients received 1.0 mg/kg Aryplase via weekly infusion.

April 7, 2003

BioMarin reported positive results from a phase II trial investigating Aryplase (recombinant human arylsufatase B), an enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI). Results showed the drug was well tolerated and that subjects experienced improvement in endurance. Subjects achieved an average improvement of 64 meters (62%) in the 6-minute walk test and an average improvement of 155 meters (98%) in the 12-minute walk test. Subjects also exhibited functional improvements in joint pain and stiffness scores, which were reduced on average by 57% and 54% respectively. The open-label study enrolled 10 subjects with MPS VI and was conducted at two sites in the U.S. and one in Australia. The study evaluated clinical and biochemical measures of saftey and efficacy of Aryplase in subjects aged 6 to 22 for 22 weeks.

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