Trial Results

Lilly’s Galcanezumab Meets Primary Endpoint in Phase III Study

May 21, 2018

Eli Lilly and Company announced that galcanezumab met its primary endpoint in a Phase III study of patients with episodic cluster headache, demonstrating statistically significant differences in the reduction of weekly cluster headache attacks compared to placebo across weeks one to three of the two-month, double-blind treatment period. The episodic cluster headache study was a randomized, double-blind, placebo-controlled global trial evaluating the safety and efficacy of galcanezumab (300 mg once-monthly) administered subcutaneously compared with placebo in 106 patients with episodic cluster headache. Patients who participated in this trial had an average of 17.5 cluster headache attacks per week at baseline. The primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency across weeks one to three with galcanezumab compared with placebo. In this study, eight percent of patients treated with galcanezumab discontinued treatment during the study compared to 21 percent of patients treated with placebo. Discontinuations due to lack of efficacy occurred in two percent of patients treated with galcanezumab, compared to 14 percent of patients treated with placebo.

Concentric Analgesics Announces Positive Topline Results Post-Surgical Pain Trial
Concentric Analgesics announced topline results from its Phase Ib clinical trial for CA-008 in post-surgical pain. The primary objective of the clinical study was to demonstrate the safety and pharmacokinetics of CA-008, with secondary endpoints including efficacy. The study showed that CA-008, a novel, non-opioid therapeutic, was well tolerated at all dose levels compared to the control group following surgery in bunionectomy patients. The highest dose cohort of CA-008 showed statistically significant and clinically meaningful (greater than 50 percent) reductions in area under the curve (AUC) for pain intensity compared to the control group lasting up to 168 hours. The randomized, double-blind, placebo-controlled, dose-escalation study enrolled 40 patients undergoing bunionectomy with standard of care Mayo block (bupivacaine HCl 0.5 percent, up to 30 ml) and evaluated the safety of CA-008 compared to a saline control. The study was comprised of five cohorts of eight patients each, with six patients receiving CA-008 at ascending doses and two patients receiving control. Across the five cohorts, 30 patients received CA-008 across a nearly 10-fold dose range. The primary endpoints of this Phase Ib study were safety and pharmacokinetics, with various secondary endpoints including the effect on pain intensity out to two weeks post-surgery.

Regeneron Pharmaceuticals Announces Positive Results for Phase III
Regeneron Pharmaceuticals and Sanofi announced that a pivotal Phase III trial evaluating DUPIXENT (dupilumab) to treat moderate-to-severe atopic dermatitis met its primary and key secondary endpoints. In the trial, treatment with DUPIXENT as monotherapy significantly improved measures of overall disease severity, skin clearing, itching and certain health-related quality of life measures. The pivotal, Phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of DUPIXENT monotherapy in adolescent patients with moderate-to-severe atopic dermatitis. The trial enrolled 251 patients who were 12 years to 17 years of age with moderate-to-severe atopic dermatitis whose disease could not be adequately controlled with topical medications or for whom topical treatment was medically inadvisable. In total, 92 percent of these patients suffered from at least one concurrent allergic condition such as allergic rhinitis, asthma or food allergy. The primary endpoints were the proportion of patients achieving Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and 75 percent improvement in Eczema Area and Severity Index (EASI-75, co-primary endpoint outside of the U.S.). Results showed 24 percent of patients who received weight-based dosing of DUPIXENT every two weeks (200 mg or 300 mg) and percent of patients who received a fixed dose of DUPIXENT every four weeks (300 mg) achieved the primary endpoint – clear or almost clear skin (IGA; score of 0 or 1) – compared with 2 percent with placebo (p less than 0.0001, and p=0.0007, respectively). Patients treated with DUPIXENT had significant improvement in disease severity at 16 weeks.

BioMarin Announces First Patient Dosed in Phase I/II Study
BioMarin Pharmaceutical announced that it has dosed the first patient in a Phase I/II study (BMN 270-203) evaluating its investigational gene therapy, valoctocogene roxaparvovec, in severe hemophilia A patients with pre-existing AAV5 antibodies. The study is an open-label, single-arm, titer-escalation trial evaluating the safety and efficacy of valoctocogene roxaparvovec in AAV5+ hemophilia A patients. Patients with pre-existing AAV5 antibodies will be sequentially enrolled into two titer cohorts that will encompass the range of observed AAV5 antibody titer levels generally observed in the hemophilia population and be treated with the 6e13 vg/kg dose. The primary endpoint will evaluate safety of valoctocogene roxaparvovec in this population. Secondary endpoints include assessment of FVIII activity level, frequency of required FVIII replacement therapy, and the number of bleeding episodes requiring treatment after therapy. BioMarin is also evaluating the 6e13 vg/kg dose in GENEr8-1 and a second dose of 4e13 vg/kg in GENEr8-2.