Regulatory Decision Summary for OCTAGAM

Marketing authorization was based on the results of one double-blind, placebo-controlled trial. Patients with dermatomyositis were randomized to receive either 2.0 g/kg OCTAGAM or placebo (saline) every 4 weeks during the 16-week First Period. At Week 16, patients in both groups entered the subsequent 6-month open-label Extension Period to receive 2.0 g/kg OCTAGAM every 4 weeks.

A total of 95 adult patients were included in the trial: 47 to the OCTAGAM group and 48 to placebo group. The median (range) of age was 55 (22-77) years for the OCTAGAM group and 52 (22-79) years for the placebo group. The median (range) time since diagnosis of dermatomyositis was 2.35 (0.1-48.7) years for the OCTAGAM group and 2.86 (0.1-18.4) years for the placebo group.

The efficacy was assessed by the Total Improvement Score, which was derived from the evaluation of six measurements of myositis disease activity, including Physician’s Global Disease Activity, Patient’s Global Disease Activity, Manual Muscle Testing-8, Health Assessment Questionnaire, Extra-muscular Activity and Enzymes (alanine aminotransferase, aspartate aminotransferase, aldolase, creatine kinase, and lactic dehydrogenase). The Total Improvement Score was a scale from 0 to 100 points. In addition, Cutaneous Dermatomyositis Disease Area and Severity Index was also assessed to measure the damage in the skin.

The primary endpoint was to compare the proportions of the responders at Week 16 between two groups. A responder was defined as a patient with an improvement of ≥20 points on the Total Improvement Score compared to the baseline. The proportions of responders at Week 16 were significantly higher in the OCTAGAM group than in the placebo group: 78.7% vs. 43.8%; p = 0.0008.

The secondary endpoints, the proportions of patients with an improvement of ≥40 and ≥60 points on the Total Improvement Score at Week 16 compared to baseline, also showed the greater improvements on the Total Improvement Score in the OCTAGAM group (68.1% and 32.0%) versus the placebo group (22.9% and 8.3%).

In addition, an improvement in the Cutaneous Dermatomyositis Disease Area and Severity Index total activity score was observed in the OCTAGAM group: the mean decrease of 9.4 (±10.5) points from baseline to Week 16 in the OCTAGAM group versus 1.2 (±7.0) point in the placebo group.

Furthermore, the OCTAGAM group maintained their improvement on total improvement score at Week 40. The proportions of responders at Week 40 was 71.1% in the OCTAGAM group. In the placebo group, 69.9% patients who switched from placebo to OCTAGAM at Week 16 were classified as responders at Week 40.

OCTAGAM at a dose level of 2.0 g/kg (20 mL/kg) every 4 weeks and at an infusion rate of 0.04 mL/kg/min was generally well tolerated in the adult patients with dermatomyositis. The most commonly reported treatment-emergent adverse events were headache, pyrexia, and nausea in the patients who received OCTAGAM; and was condition aggravated in the patients who received placebo. Six patients (6.3%) who received OCTAGAM reported 8 thromboembolic events: pulmonary embolism, deep vein thrombosis, cerebrovascular accident, and cerebral infarction. No patients who received placebo reported any thromboembolic events.

Thromboembolic events is a known risk in patients with dermatomyositis receiving OCTAGAM. Risk mitigation measures have been included in the Product Monograph: a warning of dermatomyositis as a risk factor for thromboembolic events and a warning regarding the maximum infusion rate in dermatomyositis patients. 

Based on the submitted clinical data, the benefits of OCTAGAM outweigh the risks in patients with dermatomyositis at a dose level of 2.0 g/kg (20 mL/kg) every 4 weeks and at an infusion rate of 0.04 mL/kg/min.