FDA Grants Orphan Drug Designation to Bertilimumab for Treatment of Bullous Pemphigoid

This morning, August 20, 2018, the US Food and Drug Administration (FDA) granted an orphan drug designation to Immune Pharmaceuticals, Inc.’s bertilimumab for the treatment of bullous pemphigoid, a rare autoimmune, chronic skin disorder.

“We are incredibly gratified that bertilimumab has received an orphan drug designation for the treatment of bullous pemphigoid from the FDA and believe this designation, coupled with the recent positive opinion from the EMA’s Committee for Orphan Medicinal Products represent a significant regulatory milestone or bertilimumab,” said Immune’s chief medical and operating officer, Tony Fiorino, MD, PhD, in a recent statement.

Previously, bertilimumab was evaluated in an open-label, single-arm, phase 2 trial in patients with moderate-to-extensive bullous pemphigoid at sites throughout the United States and Israel. The primary outcome measure for the trial included safety endpoints that assess the number of adverse events (AEs), injection site reactions after infusions, abnormal physical findings during examination, abnormal vital signs (blood pressure, heart rate, temperature), abnormal electrocardiogram (ECG), number of concomitant medications taken, abnormal normal laboratory values, and development of anti-bertilimumab antibodies as measured in the timeframe of 118 days, the average study duration.

Secondary outcome measures included a variety of efficacy measures related to clinical signs and symptoms and tapering of systemic corticosteroids. They included the following: change in BPDAI Activity Score (a validated measure of bullous pemphigoid disease activity consisting of four subscores: skin blistering [0 to 120], uricaria [0 to 120], mucosal blistering [0 to 120] and damage/pigmentation [0 to 12]); BPDAI responders (the proportion of participants who achieve a reduction in BPDAI Activity Score of at least 50%, 75%, and 90% at days 42, 56, 70, or 84); prednisone dose (the proportion of participants who have tapered to prednisone dose of ≤10 mg/day at days 42, 56, 70, or 84); change in BPDAI pruritus component (change in pruritus visual analog scale which is the sum of three 0 to 10 pruritus assessments measuring pruritus intensity over the prior day, week, and month at each scheduled measurement timepoint; change in Autoimmune Bullous Disease Quality of Life (a validated 17 item questionnaire (range 0 to 51) assessing quality of life in patients with autoimmune blistering diseases that is assessed at each scheduled measurement timepoint); and control of disease activity (defined as the time when at least 2 of the following occur: new lesions cease to form, established lesions begin to heal and/or pruritic symptoms start to abate).

Patients enrolled in the phase 2 trial were administered bertilimumab intravenously at a dose of 10 mg/kg on days 0, 12, and 28 and were followed for a total of 84 days. Participants were also administered a low dose of prednisone that was to be tapered rapidly, in accordance with the subject's clinical status.

Out of the 11 subjects enrolled in the trial, 9 were administered bertilimumab, which was well tolerated in all 9 participants as no drug-associated serious adverse events were reported. Additionally, preliminary analyses exhibited that the participants in this study had an 81% decline in the Bullous Pemphigoid Disease Area Index (BPDAI) Total Activity Score. Furthermore, participants displayed a marked improvement in their disease despite an initial prednisone dose of 0.33 mg/kg that was reduced by over 50% by day 84.

Looking forward, Dr. Fiorino added, “We are focused on putting all of the manufacturing and regulatory pieces in place to launch a pivotal phase 2/3 study of bertilimumab in bullous pemphigoid next year.”