The U.S. Food and Drug Administration (FDA) will review Shire’s application requesting that Cinryze (C1 esterase inhibitor [human]) be approved for the prevention of hereditary angioedema attacks in children 6 years and older.
The supplemental biologics license application (sBLA) received priority review, meaning the process will be shortened from the standard 12 months to eight months. A decision is expected by June 20.
Cinryze was approved by the FDA in October 2008, for routine prophylaxis (prevention) against attacks in teens and adults with hereditary angioedema (HAE), a rare disease that affects about one in 10,000 to 50,000 people worldwide.
HAE patients are prone to swelling due to a deficiency in C1-esterase inhibitor (C1-INH). The active substance in Cinryze is C1-INH, which raises plasma levels.
The treatment is designed to address the underlying cause of the rare disease by replacing the deficient protein and by regulating the production of bradykinin released during an attack.
Cinryze was the first C1-INH proven in clinical studies to help prevent swelling attacks in people with HAE. If the expanded indication is approved, Cinryze will be the first C1-INH therapy indicated to help prevent HAE attacks from childhood into adulthood.
“Adults and adolescents living with HAE have used Cinryze to help reduce the frequency and severity of attacks for nearly a decade,” Jennifer Schranz, global development lead for HAE at Shire, said in a press release. “Shire committed to studying the safety and efficacy of our HAE therapies in children aged 2 years and older because we understand the importance of this work to families in the HAE community. We look forward to working closely with the FDA in the coming months on this important review.”
The application is supported by data from two Phase 3 open-label studies, CHANGE 2 (NCT00438815) and CHANGE 3 (NCT00462709), and from two pediatric clinical trials, Phase 2 0624-203 (NCT01095510) and Phase 3 0624-301 (NCT02052141). Shire was the first to complete pediatric studies for the prophylactic treatment of HAE.
In a prior 24-week study of 22 people with HAE, patients were divided into two groups. One group received Cinryze for the first 12 weeks and switched to placebo for the next 12 weeks; the other group received placebo for the first 12 weeks and switched to Cinryze for the next 12 weeks.
Most patients experienced a reduction of the frequency, duration, and severity of attacks when receiving Cinryze compared to placebo. The response varied. Of the 22 patients who participated, 20 had fewer attacks on Cinryze, four had no attacks, but two had more attacks. These two, however, experienced shorter and less-severe attacks.
Cinryze was considered to be safe and effective. While on Cinryze, attacks lasted only 2.1 days (3.4 for placebo) and researchers observed a 66 percent reduction in days of swelling.