CHMP positive for Andembry ( garadacimab) as a once-monthly prophylactic treatment for hereditary angioedema (HAE) in adult and adolescent patients aged 12 years and older..- CSL Behring

 Global biotechnology leader CSL  announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending granting a marketing authorization for garadacimab as a once-monthly prophylactic treatment for hereditary angioedema (HAE) in adult and adolescent patients aged 12 years and older. Garadacimab is a monoclonal antibody that targets activated factor XII (factor XIIa), a plasma protein that plays a key role in attacks of swelling in people with HAE, thereby inhibiting the HAE cascade at the top to prevent HAE attacks. The final European Commission (EC) decision is expected in Q1 2025.

"CSL has a longstanding and relentless patient-focused approach to developing transformational medicines in areas of unmet need. This CHMP decision brings us closer to offering an innovative treatment to patients living with HAE, which is a debilitating and potentially life-threatening condition," said Emmanuelle Lecomte-Brisset, Senior Vice President and Head of Global Regulatory Affairs, CSL. "We look forward to making this therapy available to patients in Europe."

Attacks of HAE are often painful and can spread to multiple sites of the body, including the abdomen, larynx, face, and extremities. Current HAE preventive therapies work at various downstream steps in the cascade, but none prevent the cascade at its start.

The CHMP positive opinion is based on data from the pivotal placebo-controlled Phase III VANGUARD trial and its open-label extension study, both evaluating the efficacy and safety of garadacimab. The pivotal study met its primary endpoint and showed that garadacimab led to 62 percent of patients achieving attack-free status throughout the treatment period, reduced the median number of HAE attacks to zero and reduced the mean number of HAE attacks per month by 86.5 percent compared to placebo. Interim analysis of the ongoing open-label extension study (median garadacimab exposure 13.8 months) showed that garadacimab has a favorable long-term safety profile and provides sustained HAE attack reduction. The full results from VANGUARD were published in The Lancet (April 2023) and the primary results of the ongoing open-label extension study were published in Allergy (October 2024).

Citation: Volume 401, Issue 10382p1079-1090 April 01, 2023. "Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase III trial ". Prof Timothy J Craig, DO ∙ Avner Reshef, MD ∙ H Henry Li, MD ∙ Joshua S Jacobs, MD ∙ Prof Jonathan A Bernstein, MD ∙ Prof Henriette Farkas, PhD∙ et al.

Citation: Allergy . 2024 Oct 7.. doi: 10.1111/all.16351. Online ahead of print. "Long-term safety and efficacy of garadacimab for preventing hereditary angioedema attacks: Phase III open-label extension study". Avner Reshef ^, Connie Hsu  , Constance H Katelaris , Philip H Li ^, Markus Magerl , Keiko Yamagami , Mar Guilarte , Paul K Keith , Jonathan A Bernstein ^{, El al.  ,} ; VANGUARD Study Group. PMID: 39370961 ; DOI: 10.1111/all.16351.