Hereditary Angioedema Drug From CSL Gains German Backing

The hereditary angioedema (HAE) treatment landscape continues to evolve, with a significant development as Germany’s Institute for Quality and Efficiency in Health Care (IQWiG) has rendered a positive benefit assessment for CSL Behring’s garadacimab. Garadacimab, a first-in-class, subcutaneous inhibitor of activated factor XII (FXIIa), sets a new benchmark in HAE prophylaxis through its differentiated mechanism of action and monthly dosing convenience.

Hereditary angioedema is a rare, genetic disorder characterized by unpredictable, potentially life-threatening swelling attacks. Current standards of care for HAE have focused predominantly on C1 inhibitor replacement and kallikrein inhibition. Garadacimab, leveraging a novel FXIIa inhibition pathway, addresses a mechanistic gap and offers a once-monthly, subcutaneous administration that can be self-injected by patients, an attractive differentiation for both adherence and quality-of-life outcomes. The phase 3 VANGUARD trial provided the foundation for IQWiG’s benefit assessment, demonstrating a substantial reduction in monthly attack rates and meaningful improvements in general health metrics.

The IQWiG’s positive opinion elevates the competitive bar for hereditary angioedema therapies in Germany, notably as it is the first time an HAE product has been shown to provide additional benefit via indirect comparison in the German AMNOG process. This outcome builds upon garadacimab’s recent regulatory successes, including approval by the US FDA, European Commission, and Japanese authorities between February and June 2025. These convergent regulatory milestones reinforce the strength of garadacimab’s clinical data package, as well as the industry’s shifting focus to differentiated, patient-centric delivery modalities.

CSL Behring underscores a continuing legacy of innovation in rare disease and plasma protein therapeutics. CSL Behring’s Berinert (C1-Inhibitor) secured expanded European marketing authorizations for acute HAE attacks in 23 countries as early as 2008-2010, based on large-scale, multicenter controlled studies. More recently, the company’s HEMGENIX (etranacogene dezaparvovec) gene therapy for hemophilia B achieved direct access and payer landmark decisions across France, Austria, and the UK, demonstrating CSL Behring’s sophisticated market access and evidence generation strategy in both rare and ultra-rare indications. These precedents are instructive for the HAE space, highlighting payers’ increasing demands for robust comparative effectiveness data and patient-reported outcomes to support additional benefit claims and premium reimbursement positions.

The pending decision by Germany’s Federal Joint Committee (G-BA) on reimbursement, expected by late August, will be closely monitored by the pharma industry. A favorable outcome could establish a broader precedent for innovative hereditary angioedema therapies seeking to differentiate through new mechanisms, monthly dosing, and indirect comparative methodologies. IQWiG’s willingness to accept robust indirect comparisons, even in the absence of patient-level comparator data, sets a regulatory signal for future rare disease submissions and post-approval evidence strategies.

More broadly, the HAE therapy market, valued at over USD 5 billion in 2024 with a projected CAGR above 9.5%, is expected to see increased adoption of long-term prophylaxis and self-administration paradigms. Garadacimab’s standing as the only once-monthly, factor XIIa-targeted agent distinguishes it within both clinical guidelines and payer evaluations, not only in Germany but across major global markets that have recently adopted the product.