CSL wins FDA approval for ANDEMBRY, the first monthly anti-factor XIIa therapy for hereditary angioedema

What makes CSL’s ANDEMBRY the first-of-its-kind prophylactic HAE treatment approved by the U.S. FDA?

Global biotechnology developer CSL (ASX: CSL; USOTC: CSLLY) has received approval from the United States Food and Drug Administration for ANDEMBRY® (garadacimab-gxii), marking a new chapter in hereditary angioedema (HAE) treatment. This regulatory clearance makes ANDEMBRY the first and only prophylactic therapy to prevent HAE attacks by targeting activated factor XII (XIIa)—the topmost component of the HAE attack cascade. ANDEMBRY is also the only option available to all eligible patients, adults and adolescents aged 12 and older, with once-monthly subcutaneous dosing from the outset.

The approval affirms CSL’s strategic pivot toward next-generation biologics for rare and immunologic diseases, as well as the company’s four-decade commitment to HAE treatment innovation. Commercial availability in the United States is expected before the end of June 2025, with CSL Behring’s ANDEMBRY ConnectSM platform supporting access and onboarding for both physicians and patients.

How does factor XIIa inhibition differ from existing HAE therapies that target downstream pathways?

CSL’s ANDEMBRY represents a significant mechanistic shift in prophylactic HAE management. While existing therapies primarily inhibit downstream targets such as plasma kallikrein or bradykinin—molecules that amplify swelling after the cascade has begun—ANDEMBRY halts the process at its inception by neutralizing factor XIIa. Factor XII is the first protein activated in the HAE cascade. Its activated form, XIIa, sets off the series of reactions that ultimately cause bradykinin-induced vascular leakage and tissue swelling.

By blocking this upstream target, ANDEMBRY offers a preventive approach designed to eliminate swelling triggers before they escalate. According to CSL, this proactive mechanism could lead to higher attack-free rates and longer-term disease control than what is possible with current therapies that intervene midstream.

What clinical data from the VANGUARD trial supported the U.S. FDA’s approval decision for ANDEMBRY?

The approval is based on the pivotal Phase 3 VANGUARD trial, a randomized, placebo-controlled, double-blind study evaluating the efficacy and safety of ANDEMBRY in patients with HAE type I or II. Involving 64 patients across global sites, the trial compared monthly subcutaneous injections of 200 mg ANDEMBRY (following a 400 mg loading dose) with volume-matched placebo over a six-month treatment period.

Published in The Lancet in April 2023, the study revealed a median reduction in attack frequency of more than 99 percent among ANDEMBRY recipients. Additionally, the least squares mean reduction was 89.2 percent relative to placebo. Among patients treated with ANDEMBRY, 62 percent remained completely attack-free during the trial. The treatment also demonstrated a 99 percent median reduction in attacks requiring on-demand rescue medication, and moderate-to-severe attacks declined by 90 percent on average.

The most common adverse events included nasopharyngitis and abdominal pain, both occurring in 7 percent or more of the study population. Around 14 percent of patients experienced mild injection-site reactions such as bruising, erythema, pruritus, and urticaria. No new safety signals emerged in either the pivotal or extension phases, which experts believe strengthens the clinical case for broader adoption.

What did the open-label extension study reveal about long-term safety and efficacy of ANDEMBRY in HAE patients?

A published interim analysis from Allergy in October 2024 reported on the ongoing open-label extension of the VANGUARD study. At the time of analysis, patients had received a median of 13.8 months of ANDEMBRY exposure. The findings further supported a favorable safety and tolerability profile, as well as durable efficacy. Patients maintained low attack rates, with continued reductions in episodes requiring rescue intervention.

CSL emphasized that these data demonstrate sustained disease control in real-world conditions and bolster confidence in the product’s viability for long-term management. The open-label study remains active, tracking patient outcomes and safety over extended periods and across diverse HAE phenotypes.

How does CSL plan to support ANDEMBRY’s U.S. launch and expand access across global HAE markets?

Following FDA approval, CSL Behring has initiated its U.S. launch strategy with ANDEMBRY ConnectSM, a patient services hub aimed at streamlining access, reimbursement, and clinical onboarding. CSL has stated that the treatment will be distributed nationwide before the end of June 2025. Physicians, specialty pharmacies, and immunology clinics have been pre-briefed on prescribing logistics, and CSL expects strong initial demand among patients with frequent or severe HAE attacks.

ANDEMBRY had already received regulatory approval in multiple global jurisdictions, including the European Union, United Kingdom, Australia, Japan, Switzerland, and the United Arab Emirates. These international approvals position CSL to drive global revenue growth from the franchise while aligning with health authorities’ increasing emphasis on biologic innovation for rare diseases.

The U.S. launch is also seen as a precursor to broader formulary inclusion and potential health technology assessments in additional markets, especially in Latin America and Asia-Pacific where biologics uptake in hereditary angioedema is gaining momentum.

What is the commercial and strategic significance of ANDEMBRY for CSL’s biologics and immunology franchise?

ANDEMBRY marks a major inflection point for CSL’s internal R&D and commercial strategy. It is the first FDA-approved biologic entirely developed in-house by CSL scientists—from antibody discovery at the Bio21 research site in Melbourne to formulation and clinical manufacturing at the Broadmeadows Biotech Manufacturing Facility. The program showcases CSL’s ability to develop complex monoclonal antibodies targeting novel rare disease mechanisms and shepherd them through regulatory and commercial pathways.

Analysts have noted that CSL’s biologics segment is entering a pivotal growth phase. ANDEMBRY is expected to complement existing C1-INH and plasma-derived products, enabling the company to serve patients across multiple preference profiles—including those who require minimal injection frequency, novel mechanism of action, or reduced side effect burden.

For investors, the approval provides strategic optionality and diversification in CSL’s revenue mix. It also enhances CSL Behring’s competitive posture against existing HAE players such as Takeda and BioCryst Pharmaceuticals, both of which offer downstream-targeting therapies but not yet a factor XIIa-based prophylactic.

What are experts and advocacy groups saying about the impact of ANDEMBRY’s approval on the HAE treatment landscape?

Clinical and patient community leaders have responded positively to the FDA’s approval of ANDEMBRY. Dr. Tim Craig, a specialist in allergy and immunology at Penn State University, stated that the ability to inhibit the top of the HAE cascade introduces a new paradigm in disease management. He emphasized that while existing options have improved outcomes, the burden of frequent injections and breakthrough attacks persists for many patients.

Anthony Castaldo, Chairman of HAE International, underscored the value of having more choices for a lifelong disease that varies significantly in presentation and severity. He described ANDEMBRY as “a welcome addition” that could help many individuals achieve long-term control and better quality of life.

Institutional sentiment also appears cautiously optimistic. Given CSL’s extensive commercial infrastructure and experience in rare disease launches, analysts expect rapid adoption among high-need patient cohorts and favorable feedback from immunologists seeking differentiated therapeutic tools.

What is the future outlook for CSL’s HAE franchise and follow-on pipeline after ANDEMBRY’s FDA approval?

With ANDEMBRY now approved in the U.S. and multiple global regions, CSL is likely to pursue expanded indication studies and pediatric development programs. The open-label extension study will provide further safety and efficacy data, potentially supporting regulatory discussions for use in younger patients or those with atypical HAE presentations.

Additionally, factor XIIa as a therapeutic target may unlock research opportunities in adjacent bradykinin-mediated diseases, such as idiopathic angioedema or certain vascular inflammatory conditions. CSL’s success in developing a validated anti-FXIIa biologic could also inform its pipeline development in inflammation, hematology, and complement modulation.

In the broader immunology landscape, ANDEMBRY’s approval is expected to intensify innovation around upstream disease interruption, particularly in rare conditions with predictable biochemical triggers. CSL’s biologics capabilities now appear validated, and investors are likely to watch closely for next-generation pipeline candidates building on this success.