U.S. Food and Drug Administration Approves CSL's ANDEMBRY® (garadacimab-gxii), the Only Prophylactic Hereditary Angioedema (HAE) Treatment Targeting Factor XIIa with Once-Monthly Dosing for All Patients From the Start

Rhea-AI Summary

CSL (CSLLY) has received FDA approval for ANDEMBRY (garadacimab-gxii), a groundbreaking treatment for hereditary angioedema (HAE) in patients aged 12 and older. ANDEMBRY is the first and only factor XIIa-targeting prophylactic treatment offering once-monthly dosing via a citrate-free autoinjector. The Phase 3 VANGUARD trial demonstrated exceptional efficacy, with 62% of patients remaining attack-free and a median reduction in HAE attacks of over 99% compared to placebo. The treatment showed a favorable safety profile, with nasopharyngitis and abdominal pain as the most common side effects. ANDEMBRY has already received approvals in multiple jurisdictions including Australia, UK, EU, Japan, Switzerland, and UAE, with immediate commercial launch planned in the US before the end of June 2025.

Positive

• First-in-class treatment targeting factor XIIa with once-monthly dosing convenience
• Exceptional efficacy with 62% of patients remaining attack-free during treatment
• Impressive 99% median reduction in HAE attacks compared to placebo
• Already approved in multiple major markets with immediate US commercial launch
• Favorable long-term safety profile demonstrated in extension studies

Negative

• 14% of patients experienced injection-site reactions in clinical trials
• Limited to patients aged 12 and older

• ANDEMBRY inhibits the top of the HAE cascade by targeting factor XIIa and provides sustained protection from attacks
• Once-monthly dosing reduced HAE attacks by a median of more than 99 percent and a least squares mean of 89.2 percent, compared to placebo
• ANDEMBRY approval expands CSL's HAE franchise and underscores the company's legacy of delivering transformational innovations to the HAE community for over four decades

KING OF PRUSSIA, Pa., June 16, 2025 /PRNewswire/ -- Global biotechnology leader CSL (ASX:CSL; USOTC:CSLLY) today announced the U.S. Food and Drug Administration (FDA) approved ANDEMBRY^® (garadacimab-gxii), the only treatment targeting factor XIIa for prophylactic use to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. By targeting factor XIIa, a plasma protein that plays a key role in attacks of swelling in people with HAE, ANDEMBRY inhibits the top of the HAE cascade to prevent HAE attacks. ANDEMBRY, the only treatment to offer once-monthly dosing from the start for all patients, is a subcutaneous self-injection delivered in 15 seconds or less via an autoinjector with a citrate-free formula.

HAE is a rare, chronic, and potentially life-threatening genetic disorder characterized by recurrent and unpredictable attacks of angioedema. Attacks of HAE are often painful and can affect multiple sites of the body, including the abdomen, larynx, face, and extremities. HAE occurs in about 1 in 50,000 people of any ethnic group.

"ANDEMBRY, the first monoclonal antibody discovered and developed entirely by CSL, offers people living with this life-threatening condition long-term control over their disease along with a convenient administration method," said Bill Mezzanotte, MD, Executive Vice President, Head of R&D, CSL. "ANDEMBRY underscores our long-standing and enduring commitment to better the lives of the patients we serve, including those suffering with HAE. I'd like to thank all the physicians, patients and my colleagues who contributed to this exciting milestone for HAE patients and CSL."

The approval is supported by data from the pivotal placebo-controlled Phase 3 VANGUARD trial evaluating the efficacy and safety of ANDEMBRY. The pivotal study (The Lancet, April 2023) demonstrated that treatment with ANDEMBRY:

• Led to 62 percent of ANDEMBRY-treated patients remaining attack-free throughout the treatment period.
• Reduced HAE attacks by a median of more than 99 percent and a least squares mean of 89.2 percent, compared to placebo.
• Achieved more than 99 percent median reduction and an 88 percent mean reduction in HAE attacks requiring on-demand therapy, compared to placebo.
• Attained more than 99 percent median reduction and a 90 percent mean reduction in moderate or severe attacks, compared to placebo.
• The most common adverse reactions in the pivotal trial (incidence ≥7%) are nasopharyngitis and abdominal pain.

A published interim analysis (Allergy, Oct 2024) of the ongoing open-label extension study (median ANDEMBRY exposure of 13.8 months) showed that ANDEMBRY has a favorable long-term safety profile and provides sustained reductions in HAE attacks. In the pivotal trial and the open-label extension study, injection-site reactions (e.g., injection-site bruising, injection-site erythema, injection-site hematoma, injection-site pruritus, injection-site urticaria) were reported in 23 (14%) patients.

"We've made significant progress in treating hereditary angioedema, yet many patients still experience painful and sometimes life-threatening HAE attacks and require frequent injections to manage them," said Dr. Tim Craig, Professor of Medicine, Pediatrics and Biomedical Sciences at Penn State University. "We now have a new option to manage this condition through a new target, as it allows us for the first time to inhibit the top of the HAE cascade by targeting factor XIIa."

"ANDEMBRY, a novel once-monthly subcutaneous treatment that inhibits factor XIIa, is a welcome addition to the HAE treatment landscape," said Anthony J. Castaldo, CEO and Chairman of the Board, US HAE Association and HAE International. "People with HAE now have another choice for lessening the burden associated with this lifelong condition and realizing the community's shared goal of experiencing life to the fullest."

This regulatory approval for ANDEMBRY is another crucial step in building toward the global availability of ANDEMBRY, which was recently approved in Australia, the United Kingdon (UK), the European Union (EU), Japan, Switzerland, and United Arab Emirates. 

CSL Behring will launch ANDEMBRY commercially immediately, with availability before the end of June. Healthcare professionals and patients interested in learning more about ANDEMBRY or accessing the therapy are encouraged to utilize ANDEMBRY Connect^SM, designed to offer comprehensive support and assistance through various programs. For more information, call 844-423-4273 or visit www.ANDEMBRY.com. 

About HAE 
HAE is a rare and potentially life-threatening genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people. HAE is caused by deficient or dysfunctional C1INH, a protein in the blood that helps to control inflammation. Inadequate amounts of properly functioning C1INH can lead to the accumulation of fluid in body tissues, causing considerable swelling referred to as angioedema. HAE attacks can affect many parts of the body, including the face, abdomen, larynx, and extremities. Patients who have abdominal attacks of HAE can experience extreme pain, diarrhea, nausea, and vomiting caused by swelling of the intestinal wall. HAE attacks that involve the face or throat can result in airway closure, asphyxiation and, if left untreated, death.

About ANDEMBRY
ANDEMBRY is a novel monoclonal antibody inhibiting factor XIIa (anti-FXIIa mAb) that has completed the Phase 3 pivotal study as a new type of once-monthly subcutaneous prophylactic treatment for attacks related to HAE, a form of bradykinin-mediated angioedema. ANDEMBRY is CSL's first homegrown recombinant monoclonal antibody to gain FDA approval. It was discovered and optimized by scientists at CSL's Bio21-based research site, with formulation and manufacturing for the clinical programs completed at the CSL Broadmeadows Biotech Manufacturing Facility. ANDEMBRY uniquely inhibits the plasma protein, FXIIa. FXII is the first protein activated in the HAE pathway, initiating the cascade of events leading to an HAE attack. By targeting activated FXII (FXIIa), ANDEMBRY inhibits this cascade at the top as compared to other HAE therapies that target downstream mediators.

About the VANGUARD Trial 
The multicenter, randomized, double-blind, parallel-group VANGUARD trial evaluated the efficacy and safety of ANDEMBRY, an investigational first-in-class monoclonal antibody, as a prophylactic treatment for patients with hereditary angioedema. Patients aged 12 years and older with HAE type I or II underwent screening and a run-in study period to verify a baseline attack rate. Patients were randomized 3:2 to receive a loading dose of 400 mg followed by 200 mg of ANDEMBRY monthly (n=39) or volume matched placebo monthly (n=25) subcutaneously. After the six-month treatment period, patients were given the opportunity to continue into the open-label extension study, which is currently ongoing.

The ongoing open-label extension of the Phase 3 VANGUARD study is evaluating the long-term safety and efficacy of ANDEMBRY (200 mg monthly) for the prophylactic treatment of hereditary angioedema attacks.

IMPORTANT SAFETY INFORMATION

What is ANDEMBRY?
ANDEMBRY^® (garadacimab-gxii) injection, for subcutaneous use, is a prescription medication used to prevent attacks of hereditary angioedema (HAE) in people 12 years and older.

It is not known if ANDEMBRY is safe and effective in children under 12 years of age.

What should I tell my healthcare provider before using ANDEMBRY?
Before using ANDEMBRY, tell your healthcare provider about any medical condition you may have, especially if you are pregnant, planning to become pregnant, breastfeeding, or planning to breastfeed. It is not known if ANDEMBRY can harm your unborn baby or if ANDEMBRY passes into breastmilk. Talk to your healthcare provider about the best way to feed your baby while using ANDEMBRY.

Tell your healthcare provider about all medications you take, including prescription medicines, over-the-counter treatments, vitamins, and herbal supplements.

How should I use ANDEMBRY? 
Use ANDEMBRY exactly as instructed by your healthcare provider. Detailed instructions for use can be found in the patient information section of the full prescribing information.

ANDEMBRY is given as an injection under your skin (subcutaneous) by you or a caregiver. Your healthcare provider should show you or your caregiver how to prepare and inject your dose of ANDEMBRY before you inject yourself for the first time. Do not try to inject ANDEMBRY unless you have been trained by your healthcare provider.

What are the possible side effects of ANDEMBRY?
The most common side effects of ANDEMBRY include:

• Redness, itchiness, and bruising (injection-site reactions)
• Stomach (abdominal) pain
• Runny or stuffy nose, sneezing, watery eyes (nasopharyngitis)

Please see full prescribing information for ANDEMBRY, including patient information and instructions for use.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

You can also report side effects to CSL Behring's Pharmacovigilance Department at 1-866-915-6958.

About CSL
CSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses: CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 32,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest.

For more information about CSL, visit www.CSL.com.

Media Contacts
Valerie Bomberger
CSL
Office: +1 610-291-5388 
Mobile: +1 267-280-3829 
Email: valerie.bomberger@cslbehring.com 

Etanjalie Ayala 
CSL Behring
Mobile: +1 610 297 1069 
Email: etanjalie.ayala@cslbehring.com

Greg Healy
CSL
Mobile: +1 610-906-4564
Email: greg.healy@cslbehring.com

In Australia: 
Kim O'Donohue
CSL
Mobile: +61 449 884 603
Email: kim.odonohue@csl.com.au

Brett Foley
CSL
Mobile: +61 461 464 708
Email: brett.foley@csl.com.au

Investors Contact
Chris Cooper
CSL
Mobile: +61 455 022 740
Email: chris.cooper@csl.com.au

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FAQ

What is ANDEMBRY and what did the FDA approve it for?

ANDEMBRY is a prophylactic treatment for hereditary angioedema (HAE) approved by the FDA for preventing attacks in patients 12 years and older. It is the first treatment targeting factor XIIa with once-monthly dosing.

How effective is ANDEMBRY in treating HAE based on clinical trials?

In clinical trials, ANDEMBRY reduced HAE attacks by over 99% (median) compared to placebo, with 62% of treated patients remaining completely attack-free throughout the treatment period.

What are the main side effects of ANDEMBRY?

The most common side effects include nasopharyngitis and abdominal pain. Additionally, 14% of patients experienced injection-site reactions such as bruising, erythema, hematoma, pruritus, and urticaria.

When will ANDEMBRY be available in the US market?

CSL plans to launch ANDEMBRY commercially immediately, with availability before the end of June 2025.

How is ANDEMBRY administered to patients?

ANDEMBRY is administered as a subcutaneous self-injection once monthly using an autoinjector with a citrate-free formula, taking 15 seconds or less to deliver.