Takeda Announces U.S. FDA Approval of GAMMAGARD LIQUID ERC, the Only Ready-to-Use Liquid Immunoglobulin Therapy with Low Immunoglobulin A (IgA) Content1

OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved GAMMAGARD LIQUID ERC [immune globulin infusion (human)] with less than or equal to 2 µg/mL IgA in a 10% solution, the only ready-to-use liquid immunoglobulin (IG) therapy with low immunoglobulin A (IgA) content, as replacement therapy for people two years of age and older with primary immunodeficiency (PI). As a ready-to-use liquid, GAMMAGARD LIQUID ERC may help ease the administration burden for patients and their health care providers by eliminating the need for reconstitution and can be administered intravenously or subcutaneously.1

“The approval of GAMMAGARD LIQUID ERC reinforces our commitment to supporting individualized treatment approaches for people with primary immunodeficiency, including a therapeutic option that has the lowest IgA content of any ready-to-use liquid immunoglobulin therapy, and can be administered intravenously or subcutaneously,” said Kristina Allikmets, senior vice president and head of Research & Development for Takeda’s Plasma-Derived Therapies Business Unit. “GAMMAGARD LIQUID ERC uses the same state-of-the-art manufacturing process as our other ready-to-use liquid immunoglobulin formulations and is aligned with our forward-looking strategy to prioritize reliable supply while offering a broad range of immunoglobulin therapies to address varied patient needs.”

With this approval, Takeda continues to be the only manufacturer of IG therapy with low IgA content less than or equal to 2 µg/mL in a 10% solution.1 It is anticipated that commercialization of GAMMAGARD LIQUID ERC will begin in the U.S. in 2026, followed by the European Union in 2027, where GAMMAGARD LIQUID ERC is approved by the European Medicines Agency (EMA) as DEQSIGA®.3 The timeline to commercial launch is consistent with the time it takes to ramp up manufacturing and supply for plasma-derived therapies.

In parallel to this approval, and after thorough analysis, Takeda has decided to discontinue GAMMAGARD S/D [Immune Globulin Intravenous (Human)] IgA less than 1 µg/mL in a 5% solution, the company’s first-generation low IgA product.2 As the only lyophilized (freeze-dried) preparation in Takeda’s IG portfolio, GAMMAGARD S/D uses a different, older manufacturing process. For GAMMAGARD S/D, this process is no longer able to reliably meet the future needs of the patient community. Therefore, Takeda has informed the FDA and other health authorities that manufacturing of GAMMAGARD S/D will be discontinued at the end of December 2027. Beyond that date, Takeda intends to maintain GAMMAGARD S/D inventory until it is depleted or expired.

“We understand the impact that this news may have on patients who currently rely on GAMMAGARD S/D for their treatment,” said Kristina Allikmets. “We are communicating this information now to allow time for patients to work closely with their health care teams to develop alternative treatment plans.”

About GAMMAGARD LIQUID ERC
GAMMAGARD LIQUID ERC is a ready-to-use liquid immunoglobulin therapy with an IgA content of less than or equal to 2 µg/mL in a 10% solution to be administered intravenously or subcutaneously. It is indicated in the United States as replacement therapy for primary immunodeficiency (PI) in people two years of age and older.1

GAMMAGARD LIQUID ERC shares its manufacturing process with GAMMAGARD LIQUID [Immune Globulin Infusion (Human)], with the modification of parameters in a single process step to improve IgA reduction. This enhanced removal capability (ERC) results in a product with IgA less than or equal to 2 µg/mL in a 10% solution.1

While GAMMAGARD LIQUID ERC is not indicated specifically for IgA sensitivity in people with primary immunodeficiency, it may be an appropriate option for them based on their physician’s clinical judgment. GAMMAGARD LIQUID ERC is contraindicated in patients with a history of severe systemic hypersensitivity or anaphylactic reactions to the product. It also carries warnings and precautions regarding the potential for severe hypersensitivity reactions, including in patients who have previously tolerated immune globulin products. Despite containing low levels of IgA (≤2 µg/mL in a 10% solution), the risk of anaphylaxis remains.1

About GAMMAGARD S/D
GAMMAGARD S/D is lyophilized (freeze-dried) immunoglobulin therapy with IgA content less than 1 µg/mL in a 5% solution for intravenous use only. It is indicated for the treatment of primary immunodeficiency (PI) in adults and pediatric patients 2 years and older. GAMMAGARD S/D is also indicated for prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell CLL, for the treatment of adult patients with chronic immune thrombocytopenic purpura (ITP) to increase platelet count and to prevent and/or to control bleeding, and for the prevention of coronary artery aneurysms associated with Kawasaki syndrome in pediatric patients.2

About Primary Immunodeficiency (PI)
Primary immunodeficiency (PI) is a group of more than 550 rare and chronic disorders, where a part of the body’s immune system is missing or does not function the way it should.4 These conditions result from genetic mutations, which are usually inherited.5 The symptoms of PI vary and can include frequent and/or persistent infections and unusual autoimmunity, often leading to prolonged periods of misdiagnosis despite consultations with multiple specialists.6 In the United States, PI affects about 1 in 1,200 people.7

GAMMAGARD LIQUID ERC, GAMMAGARD LIQUID and GAMMAGARD S/D U.S. Important Safety Information

Contraindications

• GAMMAGARD LIQUID is contraindicated in patients with a history of anaphylactic or severe systemic hypersensitivity reactions to human IG, and IgA-deficient patients with antibodies to IgA and a history of hypersensitivity to human IG. Anaphylaxis has been reported with intravenous (IV) use of GAMMAGARD LIQUID.
• GAMMAGARD LIQUID ERC and GAMMAGARD S/D are contraindicated in patients with a history of anaphylactic or severe systemic hypersensitivity reactions to the administration of GAMMAGARD LIQUID ERC and GAMMAGARD S/D.

Warnings and Precautions

Hypersensitivity: Severe hypersensitivity reactions may occur, even in patients who have tolerated previous treatment with human IG. Severe hypersensitivity reactions and anaphylactic reactions with a fall in blood pressure have occurred in patients receiving GAMMAGARD S/D, including patients who tolerated previous treatments with GAMMAGARD S/D, even though it contains low levels of IgA. If a hypersensitivity reaction occurs, discontinue infusion immediately and institute appropriate treatment. IgA-deficient patients with antibodies to IgA are at greater risk of developing potentially severe hypersensitivity reactions, including anaphylaxis.

Renal Dysfunction/Failure: Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, and death may occur with IV use of IG products, especially those containing sucrose. Acute renal failure has been reported in association with GAMMAGARD LIQUID and GAMMAGARD S/D. Ensure patients are not volume depleted prior to infusion. In patients at risk due to pre-existing renal insufficiency or predisposition to acute renal failure, assess renal function before initiation and throughout treatment, and consider lower, more frequent dosing. If renal function deteriorates, consider discontinuation.

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur. It is critical to distinguish true hyponatremia from pseudohyponatremia because certain treatments may lead to volume depletion, a further increase in serum viscosity, and a predisposition to thromboembolic events.

Thrombosis: Has been reported to occur following treatment with IG products and in the absence of known risk factors. In patients at risk, administer at the minimum dose and infusion rate practicable. Ensure adequate hydration before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

Aseptic Meningitis Syndrome: Has been reported with use of IG. Conduct a thorough neurological exam on patients exhibiting signs and symptoms, to rule out other causes of meningitis. Discontinuing IG treatment has resulted in remission within several days without sequelae. The syndrome usually begins within several hours to two days following IG treatment

Hemolysis: GAMMAGARD LIQUID, GAMMAGARD LIQUID ERC, and GAMMAGARD S/D contain blood group antibodies, which may cause a positive direct antiglobulin reaction and hemolysis. Monitor patients for signs and symptoms of hemolysis and delayed hemolytic anemia and, if present, perform appropriate confirmatory lab testing.

Transfusion-Related Acute Lung Injury: Non-cardiogenic pulmonary edema has been reported with IV-administered IG, including GAMMAGARD LIQUID. Monitor patients for pulmonary adverse reactions. If suspected, perform appropriate tests for presence of anti-neutrophil and anti-HLA antibodies in both product and patient serum. May be managed using oxygen therapy with adequate ventilatory support.

Transmittable Infectious Agents: Because GAMMAGARD LIQUID, GAMMAGARD LIQUID ERC, and GAMMAGARD S/D are made from human plasma, they may carry a risk of transmitting infectious agents (e.g., viruses, other pathogens). No confirmed cases of viral transmission or variant Creutzfeldt-Jakob disease (vCJD) have been associated with GAMMAGARD LIQUID.

Interference with Lab Tests: False positive serological test results and certain assay readings, with the potential for misleading interpretation, may occur as the result of passively transferred antibodies.

Alterations in serum sodium levels (i.e., acute hypernatremia, pseudohyponatremia) may occur with GAMMAGARD S/D. In patients on a low sodium diet, calculate the amount of sodium from GAMMAGARD S/D when determining dietary sodium intake.

Adverse Reactions

GAMMAGARD LIQUID

IV administration: The serious adverse reaction seen during IV clinical trials was aseptic meningitis. The most common adverse reactions observed in ≥5% of patients in clinical trials were headache, fatigue, pyrexia, nausea, chills, rigors, pain in extremity, diarrhea, migraine, dizziness, vomiting, cough, urticaria, asthma, pharyngolaryngeal pain, rash, arthralgia, myalgia, oedema peripheral, pruritus, and cardiac murmur.

Subcutaneous administration: The most common adverse reactions observed in ≥5% of patients in clinical trials were infusion site (local) event (rash, erythema, edema, hemorrhage, and irritation), headache, fatigue, heart rate increased, pyrexia, abdominal pain upper, nausea, vomiting, asthma, blood pressure systolic increased, diarrhea, ear pain, aphthous stomatitis, migraine, oropharyngeal pain, and pain in extremity.

GAMMAGARD LIQUID ERC

The safety of GAMMAGARD LIQUID ERC in patients with primary humoral immunodeficiency (PI) is supported by two clinical studies conducted on GAMMAGARD LIQUID. No clinical studies have been conducted using GAMMAGARD LIQUID ERC.

IV administration: The most common adverse reactions observed in ≥5% of patients in study 1 were headache, fatigue, pyrexia, chills, nausea, pain in extremity, diarrhea, migraine, vomiting, dizziness, urticaria, cough, asthma, oropharyngeal pain, infusion site extravasation, arthralgia, rash, myalgia, pruritis, and cardiac murmur.

Subcutaneous administration: The most common adverse reactions observed in ≥5% of patients in study 2 were infusion site (local) event, headache, pyrexia, fatigue, heart rate increased, abdominal pain upper, vomiting, arthralgia, nausea, asthma, blood pressure systolic increased, diarrhea, ear pain, aphthous ulcer, migraine, oropharyngeal pain, and pain in extremity.

GAMMAGARD S/D

The most common adverse reactions observed in ≥5% of clinical trial patients during or within 48 hours of infusion were headache, nausea, chills, fatigue, pyrexia, upper abdominal pain, diarrhea, back pain, infusion site pain, hyperhidrosis, and flushing.

The most serious adverse reactions reported postmarketing include renal failure, thrombotic events (myocardial infarction, cerebrovascular accidents, and pulmonary embolism), anaphylactic shock, aseptic meningitis, and hemolysis.

Drug Interactions

Passive transfer of antibodies may transiently interfere with the immune responses to live attenuated virus vaccines (e.g., measles, mumps, rubella, and varicella).

For Full U.S. Prescribing Information for GAMMAGARD LIQUID, please visit: https://www.shirecontent.com/PI/PDFs/GAMLIQUID_USA_ENG.pdf

For Full U.S. Prescribing Information for GAMMAGARD LIQUID ERC, please visit: https://content.takeda.com/?contenttype=PI&product=GAM&language=ENG&country=USA&documentnumber=2

For Full U.S. Prescribing Information for GAMMAGARD S/D, please visit: https://www.shirecontent.com/PI/PDFs/GGSD_USA_ENG.pdf

For European Union Summary of Product Characteristics for DEQSIGA, please visit: https://www.ema.europa.eu/en/medicines/human/EPAR/deqsiga

About Takeda
Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.

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