HYQVIA^® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase], the Only Once-a-Month – Every Three or Four Weeks – Subcutaneous Immunoglobulin (ScIG), is Now Approved for People Two Years of Age and Older with Primary Immunodeficiency
Approval Supported by Pivotal Phase 3 Study that Demonstrated Reliable Infection Protection in Children 2-16 Years Old

Takeda ((TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental biologics license application (sBLA) to expand the use of HYQVIA to treat primary immunodeficiency (PI) in children 2-16 years old. HYQVIA is the only subcutaneous immune globulin (ScIG) infusion that can be administered once a month – every three or four weeks – and was first approved in the U.S. in 2014 for the treatment of PI in adults.

PI is an umbrella term to describe a group of more than 400 disorders that affect the body's immune system, increasing susceptibility to infection.¹ Children living with PI and their families face distinct challenges as they are more likely to get frequent and serious infections that can impact their school attendance and ability to participate in social activities.² While immune globulin (IG) infusions can be effective at protecting against infections associated with a PI diagnosis, some therapy options may not be optimal for all children and their families. For example, intravenous route of administration may be difficult for some children and the frequency of some subcutaneous therapies may be challenging for some families' schedules.²

"Families of children living with primary immunodeficiency may feel overwhelmed by their child's chronic medical needs. When it comes to treatment, having choices can mean a great deal to families," said Jorey Berry, president and chief executive officer of the Immune Deficiency Foundation. "The approval of this new PI treatment for children 2 to 16 years old offers an alternative for health care providers and families who might prefer a less frequent treatment option that can be administered subcutaneously at home, after appropriate training, or in an infusion center."

The FDA approval of HYQVIA for the treatment of PI in pediatric patients was based on evidence from a pivotal, prospective, open-label, non-controlled Phase 3 clinical trial that included 44 PI patients between the ages of 2 and 16. Data were analyzed when all subjects completed 12 months of participation (one year of observation) in the trial. The data showed no clinically meaningful differences in trough Immunoglobulin G (IgG) levels across age groups. During the 12-month trial period, HYQVIA was shown to be efficacious with respect to the occurrence of acute serious bacterial infections (aSBIs), a primary endpoint. The mean aSBI rate per year was 0.04 and was statistically significantly lower (with an upper 1-sided 99% confidence interval of 0.21, p<0.001) than the predefined success rate of less than one aSBI per subject per year, favoring efficacy of HYQVIA treatment in pediatric subjects with PI diseases. The efficacy of HYQVIA in this study was further demonstrated by the overall rate of infections per subject, which is consistent with results obtained in the pivotal clinical study. The mean rate of all infections per subject-year was 3.20, with an upper limit of the 95% confidence interval of 4.05.³ Results from the interim data analysis, where all subjects completed 12 months of participation (one year of observation period) in the study, indicated similar safety profiles to adults.³

"This expanded HYQVIA indication exemplifies our ongoing commitment to providing plasma-derived therapies with proven efficacy. HYQVIA is now available to a broader community impacted by PI, including children and their families with distinct needs, who may prefer flexible treatment options in the management of these disorders," said Brandon Monk, head of Takeda's U.S. Plasma-Derived Therapies Business Unit.

About HYQVIA^® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase]

HYQVIA^® is a liquid medicine containing Recombinant Human Hyaluronidase and immunoglobulins (Ig) and approved in the United States to treat adults and children two years of age and older with primary immunodeficiency (PI). It is also approved in the European Union as a replacement therapy in adults, children and adolescents with PI and with secondary immunodeficiency (SID) who suffer from severe or recurrent infections, ineffective antimicrobial treatment, and either proven specific antibody failure (PSAF) or serum IgG level of <4 g/L. HYQVIA is infused under the skin into the fatty subcutaneous tissue. HYQVIA contains immunoglobulins collected from human plasma. Immunoglobulins are antibodies that maintain the body's immune system. The hyaluronidase part of HYQVIA helps more of the Ig get absorbed into the body. HYQVIA is infused up to once a month (every three or four weeks).

Resources Available to Patients

For more information about HYQVIA, please call 1-877-TAKEDA-7 (1-877-825-3327).

HYQVIA U.S. Indication and Limitation of Use

HYQVIA is indicated for the treatment of primary immunodeficiency (PI) in adults and pediatric patients two years of age and older. HYQVIA is for subcutaneous use only. Safety and efficacy of chronic use of Recombinant Human Hyaluronidase in HYQVIA have not been established in conditions other than PI.

HYQVIA U.S. Important Safety Information

WARNING: THROMBOSIS

Thrombosis may occur with immune globulin (IG) products, including HYQVIA. Risk factors may include advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors.
For patients at risk of thrombosis, administer HYQVIA at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration.
Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk of hyperviscosity.

Contraindications

History of anaphylactic or severe systemic hypersensitivity reactions to human IG
IgA-deficient patients with antibodies to IgA and a history of hypersensitivity to human IG
Known systemic hypersensitivity to hyaluronidase including Recombinant Human Hyaluronidase of HYQVIA
Known systemic hypersensitivity to human albumin (in the hyaluronidase solution)

Warnings and Precautions

Hypersensitivity: Severe hypersensitivity reactions may occur, even in patients who have tolerated previous treatment with human IG. 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.
Thrombosis: Has been reported to occur following treatment with IG products, including HYQVIA, 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.
Immunogenicity of Recombinant Human Hyaluronidase (rHuPH20): Non-neutralizing antibodies to the Recombinant Human Hyaluronidase component can develop. The clinical significance of these antibodies or whether they interfere with fertilization in humans is unknown.
Aseptic Meningitis Syndrome: Has been reported with use of IG, including HYQVIA, and may occur more frequently in females. The syndrome usually begins within several hours to two days following IG treatment. 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.
Hemolysis: HYQVIA contains 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.
Renal Dysfunction/Failure: Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis and death may occur with intravenous (IV) use of IG products, especially those containing sucrose. 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.
Spread of Localized Infection: Do not infuse HYQVIA into or around an infected area due to potential risk of spreading a localized infection.
Transfusion-Related Acute Lung Injury: Non-cardiogenic pulmonary edema may occur with IV administered IG. 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 HYQVIA is made from human plasma, it may carry a risk of transmitting infectious agents (e.g., viruses, other pathogens). No cases of transmission of viral diseases or variant Creutzfeldt-Jakob disease (vCJD) have been associated with HYQVIA.
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.

Adverse Reactions

The most common adverse reactions observed in >5% of patients in the clinical trials were: local adverse reactions including pain, erythema, edema, and pruritus, and systemic adverse reactions including, headache, antibody formation against Recombinant Human Hyaluronidase (rHuPH20), fatigue, nausea, pyrexia, and vomiting.

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).

Use In Specific Populations

Pregnancy: Limited human data are available on the use of HYQVIA during pregnancy. The effects of antibodies to the Recombinant Human Hyaluronidase on the human embryo or fetal development are unknown. It is not known whether HYQVIA can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity. HYQVIA should be given to a pregnant woman only if clearly needed.

For Full U.S. Prescribing Information, please visit: https://www.shirecontent.com/PI/PDFs/HYQVIA_USA_ENG.pdf

About Primary Immunodeficiency

Primary immunodeficiency is not a single condition; it's a group of more than 400 rare, chronic disorders that disrupt the body's immune system from functioning properly.¹ These conditions are often inherited; however, some of the disorders are also caused by genetic and environmental factors.¹ In the United States, PI affects about 1 in 1,200 people.¹ People with PI often face increased susceptibility to infections, repeated infections, and infections that are difficult to treat.¹

About Takeda

Takeda is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI), with expertise in immune and inflammatory diseases. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions. For more information, visit https://www.takeda.com.

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References

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¹ Immune Deficiency Foundation. About Primary Immunodeficiencies. Accessed May 11, 2021. www.primaryimmune.org/about-primary-immunodeficiencies.

² Ballow, M., Heimall, J., Epland, K., Leiding, J., Perez, E., Riedl, M., & Younger, E. M. Patient & Family Handbook for Primary Immunodeficiency Diseases. Immune Deficiency Foundation;2019. p.199-204.

³ HYQVIA [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] U.S. Prescribing Information.

US-HYQ-0557v1.0 04/23

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