Takeda Announces Positive Topline Results from Pivotal Phase 2/3 Clinical Trial of TAK-881 in Primary Immunodeficiency Disease (PID)

• Investigational TAK-881 was comparable to established HYQVIA while also demonstrating reduced infusion volume and duration for PID patients

Takeda ((TAK) today announced that TAK-881-3001, a pivotal Phase 2/3 clinical trial in patients with Primary Immunodeficiency Disease (PID), met its primary endpoint, which demonstrated pharmacokinetic (PK) comparability between the investigational TAK-881 [Immune Globulin Subcutaneous (Human), 20% Solution (SCIG 20%) with Recombinant Human Hyaluronidase] and HYQVIA [Immune Globulin Infusion (Human) 10% with Recombinant Human Hyaluronidase]. Additionally, secondary endpoints showed that TAK-881, a SCIG 20% facilitated with hyaluronidase, demonstrated safety, efficacy and tolerability profiles comparable to HYQVIA, an established SCIG 10% facilitated with hyaluronidase. These findings support the potential of TAK-881 to deliver the required immunoglobulin (IG) dose for PID patients in half the volume of HYQVIA, reducing infusion duration while maintaining flexible, up to once-monthly dosing for patients (every three or four weeks for PID).

The TAK-881-3001 clinical trial evaluated the PK, efficacy, safety, tolerability and immunogenicity of TAK-881 in adults and pediatric patients aged 2 years and older with PID previously treated with IG therapy and compared them with HYQVIA in patients aged 16 years and older. Initial topline data show TAK-881:

• Achieved comparable PK: The study met its primary endpoint demonstrating equivalent immunoglobulin G (IgG) exposure between TAK-881 and HYQVIA as shown by a geometric mean ratio of 99.67% (90% CI: 95.10% to 104.46%) for the areas under the concentration-time profiles over one dosing interval at the steady state (AUC_0-tau,ss).
• Provided immune protection: TAK‑881 demonstrated comparable infection rates and immune protection to HYQVIA, with protective IgG levels consistently maintained throughout the study.
• Demonstrated a comparable safety profile: The safety and tolerability profiles of TAK-881 shown were comparable to HYQVIA, with no new safety signals observed. The safety profile of TAK-881 will continue to be evaluated in the ongoing TAK-881-3002 extension study.

"These Phase 2/3 results showed the pharmacokinetic profile of TAK-881 was comparable to HYQVIA, an established IG standard of care in patients with PID, while offering the potential advantages of fewer injection sites, a flexible treatment schedule and shorter infusion times," said Kristina Allikmets, MD, PhD, Senior Vice President and Head of Plasma Derived Therapies R&D at Takeda. "TAK-881-3001 reflects our broader R&D commitment to advancing next-generation IG therapies and bringing meaningful new treatment options to patients faster, while expanding patient choice and upholding rigorous standards of efficacy and safety."

For many patients with PID, IG replacement is the only treatment option to maintain immune protection against infections. While existing IG therapies are effective, many patients continue to experience treatment burden, including frequent or high-volume infusions.

"Patients needing lifelong IG therapy for PID experience a significant burden of care. Improving the administration process can diminish the burden of care by substantively impacting the treatment experience," said Richard L. Wasserman, MD, PhD, allergist/immunologist and principal investigator for TAK-881-3001. "These topline results from TAK-881-3001 are encouraging. They show that a highly concentrated, hyaluronidase-facilitated subcutaneous IG can provide immune protection with a more manageable infusion experience intended to enhance the day-to-day lives of patients living with PID."

Analyses from TAK-881-3001 are ongoing, and Takeda anticipates sharing additional results in an upcoming medical forum. Takeda expects to submit applications for TAK-881 to regulatory authorities in the United States, European Union and Japan in fiscal year 2026.

About TAK-881-3001 and TAK-881-3002

TAK-881-3001 was a pivotal Phase 2/3 clinical trial evaluating the pharmacokinetics, efficacy, safety, tolerability and immunogenicity of TAK-881 in adults and pediatric patients aged 2 years and older with Primary Immunodeficiency Disease (PID) who were previously treated with immunoglobulin (IG) therapy. Study participants aged 16 and older were randomized to be treated with TAK-881 followed by HYQVIA or HYQVIA followed by TAK-881 with the same dose and dosing interval of IG for up to 51 weeks in the open label, randomized cross-over study part. Participants aged 2 to < 16 were treated with only TAK-881 for up to 27 weeks in the open label single-arm study part. Further information about the TAK-881-3001 clinical trial is available at ClinicalTrials.gov under study identifier NCT05755035.

TAK-881-3002 is a Phase 3 study evaluating the long-term safety and tolerability of TAK-881 in patients with PID and is the extension study of TAK-881-3001. Further information about the TAK-881-3002 clinical trial is available at ClinicalTrials.gov under study identifier NCT06076642.

About TAK-881

TAK-881 [Immune Globulin Subcutaneous (Human), 20% Solution (SCIG 20%) and Recombinant Human Hyaluronidase] is an investigational liquid medicine comprised of one vial of immunoglobulin (IG) 20% and one vial of Halozyme's recombinant human hyaluronidase (rHuPH20). IG is collected from human plasma and maintains the body's immune system. TAK-881 is infused under the skin into the fatty subcutaneous tissue where the hyaluronidase facilitates the dispersion and increases the absorption of immunoglobulin in the subcutaneous tissue, allowing larger volumes to be infused at a given infusion site. As a SCIG 20% facilitated with hyaluronidase, TAK-881 is being developed with the goal of reducing infusion volume and duration while providing effective immune protection for patients with PID.

About Primary Immunodeficiency Disease (PID)

Primary Immunodeficiency Disease (PID) 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.¹ These conditions result from genetic mutations, which are usually inherited.² The symptoms of PID vary and can include frequent and/or persistent infections and unusual autoimmunity, often leading to prolonged periods of misdiagnosis despite consultations with multiple specialists.³ In the United States, PID affects about 1 in 1,200 people.⁴

About HYQVIA®

HYQVIA® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] is a liquid medicine containing immunoglobulin (IG) 10% and Halozyme's recombinant human hyaluronidase (rHuPH20). HYQVIA is approved by the European Medicines Agency (EMA) as a replacement therapy in adults, children and adolescents (0-18 years) with Primary Immunodeficiency Disease (PID) with impaired antibody protection and with Secondary Immunodeficiency Disease (SID) in patients 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. In addition, it is approved by the EMA in adults, children and adolescents (0-18 years) with chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy after stabilization with intravenous IG therapy (IVIG).

In the United States HYQVIA is approved to treat adults and children two years of age and older with PID as a well as a maintenance therapy for adult patients with CIDP.

HYQVIA is infused under the skin into the fatty subcutaneous tissue and contains IG collected from human plasma. IGs are antibodies that maintain the body's immune system. The hyaluronidase part of HYQVIA facilitates the dispersion and absorption of IG in the subcutaneous space between the skin and the muscle. HYQVIA is infused up to once a month (every two, three or four weeks for CIDP; every three or four weeks for PID).

HyQvia® (Human normal immunoglobulin) 100 mg/ml solution for infusion for subcutaneous use

Important Safety Information (European Union)

Please consult the HyQvia (Human normal immunoglobulin (SCIg)) Summary of Product Characteristics (SmPC) before prescribing, particularly in relation to dosing and treatment monitoring.

GUIDANCE FOR USE: Therapy should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency/CIDP. The medicinal product should be administered via the subcutaneous (SC) route. The dose and dose regimens are dependent on the indication. The dose may need to be individualized for each patient dependent on the PK and clinical response. Dose based on bodyweight may require adjustment in underweight or overweight patients.

CONTRAINDICATIONS: Not be given intravenously or intramuscularly. Hypersensitivity to the active substance or to any of the excipients. Hypersensitivity to human immunoglobulins, especially in very rare cases of IgA deficiency when the patient has antibodies against IgA. Systemic hypersensitivity to hyaluronidase or rHuPH20.

SPECIAL POPULATIONS: Paediatric population: The dosing schedule for children and adolescents (0 to 18 years) for replacement and immunomodulatory therapies is the same as for adults. The warnings and precautions listed in the SmPC apply both to adults and children. Pregnancy: the safety of this medicinal product for use in human pregnancy has not been established in controlled clinical studies and therefore should only be given with caution to pregnant women and breast-feeding mothers. Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected. Fertility: there are currently no clinical safety data available. Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE: Traceability: in order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Precautions for use: if HyQvia is accidentally administered into a blood vessel, patients could develop shock; Certain adverse reactions may occur more frequently in patients who receive human normal immunoglobulin for the first time or, in rare cases, when the human normal immunoglobulin product is switched or when there has been a long interval since the previous infusion; potential complications can often be avoided by initially infusing the product slowly and ensuring that patients are carefully monitored. All other patients should be observed for at least 20 minutes after the administration. When treatment is given at home, support from another responsible person should be available. Patients on self-home treatment and/or their guardian should also be trained to detect early signs of hypersensitivity. In case of adverse reaction, either the rate of administration must be reduced, or the infusion stopped. No chronic changes in the skin were observed in the clinical studies. Patients should be reminded to report any chronic inflammation, nodules or inflammation that occurs at the infusion site and lasts more than a few days. Hypersensitivity to IG 10%: Patients with anti-IgA antibodies, in whom treatment with SCIg products remains the only option, should be treated with HyQvia only under close medical supervision. Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who had tolerated previous treatment with human normal immunoglobulin, please read the SmPC for more information. Hypersensitivity to rHuPH20: any suspicion of allergic or anaphylactic like reactions following rHuPH20 administration requires immediate discontinuation of the infusion and standard medical treatment should be administered, if necessary. Immunogenicity of rHuPH20: development of non-neutralizing antibodies and neutralizing antibodies to the rHuPH20 component has been reported in patients receiving HyQvia in clinical studies. Arterial and venous thromboembolic events have been associated with the use of immunoglobulins. Patients should be sufficiently hydrated before using immunoglobulins. Caution should be exercised in patients with pre-existing risk factors for thromboembolic events. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Thrombosis may also occur in the absence of known risk factors. Patients should be informed about first symptoms of thromboembolic events and be advised to contact their physician immediately upon onset of symptom. Haemolytic anaemia: immunoglobulin products contain antibodies to blood groups (e.g. A, B, D) which may act as haemolysins. Immunoglobulin product recipients should be monitored for clinical signs and symptoms of haemolysis. Aseptic meningitis syndrome (AMS): it has been reported to occur in association with IVIg and SCIg treatment; the symptoms usually begin within several hours to 2 days following immunoglobulin treatment. Patients should be informed about the first symptoms. Discontinuation of immunoglobulin treatment may result in remission of AMS within several days without sequelae. AMS may occur more frequently in association with high-dose (2 g/kg) IVIg treatment. From post-marketing data no clear correlation of AMS to higher doses was observed. Higher incidences of AMS were seen in women. Interference with serological testing: After infusion of immunoglobulins, the transitory rise of the various passively transferred antibodies in the patient's blood may result in misleading positive results in serological testing. Infusions of immunoglobulin products may lead to false positive readings in assays that depend on detection of β-D-glucans for diagnosis of fungal infections. Transmissible agents: standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens. The measures taken are considered effective for enveloped and for the non-enveloped viruses.

INTERACTIONS: Live attenuated virus vaccines Immunoglobulin administration may impair for a period of at least 6-weeks and up to 3-months the efficacy of live attenuated virus vaccines. After administration of this medicinal product, an interval of 3-months should elapse before vaccination with live attenuated virus vaccines. In the case of measles, this impairment may persist for up to 1 year. Therefore, patients receiving measles vaccine should have their antibody status checked.

UNDESIRABLE EFFECTS: The most frequently reported adverse reactions (Ars) were local reactions. The most frequently reported systemic Ars were headache, fatigue, nausea, and pyrexia. The majority of these Ars were mild to moderate. Cases of transient aseptic meningitis, transient haemolytic reactions, increase in serum creatinine level and/or acute renal failure have been observed with human normal immunoglobulin. ADRs frequency per infusion: very common (≥ 1/10): Local reactions (Total, see SmPC for the detailed list of local reactions); common (≥ 1/100 to < 1/10): Headache, Nausea, Abdominal pain, Abdominal pain lower, Abdominal pain upper and Abdominal tenderness, Erythema, Asthenia, Fatigue, Lethargy and Malaise; uncommon (≥ 1/1 000 to < 1/100): Dizziness, Migraine, Tremor, Paraesthesia, Sinus tachycardia and Tachycardia, Blood pressure increased and Hypertension, Diarrhoea, Vomiting, Abdominal distension, Pruritus, Rash, Rash erythematous, Rash macular, Rash maculo-papular and Rash papula, Urticaria, Myalgia, Arthralgia, Limb discomfort and Pain in extremity Back pain, Joint stiffness, Musculoskeletal chest pain, Chills, Oedema, Oedema peripheral and Swelling (systemic), Localised oedema, Peripheral swelling and Skin oedema, Gravitational oedema, Oedema genital, Scrotal swelling and Vulvovaginal swelling, Burning sensation; rare (≥ 1/10 000 to < 1/1 000): Cerebrovascular accident and Ischaemic stroke, Hypotension, Dyspnoea, Groin pain, Haemosiderinuria, Hyperhidrosis, Coombs direct test positive and Coombs test positive.

For EU SmPC, please visit: https://www.ema.europa.eu/en/documents/product-information/hyqvia-epar-product-information_en.pdf

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

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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