- Data Show that HYQVIA^® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] Reduced Relapse Rate Versus Placebo in CIDP Patients When Used as a Maintenance Therapy

- Company Continues to Analyze Data with Goal of Submitting Regulatory Applications in the US and EU in FY2022

Takeda (TSE:4502/NYSE:TAK) today announced that ADVANCE-1, a randomized, placebo-controlled, double-blind Phase 3 clinical trial evaluating HYQVIA^® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] for the maintenance treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), met its primary endpoint. Topline data show that HYQVIA reduced relapse of neuromuscular disability and impairment when used as a maintenance therapy for CIDP, supporting its potential as a facilitated subcutaneous immunoglobulin (fSCIG) solution that could allow for monthly infusion for many CIDP patients. Analyses from ADVANCE-1 are ongoing, and the company anticipates disclosing additional data in an upcoming medical forum.

The pivotal ADVANCE-1 clinical trial evaluated the efficacy, safety and tolerability of HYQVIA in 132 adult patients with CIDP who had been on a stable dosing regimen of intravenous immunoglobulin (IVIG) therapy for at least three months prior to infusion. Analysis of the primary endpoint shows that HYQVIA, when administered at the same dose and dosing interval as the patient’s previous IVIG, reduced CIDP relapse as compared to placebo [9.7% vs 31.4%, respectively; p-value = 0.0045], as measured by Inflammatory Neuropathy Cause and Treatment (INCAT). The majority of patients in the study received a four-week dosing regimen of HYQVIA.

“While the efficacy and safety of intravenous immunoglobulin therapy in CIDP is well-established,¹ there is a substantial burden associated with chronic administration of therapies for patients with CIDP,” said Kristina Allikmets, Head of Research & Development for Takeda’s Plasma-Derived Therapies Business Unit. “There is a significant need for a treatment that is both efficacious and can be administered monthly at home or in the hospital with a reduced number of infusion sites and reduced administration duration and frequency. We are committed to bringing this therapy to people with CIDP as quickly as possible.”

Chronic inflammatory demyelinating polyradiculoneuropathy is a rare and chronic autoimmune disease that affects the peripheral nervous system.^2,3 The condition results in progressive symmetric weakness and impaired sensory function in the arms and legs.² Immunoglobulin therapy has become standard of care for CIDP patients due to its broad, multifaceted, anti-inflammatory and immunomodulatory effect.^4,5,6

In topline analyses of ADVANCE-1, HYQVIA showed a favorable safety profile, further supporting its use as a maintenance therapy for CIDP. Of the 62 patients treated with HYQVIA, the majority of treatment-related adverse events were reported as mild or moderate. No new safety risks were reported with HYQVIA. The safety profile of HYQVIA in CIDP will be further supported by data from the ongoing ADVANCE-3 clinical trial, the longest extension study of its kind with up to six years of follow-up data on some participants.⁷

Upon full data analyses, Takeda intends to submit applications for HYQVIA to regulatory authorities in the United States and European Union in fiscal year 2022.

About the ADVANCE Clinical Program

ADVANCE-1 was a Phase 3, multicenter, placebo-controlled, double-blinded study to evaluate the efficacy, safety and tolerability of HYQVIA^® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] as a maintenance therapy to prevent relapse in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The global study included 132 adults with a confirmed diagnosis of CIDP and who had remained on a stable dosing regimen of intravenous immunoglobulin (IVIG) therapy for at least three months prior to screening.

The primary endpoint of the clinical trial was the proportion of subjects who experienced a worsening of functional disability, defined as an increase of ≥1 point relative to the pre-subcutaneous (SC) treatment baseline score in two consecutive adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores. Some of the secondary endpoints included time to relapse, effect on activities of daily living (ADL), safety and tolerability. Patients were randomized to receive either HYQVIA or placebo at the same dose and infusion frequency as their prior IVIG treatment (every two, three or four weeks) for six months or until relapse. Patients who relapsed were offered IVIG treatment with Gammagard Liquid^® (Kiovig^®) for a period of six months as part of the open-label rescue arm of the study (ADVANCE-2). Those who remained relapse free were offered to continue HYQVIA treatment as part of ADVANCE-3, an open-label extension clinical trial to assess the long-term safety, tolerability and immunogenicity of HYQVIA in participants with CIDP who completed ADVANCE-1.

Further information about the ADVANCE-1 clinical trial is available at ClinicalTrials.gov under study identifier NCT02549170.

About Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic, acquired, immune-mediated condition affecting the peripheral nervous system that is characterized by progressive, symmetric weakness in distal and proximal limbs and impaired sensory function in extremities.² A rare, debilitating and slowly progressing or relapsing disease,⁸ CIDP has a prevalence of about 0.67-10.3 cases per 100,000 globally.⁹ The primary symptoms of CIDP are slowly progressive, contributing to delays in accurate diagnosis from months to years.^2,10

About HYQVIA^®

HYQVIA^® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] is a liquid medicine containing Recombinant Human Hyaluronidase and immunoglobulins (Ig) and approved in the United States to treat adult patients 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). For more information on HYQVIA visit HyQvia.com.

U.S. Indication and Limitation of Use

HYQVIA is indicated for the treatment of primary immunodeficiency (PI) in adults. 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.

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: May 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.
• 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 and may occur more frequently in females. 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 Interactions

The most common adverse reactions observed in >5% of patients in the clinical trials were: local adverse reactions including pain, erythema, edema, and pruritis, 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).

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

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

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). 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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Medical information

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⁷ Takeda data on file.

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