Hyaluronidase Recombinant Human

VYVDURA ® now approved for at-home self-injection in Japan for both generalized myasthenia gravis and CIDP argenx’s VYVGART ® and VYVDURA portfolio approved in Japan for three indications – first country globally with access across three indications AMSTERDAM, The Netherlands I December 27, 2024 I argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, today announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) approved VYVDURA for adults with chronic inflammatory demyelinating polyneuropathy (CIDP). VYVDURA is approved for CIDP as a once weekly 30-to-90 second subcutaneous injection, which can be self-administered at home, and is the first and only neonatal Fc receptor (FcRn) blocker approved for the treatment of CIDP. “CIDP is a rare and debilitating disease for which there has been little innovation in treatment in 30 years,” said Luc Truyen, M.D., Ph.D., Chief Medical Officer of argenx. “With VYVDURA, CIDP patients in Japan now have access to a novel therapy with a focused mode of action offering a convenient 30-to-90 second at-home self-injection option with an established efficacy and safety profile, as demonstrated by the ADHERE trial and real-world evidence. By extending the reach of this transformational therapy to thousands more patients, argenx continues to bring efgartigimod, our first-in-class FcRn blocker, to more patients in Japan and around the world suffering from severe autoimmune disease.” CIDP is a progressive, immune-mediated rare and debilitating neuromuscular disorder of the peripheral nervous system. Patients experience a range of disabling mobility and sensory issues, including trouble standing from a seated position, pain and fatigue, and frequent tripping or falling. Many patients become wheelchair bound and are unable to work as the disease progresses. Currently, 85% of patients require ongoing treatment and nearly 88% of treated patients experience residual impairment and disability. The MHLW approval is based on the ADHERE Study, the largest clinical trial to date studying CIDP. In the ADHERE study, 69% (221/322) of patients treated with VYVDURA, regardless of prior treatment, demonstrated evidence of clinical improvement, including improvements in mobility, function and strength. ADHERE met its primary endpoint (p<0.0001) demonstrating a 61% reduction (HR: 0.39 95% CI: 0.25; 0.61) in the risk of relapse versus placebo. Ninety-nine percent of trial participants elected to participate in the ADHERE+ open-label extension. The safety results were generally consistent with the known safety profile of VYVDURA in previous clinical studies and real-world use. VYVDURA was approved by the MHLW for manufacturing and marketing in January 2024 and launched in April 2024 for the treatment of generalized myasthenia gravis (gMG). In March 2024, VYVDURA was designated as an Orphan Drug for the treatment of CIDP by the MHLW. See FDA-approved Important Safety Information below and full Prescribing Information for VYVDURA, which is marketed as VYVGART Hytrulo in the United States, for additional information. What is VYVGART® HYTRULO (efgartigimod alfa and hyaluronidase-qvfc)? VYVGART HYTRULO is a prescription medicine used for the treatment of adult patients with chronic inflammatory demyelinating polyneuropathy (CIDP). IMPORTANT SAFETY INFORMATION Do not use VYVGART HYTRULO if you have a serious allergy to efgartigimod alfa, hyaluronidase, or any of the other ingredients in VYVGART HYTRULO. VYVGART HYTRULO can cause serious allergic reactions and a decrease in blood pressure leading to fainting. VYVGART HYTRULO may cause serious side effects, including: Tell your doctor if you have signs or symptoms of an infection, allergic reaction, or infusion-related reaction. These can happen while you are receiving your VYVGART HYTRULO treatment or afterward. Your doctor may need to pause or stop your treatment. Contact your doctor immediately if you have signs or symptoms of a serious allergic reaction. Before taking VYVGART HYTRULO, tell your doctor if you: What are the common side effects of VYVGART HYTRULO? The most common side effects in efgartigimod-alfa-fcab-treated patients were respiratory tract infection, headache, and urinary tract infection. Additional common side effects with VYVGART HYTRULO are injection site reactions, including rash, redness of the skin, itching sensation, bruising, pain, and hives. These are not all the possible side effects of VYVGART HYTRULO. Call your doctor for medical advice about side effects. You may report side effects to the US Food and Drug Administration at 1-800-FDA-1088. Please see the full Prescribing Information for VYVGART HYTRULO and talk to your doctor. About ADHERE Trial Design The ADHERE trial was a multicenter, randomized, double-blind, placebo-controlled trial evaluating VYVDURA® (efgartigimod alfa and hyaluronidase-qvfc) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP). ADHERE enrolled 322 adult patients with CIDP who were treatment naïve (not on active treatment within the past six months or newly diagnosed) or being treated with immunoglobulin therapy or corticosteroids. The trial consisted of an open-label Stage A followed by a randomized, placebo-controlled Stage B. In order to be eligible for the trial, the diagnosis of CIDP was confirmed by an independent panel of experts. Patients entered a run-in stage, where any ongoing CIDP treatment was stopped and in order to be eligible for Stage A had to demonstrate active disease, with clinically meaningful worsening on at least one CIDP clinical assessment tool, including INCAT, I-RODS, or mean grip strength. Treatment naïve patients were able to skip the run-in period with proof of recent worsening. To advance to Stage B, patients needed to demonstrate evidence of clinical improvement (ECI) with VYVDURA. ECI was achieved through improvement of the INCAT score, or improvement on I-RODS or mean grip strength if those scales had demonstrated worsening during the run-in period. In Stage B, patients were randomized to either VYVDURA or placebo for up to 48 weeks. The primary endpoint was measured once 88 total relapses or events were achieved in Stage B and was based on the hazard ratio for the time to first adjusted INCAT deterioration (i.e. relapse). After Stage B, all patients had the option to roll-over to an open-label extension study to receive VYVDURA. About VYVDURA VYVDURA is a subcutaneous combination of efgartigimod alfa, a human IgG1 antibody fragment marketed for intravenous use as VYVGART, and recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology to facilitate subcutaneous injection delivery of biologics. In binding to the neonatal Fc receptor (FcRn), VYVDURA results in the reduction of circulating IgG. It is the first-and-only approved FcRn blocker administered by subcutaneous injection for the treatment of CIDP. VYVDURA is the proprietary name in Japan for subcutaneous efgartigimod alfa and recombinant human hyaluronidase PH20. It is marketed under different proprietary names in other regions. About Chronic Inflammatory Demyelinating Polyneuropathy Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and serious autoimmune disease of the peripheral nervous system. Although confirmation of disease pathophysiology is still emerging, there is increasing evidence that IgG antibodies play a key role in the damage to the peripheral nerves. People with CIDP experience fatigue, muscle weakness and a loss of feeling in their arms and legs that can get worse over time or may come and go. These symptoms can significantly impair a person’s ability to function in their daily lives. Without treatment, one-third of people living with CIDP will need a wheelchair. About argenx argenx is a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx aims to translate immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first approved neonatal Fc receptor (FcRn) blocker in the U.S., Japan, Israel, the EU, the UK, Canada and China. The Company is evaluating efgartigimod in multiple serious autoimmune diseases and advancing several earlier stage experimental medicines within its therapeutic franchises. For more information, visit www.argenx.com and follow us on LinkedIn, Twitter, and Instagram. SOURCE: argenx

OSAKA, Japan & CAMBRIDGE, Mass.--( BUSINESS WIRE )--Takeda (TSE:4502/NYSE:TAK) today announced that the Japanese Ministry of Health, Labour and Welfare has approved the use of HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] in patients with agammaglobulinemia or hypogammaglobulinemia 1 , disorders characterized by very low or absent levels of antibodies and an increased risk of serious recurring infection caused by primary immunodeficiency (PID) or secondary immunodeficiency (SID) 2 . The approval marks availability of the first and only facilitated subcutaneous immunoglobulin (fSCIG) therapy as a treatment option for appropriate patients in Japan. HYQVIA is the first plasma-derived therapy for subcutaneous injection in Japan that consists of a combination of one vial of Immunoglobulin 10% and one vial of Recombinant Human Hyaluronidase PH20 (rHuPH20). The administration of rHuPH20 increases the dispersion and absorption of immunoglobulin (IG) in the subcutaneous tissue, allowing larger volumes to be infused in the infusion site. This allows for less frequent dosing compared to other subcutaneous IG products, while avoiding the need for venous access. The ability to infuse a larger infusion volume is expected to increase administration flexibility for patients with agammaglobulinemia or hypogammaglobulinemia by decreasing the dosing frequency to once every 3 or 4 weeks, as compared to weekly or bi-weekly with conventional SCIG treatments. The approval is based on data from two pivotal Phase 3, open-label, non-controlled studies evaluating the efficacy, safety, tolerability and pharmacokinetics in Japanese subjects with PID ( NCT05150340 , NCT05513586 ). In these studies, the efficacy and safety profile of HYQVIA in 16 patients aged 2 years or older in Japan were evaluated based on the results of the clinical trials. The Geo Mean of IgG trough level at the last 3 visits was 9.494g/L and was maintained at level comparable to treatment with intravenous or subcutaneous immunoglobulin (Geo Mean of IgG trough level 9.624g/L). The major adverse reactions were pyrexia 5 patients (31.3%) and infusion site erythema, injection site erythema, infusion site swelling, infusion site pain, and headache (12.5%) 1 . Data from two Phase 3 clinical trials conducted in patients with PID in North America ( NCT00814320 , NCT01175213 ) was also included in the submission. “ We are delighted that HYQVIA, approved in more than 40 countries worldwide, has now been approved in Japan,” said Naoyoshi Hirota, Regional Head of Research & Development for Takeda’s Plasma-Derived Therapies Business Unit in Japan. “ The subcutaneous IG therapies currently available in Japan for patients with agammaglobulinemia or hypogammaglobulinemia require infusion once every week or every 2 weeks. We are proud to offer Japanese patients the first and only facilitated subcutaneous treatment option that offers a reduced dosing frequency of every 3 or 4 weeks.” “ There is a high unmet need for plasma-derived therapies (PDTs) in patients in Japan, which is anticipated to increase as education and timely diagnosis rates continue to improve,” said Kristina Allikmets, head of research & development for Takeda’s Plasma-Derived Therapies Business Unit. “ The approval of HYQVIA, the first and only facilitated SCIG treatment, is further evidence of Takeda’s commitment to add to the standard of care for patients in Japan. We look forward to continuing to bring new therapeutic options that support and enhance the experience of patients in our home country throughout the next decade.” With this approval, Takeda is now able to offer a range of SCIG therapies to patients based on their individual administrative needs, reflecting the company’s commitment to offer patients in Japan a broader choice of treatment options. It also follows the announcement of a significant investment to build a new manufacturing facility for plasma-derived therapies (PDTs) in Osaka, Japan. HYQVIA is also currently under review in Japan for additional indications. About Agammaglobulinemia or Hypogammaglobulinemia Agammaglobulinemia is an inherited disorder caused by a gene defect that blocks the growth of normal, mature immune cells called B lymphocytes 3 . Hypogammaglobulinemia is a condition in which patients have low levels of antibodies due either to inherited genetic conditions (PID) or secondary effects (SID) – like chemotherapy, certain comorbid disorders, or immunosuppressants 2 . Individuals with any form of antibody deficiency frequently experience recurring and/or severe infections, and immunoglobulin replacement therapy can increase the level of antibodies in the body. About Primary Immunodeficiency and Secondary Immunodeficiency Primary immunodeficiency describes a heterogeneous group of more than 480 rare genetic diseases wherein part of the immune system is missing or not functioning properly 4 . Secondary immunodeficiency is defined as an acquired impairment of the immune response resulting from an underlying condition or factors extrinsic to the immune system. SID may occur as a consequence of malnutrition, metabolic disorders, use of immunosuppressive medications, chronic infections, malignancies, or severe trauma 5 . Due to their impaired immune system, patients with PID and SID may be more susceptible to infection, and it may take longer to recover from it. In patients with antibody deficiency and increased susceptibility and/or persistent infections, substitution with functional antibodies (immunoglobulin replacement therapy) is the standard of care to support the immune system's functioning 5 . About HYQVIA ® HYQVIA is the combination product for subcutaneous injection containing one each vial of Subcutaneous Immunoglobulin 10% (SCIG10%) and Recombinant Human Hyaluronidase PH20 (rHuPH20). As of May 2024, HYQVIA has been approved in more than 40 countries worldwide. HYQVIA Product Overview in Japan Brand Name HYQVIA 10% Subcutaneous Injection Set 5g/50mL 10g/100mL 20g/200mL Generic Name pH4 Treated Acid Human Globulin (Subcutaneous Injection) Vorhyaluronidase Alfa (Genetical Recombination) Indications Agammaglobulinemia or Hypogammaglobulinemia Dosage and Administration Human immunoglobulin G is administered subcutaneously at the same site within approximately 10 minutes after the subcutaneous injection of vorhyaluronidase alfa (genetical recombination). Initiate the treatment with human immunoglobulin G and vorhyaluronidase alfa (genetical recombination) at 1/3 or 1/4 of the doses described below, and then the doses are titrated up. Note that the dosing interval should be extended depending on the doses. •Usually, 150 – 600 mg (1.5 – 6 mL)/kg of body weight of human immunoglobulin G is administered once every 3 weeks or 200 – 800 mg (2 – 8 mL)/kg of body weight of human immunoglobulin G is administered once every 4 weeks. •Vorhyaluronidase alfa (genetical recombination) is administered at the dose of 80 units (0.5 mL) per 1 g of human immunoglobulin G. The dose and the number of doses per 3 or 4 weeks may be adjusted according to the patient’s condition. 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 . Important Notice For the purposes of this notice, “press release” means this document, any oral presentation, any question-and-answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. 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Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. ______________________________ REFERENCES 1 HYQVIA 10% Subcutaneous Injection Set Package Insert in Japan. 2 Pimenta et al. Hypogammaglobulinemia: a diagnosis that must not be overlooked. BJMBR . 2019;52(10): e8926. 3 National Organization for Rare Disorders https://rarediseases.org/rare-diseases/agammaglobulinemia/ 4 Tangye et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol . 2022;42(7):1473-1507. 5 Tuano KS, Seth N, Chinen J. Secondary immunodeficiencies: An overview. Ann Allergy Asthma Immunol . 2021;127(6):617-626.