Bruton Type Agammaglobulinemia

Seattle Children's Research Institute will be one of Genezen's first customers to leverage its cutting-edge Cytegrity™ technology from biotech leader CSL for stable and scalable high-titer lentivirus production. FISHERS, Ind., March 6, 2024 /PRNewswire/ -- Seattle Children's Research Institute, the research division of Seattle Children's Hospital and renowned global leader in pediatric research, and Genezen, a leading gene and cell therapy contract development and manufacturing organization, have unveiled a strategic manufacturing partnership for Seattle Children's Research Institute's X-linked agammaglobulinemia (XLA) program. This collaborative effort is focused on leveraging Genezen's viral vector process development and cGMP manufacturing expertise to advance Seattle Children's XLA gene therapy program. XLA is a rare primary immunodeficiency condition characterized by abnormally low levels of immunoglobulins, also referred to as antibodies. XLA is an X-chromosome-linked inherited disorder that affects males and is caused by defects in the BTK gene required for B cell generation and function. The inability to produce B cells or the immunoglobulins (antibodies) reduces the body's ability to fight infection. Infants with XLA may initially appear healthy as they are protected by maternal antibodies during their early months. However, as these maternal antibodies wane, these infants often begin to grapple with severe, recurring bacterial infections affecting various parts of their body, including the ears, lungs, sinuses, and skin, which can pose life-threatening risks. No cure presently exists for XLA. The primary objective of XLA gene therapy is to genetically modify stem cells from the bone marrow to permit the generation of new B cells and antibody-producing B cells to restore antibody production and bolster the immune system. Steve Favaloro, Chief Executive Officer of Genezen, commented on the partnership: "I am extremely excited for our team to support the world-class researchers at Seattle Children's Research Institute as they progress their XLA gene therapy into the clinic. With this program, Seattle Children's is one of our first customers to leverage our Cytegrity™ producer cell line offering from CSL. The Genezen team is dedicated to a science-first, service-focused approach for our innovator clients – I know our team will add tremendous value to Seattle Children's Hospital and XLA patients." Furthermore, David J. Rawlings, MD, the Director of the Center for Immunity and Immunotherapies and Division Chief of Immunology at Seattle Children's, as well as a professor of pediatrics and immunology at the University of Washington School of Medicine, added his perspective: "Our team has developed a novel lentiviral platform for XLA gene therapy that is safe and effective in extensive animal and human cell pre-clinical studies. As we move forward to treat XLA patients, we are excited to work with Genezen to generate the high-quality clinical vector required for this important program." About Genezen Genezen is a contract development and manufacturing organization (CDMO) with a decade's experience at the heart of the rapid growth in the gene and cell therapy market. Genezen is a leader in the supply of retroviral vectors, lentiviral vectors, and AAV. Led by an extremely experienced team, a science-first approach influences continual investment in scalable, high-yield manufacturing processes and best-in-class technologies. For more information about Genezen, please visit genezen.com. Media Contact Connor Halverson That's Nice LLC Tel: +1 212-366-4455 Email: connor@thatsnice.com SOURCE Genezen

OSAKA, Japan & CAMBRIDGE, MA, USA I January 29, 2024 I Takeda ( TSE:4502/NYSE:TAK ) today announced that the U.S. Food and Drug Administration (FDA) has approved GAMMAGARD LIQUID ® [Immune Globulin Infusion (Human) 10% solution] as an intravenous immunoglobulin (IVIG) therapy to improve neuromuscular disability and impairment in adults with chronic inflammatory demyelinating polyneuropathy (CIDP). 1 It can be used as induction therapy, which includes an induction dose followed by maintenance doses. 1 For treatment of CIDP, GAMMAGARD LIQUID has not been studied in immunoglobulin-naive patients nor as maintenance therapy for periods longer than six months. 1 This milestone follows the recent FDA approval of HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] for maintenance therapy to prevent the relapse of neuromuscular disability and impairment in adults with CIDP. 2 HYQVIA is the only combination of immunoglobulin (IG) and hyaluronidase, which makes it a facilitated subcutaneous IG infusion. 2 “The approval of GAMMAGARD LIQUID for treatment of CIDP is an encouraging validation of our decades-long commitment to advancing plasma-derived therapies on behalf of people living with rare neuromuscular disorders and bringing our portfolio of differentiated IG therapies to these patients,” said Richard Ascroft, senior vice president and head of Takeda’s U.S. Plasma-Derived Therapies Business Unit. “Together with the recent HYQVIA approval in the U.S., we can now offer induction and maintenance therapy options to adults living with CIDP that may accommodate their personal treatment needs.” The approval is based on results from a prospective, open-label, single-arm, multicenter clinical study (ADVANCE-CIDP 2) that evaluated the efficacy and safety of GAMMAGARD LIQUID in adults with CIDP who developed a relapse in the randomized, double-blinded, placebo-controlled study evaluating efficacy, safety and tolerability of HYQVIA (ADVANCE-CIDP 1) in adults with CIDP. Efficacy in ADVANCE-CIDP 2 was based on responder rate, where a responder was defined as a subject who demonstrated an improvement of functional disability. The responder rate was 94.4% (N=18, 95% CI: 74.2% to 99.0%). Improvement in grip strength and change in Rasch-built Overall Disability Scale (R-ODS) score were recorded across participants. 1 The most common adverse reactions observed in ≥5% of clinical study patients were headache, pyrexia, anemia, leukopenia, neutropenia, illness, blood creatinine increased, dizziness, migraine, somnolence, tremor, nasal dryness, abdominal pain upper, vomiting, chills, nasopharyngitis and pain in extremity. 1 CIDP is a rare, acquired, immune-mediated neuromuscular disorder affecting the peripheral nervous system. 3,4 It is characterized by progressive, symmetric symptoms such as weakness, tingling or loss of feeling in distal and proximal limbs, loss of reflexes and difficulty walking. 3 Because its symptoms may overlap with other rare, neuromuscular conditions, CIDP may be misdiagnosed. 5 The mechanism of action of immunoglobulins in the treatment of CIDP in adults has not been fully elucidated but may include immunomodulatory effects. 1 “As the standard of care for the treatment of CIDP, IG therapy is thought to help normalize compromised immune systems through immunomodulatory mechanisms,” said Dr. Mamatha Pasnoor, professor in the Department of Neurology at the University of Kansas Medical Center. “Because CIDP is a progressive and complex disease, multiple treatment options are needed, and clinicians now have an additional therapy that can help adults with CIDP manage their disease.” GAMMAGARD LIQUID is the only IVIG with multiple neuromuscular disorder indications in the U.S. since it is now approved for CIDP and it is the only FDA-approved IVIG to treat multifocal motor neuropathy as a maintenance therapy to improve muscle strength and disability in adults. 1 It is also indicated in the U.S. as a replacement therapy for people two years of age or older living with primary immunodeficiency. 1 About GAMMAGARD LIQUID GAMMAGARD LIQUID ® [Immune Globulin Infusion (Human) 10% solution] is an intravenous immunoglobulin (IVIG) that is infused into the veins. GAMMAGARD LIQUID is approved in the U.S. as an IG therapy to improve neuromuscular disability and impairment in adult patients with CIDP, as a replacement therapy for primary immunodeficiency (PI) in adult and pediatric patients two years of age and older, and as a maintenance therapy to improve muscle strength and disability in adult patients with multifocal motor neuropathy (MMN). Also known as KIOVIG outside the U.S. and Canada, it is approved in 66 countries worldwide. About HYQVIA HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] is a liquid medicine containing Recombinant Human Hyaluronidase and immunoglobulin (IG) and is approved in the U.S. to treat adults and children two years of age and older with primary immunodeficiency (PI), and as maintenance therapy to prevent relapse of neuromuscular disability and impairment in adult patients with CIDP. It is also approved by the European Medicines Agency (EMA) 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 IG collected from human plasma. IG 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 PI). About ADVANCE-CIDP 2 ADVANCE-CIDP 2 was a prospective, open-label, single-arm, multicenter clinical study that evaluated the efficacy and safety of GAMMAGARD LIQUID in adults with CIDP who developed a relapse in the randomized, double-blinded, placebo-controlled study evaluating efficacy, safety and tolerability of HYQVIA (ADVANCE-CIDP 1) in adults with CIDP. The 18 patients who relapsed during ADVANCE-CIDP 1 were offered enrollment in ADVANCE-CIDP 2. GAMMAGARD LIQUID was administered at an induction dose of 2 g/kg body weight, followed by maintenance infusions at every three weeks for a period of six months. The dose of GAMMAGARD LIQUID treatment could be adjusted at the investigator's discretion. Adjustments to the dosing interval of every three weeks were not allowed. All subjects completed the study. All dosed subjects were analyzed for efficacy and safety. Efficacy of ADVANCE-CIDP 2 was based on responder rate, where a responder is defined as subjects who had at least a one-point decrease in the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score at the completion of the treatment period (six months). The responder rate was 94.4% (N=18, 95% CI: 74.2% to 99.0%). The INCAT score returned to baseline values prior to joining the study in 17 of the 18 subjects (94.4%) at six months. All subjects had improvement in functional ability as defined by a composite outcome metrics that included INCAT score, grip strength, or Rasch-built Overall Disability Scale (R-ODS) score. Further information about the ADVANCE-CIDP 2 study is available at ClinicalTrials.gov under study identifier NCT02549170 . INDICATIONS GAMMAGARD LIQUID is indicated as replacement therapy for Primary Humoral Immunodeficiency (PI) in adult and pediatric patients ≥2 years, as a maintenance therapy to improve muscle strength and disability in adult patients with Multifocal Motor Neuropathy (MMN), and as a therapy to improve neuromuscular disability and impairment in adult patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). LIMITATIONS OF USE (CIDP): GAMMAGARD LIQUID has not been studied in immunoglobulin-naive patients with CIDP. GAMMAGARD LIQUID maintenance therapy in CIDP has not been studied for periods longer than 6 months. After responding during an initial treatment period, not all patients require indefinite maintenance therapy with GAMMAGARD LIQUID in order to remain free of CIDP symptoms. Individualize the duration of any treatment beyond 6 months based upon the patient’s response and demonstrated need for continued therapy. HYQVIA is indicated for the treatment of Primary Immunodeficiency (PI) in adults and pediatric patients two years of age and older and for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment in adults. HYQVIA is for subcutaneous use only. GAMMAGARD LIQUID for PI is for intravenous or subcutaneous use. GAMMAGARD LIQUID for MMN and CIDP is for intravenous use only. IMPORTANT SAFETY INFORMATION WARNING: THROMBOSIS HYQVIA and GAMMAGARD LIQUID WARNING: RENAL DYSFUNCTION and ACUTE RENAL FAILURE GAMMAGARD LIQUID Contraindications 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. 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 dysfunction/failure has been reported in association with infusions of GAMMAGARD LIQUID . 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. 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. Aseptic Meningitis Syndrome: Has been reported with use of IG, including HYQVIA 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. The syndrome usually begins within several hours to two days following IG treatment. Hemolysis: HYQVIA and GAMMAGARD LIQUID 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 HYQVIA and GAMMAGARD LIQUID 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 of variant Creutzfeldt-Jakob disease (vCJD) have been associated with GAMMAGARD LIQUID , and no cases 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. Additional Warnings and Precautions for HYQVIA 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. Spread of Localized Infection: Do not infuse HYQVIA into or around an infected area due to potential risk of spreading a localized infection. Additional Warnings and Precautions for GAMMAGARD LIQUID Hyperproteinemia, increased serum viscosity, and hyponatremia may occur. It is critical to distinguish true hyponatremia from a pseudohyponatremia because certain treatments may lead to volume depletion, a further increase in serum viscosity, and a predisposition to thromboembolic events. Adverse Reactions HYQVIA The most common adverse reactions observed in >5% of patients in the clinical trials were: PI: 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. CIDP: local reactions, headache, pyrexia, nausea, fatigue, erythema, pruritus, increased lipase, abdominal pain, back pain, and pain in extremity. GAMMAGARD LIQUID The most serious adverse reactions observed in clinical studies in PI was aseptic meningitis, and in MMN were pulmonary embolism and blurred vision. The most common adverse reactions observed in ≥5% of patients in the clinical trials were: IV administration for PI: 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 for PI: 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. IV administration for MMN: Headache, chest discomfort, muscle spasms, muscular weakness, nausea, oropharyngeal pain, and pain in extremity. IV administration for CIDP: Headache, pyrexia, anemia, leukopenia, neutropenia, illness, blood creatinine increased, dizziness, migraine, somnolence, tremor, nasal dryness, abdominal pain upper, vomiting, chills, nasopharyngitis, and pain in extremity. 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 for GAMMAGARD LIQUID, please visit: https://www.shirecontent.com/PI/PDFs/GAMLIQUID_USA_ENG.pdf For Full U.S. Prescribing Information for HYQVIA, 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 . 1 GAMMAGARD LIQUID ® [Immune Globulin Infusion (Human) 10% solution] U.S. Prescribing Information. https://www.shirecontent.com/PI/PDFs/GAMLIQUID_USA_ENG.pdf 2 HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] U.S. Prescribing Information. https://www.shirecontent.com/PI/PDFs/HYQVIA_USA_ENG.pdf 3 Dalakas MC. Nat Rev Neurol . 2011;7(9):507–17. 4 GBS CIDP Foundation International. Voice of the Patient Report. August 26, 2022. www.gbs-cidp.org . Accessed August 2022. 5 Broers MC, Bunschoten C, Nieboer D, Lingsma HF, Jacobs BC. Eur J Neurol . 2021;28(6):2065-2073. SOURCE: Takeda Pharmaceutical Co

Eli Lilly’s Jaypirca. Eli Lilly’s attempt to wrestle a leukemia market from companies including AbbVie, AstraZeneca, BeiGene and Johnson & Johnson has analysts purring, with the GlobalData team tipping the drugmaker to capture 60% of demand and deliver $3 billion in annual sales. The GlobalData report covers the use of BTK inhibitors in the treatment of chronic lymphocytic leukemia (CLL). Pharmacyclics, now part of AbbVie, and J&J created the market with Imbruvica but now face a sea of threats, with the Inflation Reduction Act, increased competition and the looming prospect of generics pointing to a downward trajectory.   AstraZeneca’s Calquence began challenging Imbruvica for the CLL market in 2019 and BeiGene’s Brukinsa joined the party last year. But the GlobalData analysts expect Lilly to come from behind to become the dominant force in CLL in the coming years. Lilly won accelerated FDA approval for Jaypirca in CLL last month. While the drugmaker, which acquired Jaypirca in its $8 billion takeover of Loxo Oncology, has ceded a headstart to rivals, it has a differentiated asset that the GlobalData analysts believe will translate into leadership of the blockbuster market.  The other molecules bind covalently to BTK and are susceptible to resistance mutations. Jaypirca binds noncovalently and triggers responses in patients who have progressed on other BTK inhibitors, as well as in people without mutations that confer drug resistance. GlobalData’s team predicts Jaypirca will capture 60% of the CLL market by 2032, leaving Calquence and Brukinsa in the dust. Calquence and Brukinsa are forecast to come in second and third with 21.7% and 15.8% of the market, respectively. By then, the loss of market exclusivity is forecast to have eaten away at Imbruvica sales. The GlobalData report also mentions Velexbru, an Ono Pharmaceutical product that Gilead struck a deal for in 2014, but makes no reference to Merck & Co.’s noncovalent BTK inhibitor nemtabrutinib. Merck acquired the candidate in its $2.7 billion takeover of ArQule a few years ago and is on course to wrap up a phase 3 trial in CLL in 2027.