FGF23

BridgeBio Pharma announced it has granted Kyowa Kirin exclusive rights in Japan to develop and sell infigratinib for achondroplasia and related bone growth disorders. As part of the deal announced Wednesday, Kyowa Kirin will pay BridgeBio $100 million upfront plus unspecified milestones, along with up to high-20s percent royalties on potential future sales.Infigratinib is a selective oral ATP-competitive inhibitor of fibroblast growth factor receptors designed to target FGFR3-driven skeletal dysplasias such as achondroplasia and hypochondroplasia at their source. In December, BridgeBio dosed the first patient in the Phase III PROPEL 3 trial evaluating infigratinib in children with achondroplasia after a mid-stage study showed that it significantly increased annual height velocity by an average +3.38 cm/year through to six months.Providing a "once-daily oral treatment option" is a key goal for the programme based on patient community needs, according to Justin To, chief executive of QED Therapeutics, BridgeBio’s skeletal dysplasia-focused subsidiary. Japanese trial in 2025Kyowa Kirin aims to begin a pivotal trial in Japan next year for infigratinib, which adds to its portfolio in bone disorders and rare diseases. The Japanese drugmaker previously partnered with Ultragenyx Pharmaceutical to develop injectable Crysvita (burosumab-twza), a monoclonal antibody that blocks FGF23 to treat X-linked hypophosphataemia as well as tumour-induced osteomalacia.If approved, infigratinib could compete against BioMarin Pharmaceutical's once-daily injectable treatment Voxzogo (vosoritide), which Japan’s Ministry of Health, Labor and Welfare greenlight in 2022 to treat achondroplasia in children of all ages, whose growth plates are not closed.  BridgeBio continues deal spreeThe arrangement with Kyowa Kirin adds to the tally of recent deals done by BridgeBio to help fund its burgeoning pipeline of drugs focused on addressing genetically well-defined conditions amid stiff competition.Earlier this year it reached a royalty agreement with Blue Owl and CPP Investments that will see it pocket a $500-million milestone payment if another pipeline drug, acoramidis, scores an approval in the US for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The total financing from the two funds could climb to as much as $1.25 billion. Acoramidis, which is currently under review by the FDA with a decision expected by November 29, is expected to compete against Pfizer's ATTR-CM treatment Vyndamax (tafamidis).

Claims database analyses show increasing prevalence and impact of XLH-related morbidities with age, underscoring life-long burden of disease PRINCETON, N.J., Oct. 16, 2023 /PRNewswire/ -- Kyowa Kirin, Inc., an affiliate of Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company based in Japan, presented two posters at the American Society for Bone and Mineral Research (ASBMR) 2023 annual meeting in Vancouver, BC, Canada, demonstrating the significant burden and progressive, accumulative nature of X-linked hypophosphatemia (XLH), a rare genetic metabolic bone disease. "Because XLH is a progressive, life-long disease, it's important to understand the clinical characteristics and real-world impact on patients over time," said Zhiyi Li, MA, MBA, one of the study authors and director of health economics and outcomes research at Kyowa Kirin North America. "Both studies found that serious disease-related morbidities often start at a young age and accumulate over time, an important consideration for physicians when making decisions about patient care." Real-world characteristics and disease history of patients with X-linked hypophosphatemia treated with burosumab: a United States claims database study In this retrospective cohort study, researchers examined the patient characteristics and disease history of 1,358 people ≥6 months of age prior to initiation of treatment with burosumab using Komodo Health's Healthcare Map™, a real-world de-identified patient-level claims database assembled from clearinghouse, payer, and provider data sources. Among the claims assessed, researchers found high levels of XLH-related morbidities and extra-musculoskeletal manifestations, including osteoarthritis, arthralgia (joint pain), fractures, muscle pain, spinal stenosis, hypertension, obesity, depression, renal disease and enthesopathy, a disorder that affects the site of attachment between bones and tendons or ligaments.1 Most of these complications were seen in early adulthood and increased with age group. Most patients had received some form of conventional therapy for XLH prior to burosumab treatment, with 61% receiving calcitriol and 43% receiving phosphate supplements. Physical therapy use was also observed across all age groups. There were several study limitations including the lack of a specific diagnosis code for XLH. Patients were identified using diagnosis codes for familial hypophosphatemia (FH) and other disorders of phosphorus metabolism; however, the inclusion of burosumab claims helped to minimize the inclusion of misdiagnosed patients, as XLH is the only disorder of FH for which burosumab is indicated. In addition, the study used non-primary insurer (open source) claims, which captures a higher number of medical claims as compared to payer-complete (closed source) claims; however, completeness is not guaranteed. Older patients were under-represented in the study population, limiting the generalizability of the findings to this group. Clinical and treatment characteristics of pediatric and adult patients with familial hypophosphatemia compared with demographically matched controls In this retrospective observational cohort study, researchers examined healthcare claims data from the Merative™ MarketScan® Commercial and Medicare Databases. The analysis compared 570 patients with at least one diagnosis code for FH to 1,710 people without FH in a matched control group. FH represents a group of rare genetic disorders characterized by impaired renal phosphate conservation; roughly 80% of FH cases are classified as XLH.2 Patients were excluded from the study if ever prescribed burosumab. The study found patients with FH experienced multiple FH-related morbidities, supplemented with oral phosphate and active vitamin D, and used healthcare services for managing orthopedic conditions at a significantly greater rate than the control group. The differences between the study groups were apparent even among young children and persisted throughout a person's life. Key findings included: Kidney disease, joint pain, osteoarthritis, delayed growth/walking, muscle weakness, and fracture were the most common FH-related morbidities; all were significantly more common among patients with FH (P<0.001) and generally increased with age. Depression (FH: 22.5% vs. controls: 5.6%), hypertension (55.4% vs. 17.4%), and obesity (34.0% vs. 16.4%) were more common among patients with FH (P<0.001). Most monitoring and management practices to control FH and associated morbidities were more common among patients with FH, including laboratory tests, physical therapy, and use of walking assistance devices (all P <0.001). This study was limited to patients with commercial health insurance or Medicare coverage; results may not be generalizable to patients with other types of insurance (e.g., Medicaid) or the uninsured, and the study population may under-represent the true burden of disease. Patients with FH who received burosumab during the study period were excluded. The outcomes assessed in this study may differ for burosumab-treated patients. About X-linked hypophosphatemia X-linked hypophosphatemia is a rare, lifelong, genetic disease that can impact the bones and muscles in both children and adults. In individuals with XLH, the body doesn't hold on to enough phosphorus, which is an essential mineral for bone health. This is due to the production of excess fibroblast growth factor 23 (FGF23), causing the body to release too much phosphorus through the urine. When phosphorus levels are too low (hypophosphatemia), it can cause the softening and weakening of growing bones in children (rickets) and mature bones in adults (osteomalacia). In children, XLH typically appears as bowed legs or knock knees. Over time, bone weakening can also lead to bone abnormalities in the legs, delayed growth, and short stature. In adults, XLH may cause osteomalacia, fractures and pseudo-fractures, and hypophosphatemia. About CRYSVITA® (burosumab-twza) Injection CRYSVITA is a recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Kirin, which binds to and inhibits the biological activity of FGF23, the underlying cause of hypophosphatemia in XLH. By blocking FGF23, CRYSVITA helps to restore phosphorus reabsorption in the kidneys and increase the production of active vitamin D, which enhances intestinal absorption of phosphate and calcium. U.S. CRYSVITA Indication CRYSVITA is a fibroblast growth factor (FGF23) blocking antibody indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older. Important Safety Information CONTRAINDICATIONS CRYSVITA is contraindicated: In concomitant use with oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia. When serum phosphorus is within or above the normal range for age. In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism. WARNINGS AND PRECAUTIONS Hypersensitivity Hypersensitivity reactions (e.g., rash, urticaria) have been reported in patients with CRYSVITA. Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment. Hyperphosphatemia and Risk of Nephrocalcinosis Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of nephrocalcinosis. For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on a patient's serum phosphorus levels. Injection Site Reactions Administration of CRYSVITA may result in local injection site reactions. Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment. ADVERSE REACTIONS Pediatric Patients Adverse reactions reported in 10% or more of CRYSVITA-treated pediatric XLH patients across three studies are: pyrexia (55%, 44%, and 62%), injection site reaction (52%, 67%, and 23%), cough (52%), vomiting (41%, 48%, and 46%), pain in extremity (38%, 46%, and 23%), headache (34% and 73%), tooth abscess (34%, 15%, and 23%), dental caries (31%), diarrhea (24%), vitamin D decreased (24%, 37%, and 15%), toothache (23% and 15%), constipation (17%), myalgia (17%), rash (14% and 27%), dizziness (15%), and nausea (10%). Post-marketing experience reported in CRYSVITA-treated pediatric XLH patients: blood phosphorus increased. Adult Patients Adverse reactions reported in more than 5% of CRYSVITA-treated adult XLH patients and in at least 2 patients more than placebo in one study are: back pain (15%), headache (13%), tooth infection (13%), restless legs syndrome (12%), vitamin D decreased (12%), dizziness (10%), constipation (9%), muscle spasms (7%), and blood phosphorus increased (6%). Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. It is unknown if CRYSVITA therapy exacerbates spinal stenosis or spinal cord compression. USE IN SPECIFIC POPULATIONS There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Serum phosphorus levels should be monitored throughout pregnancy. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-844-768-3544. There is no information regarding the presence of CRYSVITA in human milk or the effects of CRYSVITA on milk production or the breastfed infant. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CRYSVITA and any potential adverse effects on the breastfed infant from CRYSVITA or from the underlying maternal condition. PATIENT COUNSELING INFORMATION Advise patients not to use any oral phosphate and/or active vitamin D analog products. Instruct patients to contact their physician if hypersensitivity reactions, injection site reactions, and restless legs syndrome induction or worsening of symptoms occur. You may report side effects to the FDA at (800)FDA-1088 or . You may also report side effects to Kyowa Kirin, Inc. at 1-844-768-3544. For important risk and use information, please see the full Prescribing Information for CRYSVITA. About Kyowa Kirin Kyowa Kirin strives to create and deliver novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company with a more than 70-year heritage, we apply cutting-edge science including expertise in antibody research and engineering, to address the needs of patients and society across multiple therapeutic areas including Nephrology, Oncology, Immunology/Allergy and Neurology. Across our four regions – Japan, Asia Pacific, North America and EMEA/International – we focus on our purpose, to make people smile, and are united by our shared values of commitment to life, teamwork/Wa, innovation, and integrity. You can learn more about the Kyowa Kirin North America at: . References Sudoł-Szopińska I, Kwiatkowska B, Prochorec-Sobieszek M, et al. Enthesopathies and enthesitis. part 1. J Ultrason. 2015;15(60):72-84. Jagtap VS, Sarathi V, Lila AR, et al. Hypophosphatemic rickets. Indian J Endocrinol and Metab. 2012;16(2):177-182. SOURCE Kyowa Kirin

Five poster presentations provide greater understanding of patient profiles and real-world experiences of people living with XLH PRINCETON, N.J., Oct. 12, 2023 /PRNewswire/ -- Kyowa Kirin, Inc., an affiliate of Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company based in Japan, will share new research that advances understanding about the real-world experiences and clinical characteristics of children, adolescents, and adults living with X-linked hypophosphatemia (XLH), a rare genetic metabolic bone disease. The findings will be presented in a series of poster presentations at the American Society for Bone and Mineral Research (ASBMR) 2023 annual meeting, which takes place October 13-16 in Vancouver, BC, Canada. "Individuals living with XLH face a lifelong struggle of managing their disease and progressively worsening morbidities, which negatively impact their life," said Zhiyi Li, MA, MBA, Director of Health Economics and Outcomes Research at Kyowa Kirin North America. "The breadth of the research we are presenting at ASBMR reflects our commitment to helping inform a more complete understanding of XLH and its' management." Kyowa Kirin will present the following posters at the ASBMR annual meeting: "Real-world characteristics and disease history of patients with X-linked hypophosphatemia treated with burosumab: a United States claims database study" (Poster #SAT-493) Lead author: Kathryn Dahir, MD, Vanderbilt University Medical Center Poster Session I; Saturday, October 14, 1:30 – 3:00 pm PDT "Clinical and treatment characteristics of pediatric and adult patients with familial hypophosphatemia compared with demographically matched controls" (Poster #SAT-519) Lead author: Zhiyi Li, MA, MBA, Kyowa Kirin North America Poster Session I; Saturday, October 14, 1:30 – 3:00 pm PDT "Association between work productivity and characteristics of adults with X-linked hypophosphatemia: an analysis of the XLH Disease Monitoring Program" (Poster #SAT-496) Lead author: Aliya Khan, MD, McMaster University Poster Session I; Saturday, October 14, 1:30 – 3:00 pm PDT "Age at diagnosis of XLH amongst children with and without a family history: findings from the International XLH Registry" (Poster #SUN-500) Lead author: Suma Uday, MBBS, FRCPCH, PhD, Birmingham Women's and Children's Hospital (UK) Poster Session II; Sunday, October 15, 1:30 – 3:00 pm PDT "A patient-centered and multi-stakeholder co-designed, mixed method, observational, prospective study protocol: Example of the adolescent experience of treatment for X-linked hypophosphatemia (XLH)" (Poster #SUN-496) Lead author: Vrinda Saraff, MD, Birmingham Women's and Children's Hospital (UK) Poster Session II; Sunday, October 15, 1:30 – 3:00 pm PDT About X-linked hypophosphatemia X-linked hypophosphatemia is a rare, lifelong, genetic disease that can impact the bones and muscles in both children and adults. In individuals with XLH, the body doesn't hold on to enough phosphorus, which is an essential mineral for bone health. This is due to the production of excess fibroblast growth factor 23 (FGF23), causing the body to release too much phosphorus through the urine. When phosphorus levels are too low (hypophosphatemia), it can cause the softening and weakening of growing bones in children (rickets) and of mature bones in adults (osteomalacia). In children, XLH typically appears as bowed legs or knock knees. Over time, bone weakening can also lead to bone abnormalities in the legs, delayed growth, and short stature. In adults, XLH may cause osteomalacia, fractures and pseudo-fractures, and hypophosphatemia. About CRYSVITA® (burosumab-twza) Injection CRYSVITA is a recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Kirin, which binds to and inhibits the biological activity of FGF23, the underlying cause of hypophosphatemia in XLH. By blocking FGF23, CRYSVITA helps to restore phosphorus reabsorption in the kidneys and increase the production of active vitamin D, which enhances intestinal absorption of phosphate and calcium. U.S. CRYSVITA Indication CRYSVITA is a fibroblast growth factor (FGF23) blocking antibody indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older. Important Safety Information CONTRAINDICATIONS CRYSVITA is contraindicated: In concomitant use with oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia. When serum phosphorus is within or above the normal range for age. In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism. WARNINGS AND PRECAUTIONS Hypersensitivity Hypersensitivity reactions (e.g., rash, urticaria) have been reported in patients with CRYSVITA. Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment. Hyperphosphatemia and Risk of Nephrocalcinosis Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of nephrocalcinosis. For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on a patient's serum phosphorus levels. Injection Site Reactions Administration of CRYSVITA may result in local injection site reactions. Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment. ADVERSE REACTIONS Pediatric Patients Adverse reactions reported in 10% or more of CRYSVITA-treated pediatric XLH patients across three studies are: pyrexia (55%, 44%, and 62%), injection site reaction (52%, 67%, and 23%), cough (52%), vomiting (41%, 48%, and 46%), pain in extremity (38%, 46%, and 23%), headache (34% and 73%), tooth abscess (34%, 15%, and 23%), dental caries (31%), diarrhea (24%), vitamin D decreased (24%, 37%, and 15%), toothache (23% and 15%), constipation (17%), myalgia (17%), rash (14% and 27%), dizziness (15%), and nausea (10%). Postmarketing experience reported in CRYSVITA-treated pediatric XLH patients: blood phosphorus increased. Adult Patients Adverse reactions reported in more than 5% of CRYSVITA-treated adult XLH patients and in at least 2 patients more than placebo in one study are: back pain (15%), headache (13%), tooth infection (13%), restless legs syndrome (12%), vitamin D decreased (12%), dizziness (10%), constipation (9%), muscle spasms (7%), and blood phosphorus increased (6%). Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. It is unknown if CRYSVITA therapy exacerbates spinal stenosis or spinal cord compression. USE IN SPECIFIC POPULATIONS There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Serum phosphorus levels should be monitored throughout pregnancy. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-844-768-3544. There is no information regarding the presence of CRYSVITA in human milk or the effects of CRYSVITA on milk production or the breastfed infant. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CRYSVITA and any potential adverse effects on the breastfed infant from CRYSVITA or from the underlying maternal condition. PATIENT COUNSELING INFORMATION Advise patients not to use any oral phosphate and/or active vitamin D analog products. Instruct patients to contact their physician if hypersensitivity reactions, injection site reactions, and restless legs syndrome induction or worsening of symptoms occur. You may report side effects to the FDA at (800) FDA-1088 or . You may also report side effects to Kyowa Kirin, Inc. at 1-844-768-3544. For important risk and use information, please see the full Prescribing Information for CRYSVITA. About Kyowa Kirin Kyowa Kirin strives to create and deliver novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company with a more than 70-year heritage, we apply cutting-edge science including expertise in antibody research and engineering, to address the needs of patients and society across multiple therapeutic areas including Nephrology, Oncology, Immunology/Allergy and Neurology. Across our four regions – Japan, Asia Pacific, North America and EMEA/International – we focus on our purpose, to make people smile, and are united by our shared values of commitment to life, teamwork/Wa, innovation, and integrity. You can learn more about the Kyowa Kirin North America at: . SOURCE Kyowa Kirin