Oncogenic Osteomalacia

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).

Pictured: Inside of Kyowa Kirin headquarters/company courtesy Japan-based Kyowa Kirin has opened a new facility in Princeton, NJ, that will serve as its North American headquarters. At almost 80,000 square feet, the facility can accommodate the company’s rapid growth in recent years and will allow it to continue to create jobs for in-office and hybrid workers in the region. Britt Byers, senior vice president of human resources, North America, at Kyowa Kirin, told BioSpace that the company’s headcount has more than doubled since 2018, when the FDA approved Poteligeo (mogamulizumab-kpkc), a treatment for two rare types of non-Hodgkin lymphoma. Since then, the regulator has granted Kyowa Kirin two more approvals: Nourianz (istradefylline) in Parkinson’s disease in 2019 and Crysvita (burosumab) in tumor-induced osteomalacia in 2020. Because of these approvals, the company stated its North America division is now its fastest-growing region in terms of revenue, making up more than one-fourth of the company’s global revenue in 2022, up from 13% in 2019. The region is also growing fast for the company in terms of jobs. Byers said that in 2019, Kyowa Kirin North America had about 280 total employees. Now, that number is up to over 600. The new facility will house over 300 employees working in development, commercial and corporate functions, and will combine teams that were previously split between two locations across New Jersey. Byers said the company expects this growth to continue due to advancements in its current pipeline, which includes rocatinlimab (KHK4083/AMG 451) a mid-stage investigational antibody developed jointly with Amgen to treat moderate-to-severe atopic dermatitis. Byers also said she expects growth to come from future partnerships and alliances the company has yet to announce. New Jersey has seen other growth in the industry of late. Announced May 25, an R&D campus that formerly served as Merck’s global headquarters is set to reopen and become the Northeast Science and Technology (NEST) Center in Kenilworth, NJ, 14 miles outside of New York City. The NEST Center includes 1.4 million square feet of laboratory space and 500,000 square feet of office space. Byers said she’s spent all of her pharma career working in New Jersey. “For me, New Jersey has always been a place where pharma has been ever-present,” Byers said. “It’s not been a challenge for us to find talent when we need it in different areas of expertise.” She added that her team prioritizes diversity in their hiring processes, extending their candidate pools to those without industry experience. “We’re looking for people who want to be a part of creating and building things. . . . We really want people who are ready to roll up their sleeves to engage in different ways and to have their voice heard.”

Kyowa Kirin now leads commercial efforts for CRYSVITA in 40 countries/regions around the world Company commits to keep patient needs at the forefront of commercial and education efforts BEDMINSTER, N.J., April 27, 2023 /PRNewswire/ -- Kyowa Kirin, Inc., an affiliate of Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a top 50 global specialty pharmaceutical company, today assumes primary commercial leadership for CRYSVITA® (burosumab-twza) injection in the United States and Canada from Ultragenyx Pharmaceutical Inc., a transition planned for from the start of their decade-long collaboration. Initially discovered and developed by Kyowa Kirin, CRYSVITA is a first-in-class medicine used to treat adults and children 6 months of age and older with X-linked hypophosphatemia (XLH) and adults and children 2 years of age and older with fibroblast growth factor 23 (FGF23)–related hypophosphatemia in tumor-induced osteomalacia (TIO) when the tumor cannot be located or removed. The transition builds on the company's existing commercial portfolio and commitment to address the needs of people living with rare diseases. "Kyowa Kirin intends to build on the successful launch and broad access that's been established for CRYSVITA." "Our collaboration with Ultragenyx has been a great success for children and adults living with XLH and TIO. Their contributions were instrumental in expediting late-stage trials, securing regulatory approval, and delivering treatment to thousands of patients," said Steve Schaefer, President, Kyowa Kirin North America. "Kyowa Kirin intends to build on the successful launch and broad access that's been established for CRYSVITA, as well as the learnings we have from working alongside XLH and TIO communities around the world, to bring more research, education, and support to patients in North America." To prepare for its new commercial leadership role in North America, Kyowa Kirin has engaged with community leaders and people living with XLH and TIO to gain perspective on their experiences and how best to support them. The company has distilled these conversations into a pledge that articulates how it will act to ensure patient voices are heard and reflected in the company's decision-making going forward. To read the Pledge go here. About the Partnership Kyowa Kirin entered into a collaboration agreement with Ultragenyx in 2013 to hasten late-stage clinical studies and delivery of CRYSVITA to patients. Ultragenyx led Phase 3 studies and took responsibility for launching the medicine in the U.S., Canada, Latin America, and Turkey, while Kyowa Kirin leveraged its global footprint and capabilities to launch CRYSVITA across Europe, Asia, Australia, and the Middle East in addition to global manufacturing and distribution. As part of the agreement, primary commercial responsibility for CRYSVITA in the U.S. and Canada would revert to Kyowa Kirin five years after first commercial use. During this time, the company experienced significant growth in North America, making significant investments in talent, technology, and infrastructure to support its rare disease business and services for patients, including the creation of Kyowa Kirin Cares, its comprehensive patient support program first launched to support the company's oncology franchise. Starting May 1, 2023, all support services for CRYSVITA patients and caregivers in the U.S. will be provided through this program. In addition to leading commercial efforts in Latin America and Turkey, Ultragenyx will continue to work with Kyowa Kirin for the next 12 months, providing support for some commercial activities in North America. About XLH and TIO X-linked hypophosphatemia is a rare, lifelong, genetic disease that can impact the bones and muscles in both children and adults. Tumor-induced osteomalacia is an extremely rare, difficult-to-diagnose disease caused by slow-growing tumors that occur throughout the body. In XLH and TIO, 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. Patients with TIO may develop multiple bone abnormalities and can experience symptoms including severe hypophosphatemia, osteomalacia, and fractures. Symptoms are progressive and can lead to long-term disabilities, so it is vital that TIO be treated as soon as possible. About CRYSVITA 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 and TIO. 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 prescription medicine used to treat adults and children 6 months of age and older with X-linked hypophosphatemia and adults and children 2 years of age and older with fibroblast growth factor 23 (FGF23)–related hypophosphatemia in tumor-induced osteomalacia when the tumor cannot be located or removed. Important Safety Information You should not take CRYSVITA if: You take an oral phosphate supplement and/or a specific form of vitamin D supplement (such as calcitriol, paricalcitol, doxercalciferol, calcifediol). Your phosphorus levels from a blood sample are within or above the normal range for age. You have kidney problems. What is the most important information you should know about CRYSVITA? Some patients developed allergic reactions (e.g., rash and hives) while taking CRYSVITA. Your doctor will monitor you for symptoms of an allergic reaction while you are taking CRYSVITA. High levels of phosphorus in the blood have been reported in some patients taking CRYSVITA. This may be related to a risk of high calcium levels in the kidneys. Your doctor will collect blood samples to monitor your levels. Administration of CRYSVITA may result in reactions at the injection site, such as hives, reddening of the skin, rash, swelling, bruising, pain, severe itching of the skin, and collection of blood outside of a blood vessel (i.e., hematoma). If you are taking CRYSVITA for TIO, your doctor will have you stop your CRYSVITA treatment temporarily if you are undergoing treatment for your tumor (e.g., surgical removal of the tumor or radiation therapy). What are the possible side effects of CRYSVITA? Adverse reactions that were seen in children with XLH are: Adverse reactions that were seen in adults with XLH are: Narrowing of the spaces within the spine is common in adults with XLH, and pressure on the spinal cord has been reported in adults taking CRYSVITA. It is not known if taking CRYSVITA worsens the narrowing of the spaces within the spine or the pressure on the spinal cord. Adverse reactions that were seen in adults with TIO are: Before taking CRYSVITA, tell your doctor about all of your medications (including supplements) and medical conditions, including if you: Are taking oral phosphate and/or active vitamin D (such as calcitriol, paricalcitol, doxercalciferol, calcifediol). Are pregnant, think you may be pregnant, or plan to become pregnant. There is not enough experience to know if CRYSVITA may harm your unborn baby. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-844-768-3544. Are breastfeeding or plan to breastfeed. There is not enough experience to know if CRYSVITA passes into your breast milk. Talk with your doctor about the best way to feed your baby while you receive CRYSVITA. While taking CRYSVITA, tell your doctor if you experience: An allergic reaction such as rash or hives A rash, swelling, bruising, or other reaction at the injection site New or worsening restless legs syndrome These are not all the possible side effects of CRYSVITA. Call your doctor for medical advice about side effects. 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. 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: . Company Codes: Tokyo:4151, OTC-PINK:KYKOY