Medroxyprogesterone Acetate

Treatment with PALYNZIQ led to statistically significant blood phenylalanine (Phe) lowering compared to diet alone in pivotal Phase 3 PEGASUS study PALYNZIQ is the only enzyme substitution therapy approved for the treatment of people with PKU SAN RAFAEL, Calif., Feb. 27, 2026 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced that the U.S. Food and Drug Administration (FDA) has approved the company's supplemental Biologics License Application (sBLA) for PALYNZIQ® (pegvaliase-pqpz) to include pediatric patients 12 years of age and older with phenylketonuria (PKU). PALYNZIQ is the only enzyme substitution therapy approved to reduce blood phenylalanine (Phe) concentrations in people with PKU. "Adolescence is a period of increasing independence and academic demands, and represents a particularly challenging time for individuals with PKU. The ultra-restrictive diet required for PKU management may become unsustainable, and poor blood Phe control leads to adverse neurocognitive outcomes. PALYNZIQ is the only genotype-independent medication which may bring Phe into the normal range while allowing an unrestricted diet," said Stephanie Sacharow, M.D., Director, Dr. Harvey Levy Program for PKU and Related Conditions, Boston Children's Hospital. "In my clinic we have found that PALYNZIQ treatment adherence is even more successful in teens under age 18, while they are living at home with family support, and this approval allows us to extend this therapeutic option to adolescents who may benefit most." The FDA approval is based on data from PEGASUS, a Phase 3 multi-center open-label randomized controlled study evaluating the safety and efficacy of PALYNZIQ compared to diet alone in adolescents aged 12 to <18 with PKU who had uncontrolled blood Phe concentrations greater than 600 µmol/L on existing management. Individuals in the PALYNZIQ arm showed a significant mean reduction from baseline in blood Phe levels at Week 72 compared to those in the diet only arm (Table 1). "Today's FDA approval for PALYNZIQ is an important step forward for the PKU community, providing a new option for adolescents ages 12 and older that has the potential to improve daily PKU management," said Catherine Warren, Executive Director of the National PKU Alliance. "Adolescence is a time of major change for people living with PKU, and having PALYNZIQ available better sets teenagers up for success with managing their blood phenylalanine levels as they navigate the transition into adulthood." As was recently presented at the 15th International Congress of Inborn Errors of Metabolism, by the end of Part 1 almost half of participants (44.4%) reached levels below guideline recommendations. Of those individuals, 75% were below 120 µmol/L and their average Phe reduction was 828 µmol/L (94% reduction in blood Phe from baseline). Nine participants whose blood Phe levels were below 30 µmol/L (hypophenylalaninemia) were able to increase their intact protein intake by 318.1% from baseline (SD=195.4; min=1.42, max=542.5) and decrease their intake of medical food protein by 55.16% (SD=56.4; min=-100, max=60.3); six individuals discontinued medical food completely. The most common adverse reactions (≥20%) with PALYNZIQ in adolescents were injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue and pain in extremity. As in previous clinical studies, the overall safety profile of PALYNZIQ observed in adolescents showed most reactions occurring in the induction/titration phase and decreasing in frequency during the maintenance phase. "Over the past two decades, BioMarin has been working hand-in-hand with the medical and advocacy communities to improve the lives of people living with PKU, including introduction of the first two treatment options for this inherited metabolic condition that otherwise requires lifelong adherence to a rigid medical diet," said Greg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin. "We are proud to build on this legacy by expanding PALYNZIQ's approval to adolescents as young as age 12, which will allow even more people with PKU the prospect of achieving substantially lower Phe levels." The company is also seeking approval from the European Medicines Agency with the goal of expanding treatment with PALYNZIQ to include adolescents as young as age 12 in the European Union. Dr. Stephanie Sacharow has participated in speaking engagements and served on advisory boards for BioMarin. About PALYNZIQ PALYNZIQ substitutes the deficient phenylalanine hydroxylase (PAH) enzyme in PKU with a PEGylated version of the enzyme phenylalanine ammonia lyase to break down Phe. PALYNZIQ is administered using a dosing regimen designed to facilitate tolerability; PALYNZIQ's safety profile consists primarily of immune-mediated responses, which can include anaphylaxis, for which robust risk management measures effective in clinical trials are in place. See the full Prescribing Information, which includes a Boxed Warning. PALYNZIQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PALYNZIQ REMS, because of the risk of anaphylaxis. Further information, including a list of qualified pharmacies, is available at or by telephone 1-855-758-REMS (1-855-758-7367). PALYNZIQ is approved for the treatment of PKU in more than 35 countries worldwide. Patient Support Accessing PALYNZIQ To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-866-906-6100 or e-mail [email protected]. For more information about PALYNZIQ, please visit . For additional information regarding this product, please contact BioMarin Medical Information at [email protected]. About Phenylketonuria PKU, or phenylalanine hydroxylase (PAH) deficiency, is a genetic condition affecting approximately 70,000 people in the regions of the world where BioMarin operates. The PAH enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If functional enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems and psychiatric symptoms. As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU born after this period in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after. PKU can be managed with a severe Phe-restricted diet, supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most individuals to adhere to this strict diet to the extent needed to achieve adequate control of blood Phe levels. Dietary control of Phe in childhood can prevent major developmental issues and neurological consequences, but poor Phe control in adolescence and adulthood is associated with a range of neuropsychological deficits and functional impairment. PALYNZIQ U.S. Indication and Important Safety Information PALYNZIQ® (pegvaliase-pqpz) is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood Phe concentrations greater than 600 micromol/L (10 mg/dL) on existing management. BOXED WARNING: ANAPHYLAXIS Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment. Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient's and observer's (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer epinephrine, if needed. Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer epinephrine, and call for emergency medical support upon its use. Prescribe epinephrine for all patients treated with PALYNZIQ. Prior to the first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry epinephrine with them at all times during PALYNZIQ treatment. PALYNZIQ is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Further information, including a list of qualified pharmacies, is available at PALYNZIQREMS.com or by telephone at 1-855-758-REMS (1-855-758-7367). WARNINGS AND PRECAUTIONS Anaphylaxis Signs and symptoms of anaphylaxis reported include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat swelling or tightness, flushed or red skin, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea). Anaphylaxis generally occurred within 1 hour after injection; however, delayed episodes occurred up to 48 hours after PALYNZIQ administration. Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. In clinical trials of primarily adult patients with an induction/titration/maintenance dosage regimen, 29/285 (10%) experienced a total of 42 anaphylaxis episodes. In a clinical trial of patients 12 to less than 18 years of age, 4/36 (11%) of PALYNZIQ-treated patients experienced 1 episode of anaphylaxis. Other Hypersensitivity Reactions Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgment of the healthcare provider. In clinical trials of primarily adult patients taking PALYNZIQ, hypersensitivity reactions, other than anaphylaxis, were reported in 204/285 (72%) of patients. In a clinical trial of patients 12 to less than 18 years old taking PALYNZIQ, these reactions were reported in 12 out of 36 (33%) of patients. Injection Site Infections Serious injection site infections including abscess, cellulitis, necrosis, and ulcer have been reported. Some cases required hospitalization, surgical debridement, intravenous antibiotics, and discontinuation of PALYNZIQ. Provide proper training to patients and/or caregivers on the use of aseptic injection technique, injection site rotation and to check the site for redness, swelling, or tenderness. Instruct patients to contact their healthcare provider if signs or symptoms of an infection develop, persist, or worsen. Hypophenylalaninemia (HypoPhe) Some patients have experienced HypoPhe; monitor blood Phe levels periodically during treatment. Frequent blood Phe monitoring is recommended in the pediatric population. For blood Phe concentrations below 30 micromol/L, the dosage of PALYNZIQ may be reduced and/or dietary protein and Phe intake may be modified to maintain blood Phe concentrations within a clinically acceptable range and above 30 micromol/L. ADVERSE REACTIONS The most common adverse reactions in clinical trials of primarily adult patients (at least 20% in either treatment phase) were injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety. Arthralgia: In clinical trials, 245 out of 285 (86%) primarily adult patients experienced episodes consistent with arthralgia (includes back pain, musculoskeletal pain, pain in extremity, and neck pain). Injection site reactions were reported as early as after the first dose of PALYNZIQ and occurred at any time during treatment. Generalized Skin Reactions: In clinical trials, 134 out of 285 (47%) primarily adult patients treated with PALYNZIQ experienced generalized skin reactions (not limited to the injection site) lasting at least 14 days. Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) primarily adult patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema, and face edema) occurring independent of anaphylaxis. In clinical trials, serum sickness was reported in 7 out of 285 (2%) primarily adult patients. In the clinical trials, adverse reactions were associated with treatment discontinuation, dosage reduction and temporary drug interruption. In the 285 primarily adult patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. Pediatric Patients: In a clinical study of 55 patients aged 12 to less than 18 years of age, the most common adverse reactions (at least 20% and greater than in control) were injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue, and pain in extremity. Two patients (5.6%) discontinued treatment due to adverse reactions. Blood Phenylalanine Monitoring and Diet Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe concentrations during maintenance therapy. Counsel patients to monitor dietary protein and Phe intake, and adjust as directed by their healthcare provider. DRUG INTERACTIONS Effect of PALYNZIQ on Other PEGylated Products In a single-dose study of PALYNZIQ in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced a hypersensitivity reaction. One of the two patients experienced anaphylaxis The clinical effects of concomitant treatment with different PEGylated products are unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis USE IN SPECIFIC POPULATIONS Pregnancy and Lactation Available data do not establish an increased risk of adverse developmental outcomes to the fetus exposed to PALYNZIQ. Advise women who are exposed to PALYNZIQ during pregnancy or who become pregnant within one month following the last dose of PALYNZIQ that there is a pregnancy surveillance program that monitors pregnancy outcomes. Healthcare providers should report PALYNZIQ exposure and encourage these patients to report their pregnancy to BioMarin (1-866-906-6100). Monitor blood Phe levels in breastfeeding women treated with PALYNZIQ to ensure maintenance of blood Phe <360 micromol/L. Adjust dosage and/or dietary protein and Phe intake as needed to avoid concentrations below 30 micromol/L. Pediatric & Geriatric Use: The safety and effectiveness of PALYNZIQ in pediatric patients from birth to less than 12 years have not been established. Clinical studies of PALYNZIQ did not include patients aged 65 years and older. You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to the FDA at 1-800-FDA-1088 or . Please see accompanying full Prescribing Information, including Boxed Warning. About BioMarin BioMarin is a leading, global rare disease biotechnology company focused on delivering medicines for people living with genetically defined conditions. Founded in 1997, the San Rafael, California-based company has a proven track record of innovation, with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that have a profound impact on patients. To learn more, please visit . Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: the approval of BioMarin's supplemental Biologics License Application (sBLA) for PALYNZIQ for adolescents 12 years of age and older with phenylketonuria (PKU) by the U.S. Food and Drug Administration (FDA), including the safety profile and potential benefits of PALYNZIQ for adolescents and the potential to fundamentally change the way adolescents manage PKU in their daily lives; BioMarin's work with the European Medicines Agency (EMA) with the goal of expanding treatment with PALYNZIQ to include adolescents as young as age 12 in the European Union; and the continued clinical development of PALYNZIQ. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others, results and timing of current and planned preclinical studies and clinical trials of PALYNZIQ; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the FDA, the EMA, the European Commission and other regulatory authorities, and those factors detailed in BioMarin's filings with the Securities and Exchange Commission (SEC), including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the year ended December 31, 2025, as such factors may be updated by any subsequent filings with the SEC. Investors are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin®, BioMarin RareConnections® and PALYNZIQ® are registered trademarks of BioMarin Pharmaceutical Inc. SOURCE BioMarin Pharmaceutical Inc. 21% more press release views with Request a Demo

肌苷-5'-单磷酸脱氢酶（IMPDH）在生物化学领域的运用非常广泛且深入，其核心在于它作为嘌呤代谢途径中的一个关键限速酶。它可以催化肌苷-5'-单磷酸（IMP）转化为黄苷-5'-单磷酸（XMP），这是鸟嘌呤核苷酸（GTP）从头合成的第一步，也是关键步骤。由于GTP在DNA/RNA合成、信号转导、能量代谢和蛋白质合成中不可或缺，导致IMPDH的活性直接调控着细胞的生长与增殖。当前，IMPDH在生物化学领域的运用主要体现在以下三个核心层面：1. 基础理论研究：揭示酶学机理与细胞代谢调控IMPDH作为一个结构复杂、调控精妙的模型，是研究酶动力学、变构调节和蛋白质动态构象变化的热点。酶催化机制研究：IMPDH的催化反应包含两步：首先形成共价的E-XMP*中间体，然后水解产生XMP。其复杂的反应动力学，特别是对底物IMP的协同性（cooperativity），是研究的重点。最新研究发现，这种协同性受pH值影响，并由IMP驱动催化结构域之间的相互作用介导。变构调控机制解析：IMPDH含有一个调节性CBS结构域，是该领域研究变构调控的经典范例。近期研究利用冷冻电镜（cryo-EM） 技术，首次详细揭示了细菌IMPDH的变构调节分子机制。例如，在分枝杆菌中，GTP或细菌 stringent response 信号分子 (p)ppGpp 与CBS结构域结合，会将整个酶锁定在一种压缩的、无活性的八聚体构象，从而阻止底物IMP进入活性位点。而ATP可以竞争性地取代它们，解除抑制，允许酶转变为活性构象。高级结构动态研究：借助结构生物学，科学家发现IMPDH在催化循环中会在四聚体和八聚体之间动态转换。最新的研究甚至观察到了由酶自身C末端形成的、调控酶活性的"中心桶状结构"，这为理解其复杂的构象变化和自调控机制提供了全新视角。2. 药物开发应用：作为关键的药物靶点由于IMPDH对细胞增殖至关重要，它已成为开发抗菌、抗病毒、抗肿瘤及免疫抑制药物的黄金靶点。抗菌药物研发：IMPDH是开发新型抗生素，特别是针对耐药性病原菌（如结核分枝杆菌）的热门靶点。由于细菌与人类IMPDH存在结构差异，科学家正致力于开发能选择性抑制细菌IMPDH的小分子药物。对细菌IMPDH独特变构机制（如GTP/ppGpp结合位点、独特的八聚体界面）的深入理解，为设计高选择性变构抑制剂开辟了新途径。抗肿瘤与免疫抑制：最经典的例子是麦考酚酸（MPA），它是一种有效的IMPDH抑制剂，作为免疫抑制剂广泛应用于器官移植后抗排斥反应。近期研究还发现，IMPDH是脑转移肿瘤细胞的代谢脆弱点，抑制IMPDH能有效遏制肺癌、乳腺癌等脑转移的发展，IMPDH的表达水平甚至可能作为预测脑转移风险的生物标志物。抗病毒研究：病毒自身不携带嘌呤合成酶，完全依赖宿主细胞提供核苷酸。因此，靶向宿主IMPDH以消耗GTP库，成为广谱抗病毒策略之一。例如，有研究通过计算方法针对人IMPDH2型进行药物设计，以期找到抗登革热的先导化合物。3. 研究工具运用：作为生物试剂在具体的实验研究中，IMPDH及其底物是重要的生物化学试剂。酶学分析工具：纯化的IMPDH蛋白常用于酶动力学测定和抑制剂筛选实验。研究人员通过测定NAD⁺还原为NADH的速率来评估酶的活性和化合物的抑制效果。标准底物与抑制剂：其天然底物肌苷-5'-单磷酸（IMP） 及其盐形式（如IMP二钠盐）是商业化的标准生化试剂，用于体外酶活测定实验。同时，特异性抑制剂（如MPA）也常被用作工具药，在细胞实验中用于阻断GTP合成通路，以研究细胞增殖、分化等生物学过程。总结来说，肌苷-5'-单磷酸脱氢酶不仅作为嘌呤代谢通路中的核心酶，是理解细胞生长调控的钥匙，更是连接基础酶学研究与转化医学（特别是抗感染和抗肿瘤药物研发）的重要桥梁。在此 我们提供自己的试剂产品数据作为参考肌苷-5'-单磷酸脱氢酶/Inosine Monophosphate/ Inosine-5'-Monophosphate Dehydrogenase Liquid ≥100U/mg protein中文名称：肌苷-5'-单磷酸脱氢酶英文名称：Inosine MonophosphateEC：1.1.1.205CAS：9028-93-7Purity：≥90%Specific Activity：≥100U/mg proteinUnit Definition：One unit oxidizes 1.0 umol 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP) per min in the presence of beta-NAD（E0070） at pH 7.4 at 25 degC性状：液体用途：生化研究保存：2-8℃如果想要了解更多产品信息或者需要该产品 请点击下方链接