Burosumab-TWZA

Preliminary 2025 total revenue of $672 million to $674 million, exceeding top end of guidance Preliminary cash and investments of approximately $735 million as of December 31, 2025 Anticipated 2026 catalysts include two potential approvals and pivotal Phase 3 data from the GTX-102 Phase 3 Aspire study for Angelman syndrome NOVATO, Calif., Jan. 12, 2026 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultra-rare genetic diseases, today reported preliminary unaudited 2025 revenue results, cash and investments at year end 2025, and provided a corporate update. “In 2025, we delivered another year of significant revenue growth, with preliminary revenue exceeding the top end of guidance," said Emil Kakkis, chief executive officer and president of Ultragenyx. "The year ahead will be transformational for our company and the rare disease communities we serve, with two potential gene therapy approvals of first-ever treatments, and a pivotal data readout from our Phase 3 program in Angelman syndrome, setting the stage for our next phase of growth." Financial Update 2025 Preliminary Revenue (unaudited) Total revenue for 2025 is estimated to be $672 million to $674 million, which exceeds the top end of the guidance range, and represents approximately 20% growth versus 2024. Crysvita ® revenue for 2025 is estimated to be $480 million to $482 million, which exceeds the top end of the guidance range, and represents approximately 17% growth versus 2024. Dojolvi ® revenue for 2025 is estimated to be $95 million to $97 million, at the midpoint of the guidance range, and represents approximately 9% growth versus 2024. 2025 Ending Cash Position (unaudited) Cash and investments were approximately $735 million as of December 31, 2025. The 2025 revenues and cash position included in this release are preliminary and are therefore subject to adjustment. The preliminary revenue results are based on management’s initial analysis of operations for the year ended December 31, 2025. The Company expects to issue financial guidance for fiscal year 2026, including details on previously announced planned expense reductions, and full financial results for the fourth quarter and fiscal year 2025, in February 2026. 2026 Clinical and Regulatory Catalysts DTX401 (pariglasgene brecaparvovec) AAV gene therapy for glycogen storage disease type Ia (GSDIa): Biologics License Application (BLA) rolling submission completed in December 2025, with an anticipated PDUFA date in the third quarter of 2026. UX111 (rebisufligene etisparvovec) AAV gene therapy for Sanfilippo syndrome type A (MPS IIIA): Resubmission of the BLA is on track for early in 2026 and will be followed by an up to 6-month review per FDA regulations. GTX-102 (apazunersen) antisense oligonucleotide (ASO) for the treatment of Angelman syndrome (AS): Data from the fully enrolled, pivotal, Phase 3 Aspire study in patients with a genetically confirmed diagnosis of UBE3A deletion is expected in the second half of 2026. The Phase 2/3 Aurora study is also underway in other genotypes and ages, with first patient dosed in October 2025. UX701 (rivunatpagene miziparvovec) AAV gene therapy for Wilson disease: Enrollment is complete for the fourth cohort in the ongoing, dose-finding stage of the pivotal Cyprus2+ study. Data are expected in the first half of 2026. Data from the Phase 3 Orbit and Cosmic studies of UX143 (setrusumab) in osteogenesis imperfecta, including data on bone mineral density, vertebral fractures, and patient reported outcomes on pain and physical function, will be presented at the J.P. Morgan Healthcare Conference. The company presentation is scheduled for Monday, January 12, 2026 at 10:30 AM PT. The live and archived webcast of the presentation will be accessible from the company’s website at . About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease. The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency. For more information on Ultragenyx, please visit the company's website at: . Forward-Looking Statements and Use of Digital Media Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, the components and timing of regulatory submissions and the timing of results from ongoing clinical studies are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause the company’s clinical development programs, commercial success of its products and product candidates, continued collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, risks related to serious or undesirable side effects of our product candidates, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, our limited experience in generating revenue from product sales, risks related to product liability lawsuits, our dependence on Kyowa Kirin for the commercialization of Crysvita in certain major markets, including the U.S. and Canada, and for our commercial supply of Crysvita in those markets, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, , smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, our ability to successfully manage the expansion of our company, competition from other therapies or products, regulatory scrutiny of the company’s products and product candidates, the company’s limited experience as a company in operating its own manufacturing facility, market acceptance of our products, uncertainty related to insurance coverage and reimbursement, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidate. Ultragenyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 4, 2025, and its subsequent periodic reports filed with the SEC. In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website ( ) and LinkedIn website ( ). Contacts Ultragenyx Pharmaceutical Inc. Investors Joshua Higa ir@ultragenyx.com Media Jess Rowlands media@ultragenyx.com

协和麒麟宣布布罗索尤单抗获中国上市批准，标志着国内首个罕见病药物商业化引进，填补X连锁低磷血症治疗领域空白，彰显其推动罕见病治疗的决心。 2021年1月5日，协和麒麟（中国）制药有限公司宣布，其引进的布罗索尤单抗（Burosumab）已获得中国国家药品监督管理局的上市批准。这款药物作为首个在中国商业化引进的罕见病药物，是专门针对X连锁低磷血症（XLH）的生物制剂，填补了国内在这一领域的空白。布罗索尤单抗的获批，不仅标志着XLH治疗进入了新纪元，更彰显了协和麒麟在推动罕见病治疗方面的坚定决心。 X连锁低磷性佝偻病是一种遗传性磷代谢失调性疾病，主要表现为低磷血症和骨骼矿化障碍，导致严重骨骼畸形和健康风险。 低磷性佝偻病，尤其是X连锁低磷性佝偻病（XLH），是一种遗传性磷代谢失调性疾病，以低磷血症和骨骼矿化障碍为主要特征。该病不仅会导致骨骼畸形、生长迟缓等严重后果，还会增加致残、致畸的风险。尽管目前XLH在国内的具体发病率尚不明确，但已被列入国家《第一批罕见病目录》，显示出其罕见且严重的特性。布罗索尤单抗的上市，无疑将为这类患者带来新的治疗选择和希望。 布罗索尤单抗是一种全人源化IgG1单克隆抗体，通过靶向抑制FGF23的活性，提高血清磷浓度，改善骨骼矿化，实现标本兼治的对因治疗。 目前，已有超过400种PHEX基因突变位点被报道，这些突变均会影响PHEX蛋白的功能，进而导致疾病的发生。这些突变的PHEX基因会干扰成纤维细胞生长因子23（FGF23）的降解过程，使得其在循环中的水平升高。FGF23主要由成骨细胞和骨细胞分泌，是一种维持体内磷稳态的关键激素。它通过促进肾脏磷酸盐的排泄和抑制肠道磷的吸收，共同发挥下调血磷的作用。然而，体内FGF23的过量蓄积正是导致低磷血症的根本原因。 目前，全球首个获得批准的靶向FGF23新药——布罗索尤单抗，已问世。布罗索尤单抗在成人和儿童患者中临床试验结果显著，提高血清磷水平，显著改善疼痛和关节僵硬，治疗效果优于传统方法。 在临床实践中，XLH的传统治疗方法主要依赖于磷酸盐和活性维生素D的补充，然而这些治疗手段并非针对疾病的根本原因，且需要频繁用药。尽管如此，其治疗效果往往有限，并可能引发诸如肾钙质沉积症、高钙尿症以及继发性甲状旁腺功能亢进等副作用，这些副作用会导致尿磷排泄增加，从而进一步加剧骨骼疾病。 布罗索尤单抗作为一种全人源化的IgG1单克隆抗体，其独特之处在于能够精准地靶向结合并抑制FGF23的活性。通过这一作用机制，该药物能够阻断FGF23的下游信号通路，进而增加肾脏对磷的重吸收能力，并提升血清中活性维生素D的水平。此外，它还能促进肠道对磷酸盐和钙的吸收，从而提高血清磷的浓度，为骨骼矿化提供必要的物质基础，并最终减少骨骼疾病的发生。因此，布罗索尤单抗可视为一种标本兼治的对因治疗药物。 在临床试验中，布罗索尤单抗展现出了显著的有效性和安全性。耶鲁大学医学院于2018年发布了一项成人XLH多中心的Ⅲ期临床试验结果，证实了与安慰剂相比，布罗索尤单抗能够显著提升血清磷水平，并改善疼痛和关节僵硬的症状。经过24周的治疗，接受布罗索尤单抗治疗的患者中，43.1%的活动性骨折和假性骨折均实现了完全愈合，这一比例远高于安慰剂组的7.7%。同时，布罗索尤单抗治疗组的不良反应与安慰剂组相比，并未出现显著差异。 布罗索尤单抗已在全球多地获批用于治疗XLH及其他低血磷性疾病，并扩展至小婴儿，成为首个治疗XLH的创新药物。 2019年，《柳叶刀》杂志上发表了一项关于儿童XLH的随机、多中心、与传统治疗对照的Ⅲ期临床试验结果。该研究显示，相较于传统治疗组，接受布罗索尤单抗治疗的患者在血清磷水平上得到了显著提升，佝偻病症状得到了有效改善，生长正常，运动能力逐渐恢复。经过40周的治疗，布罗索尤单抗组患者的影像学总体印象变化评分（RGI-C）的改善情况明显优于传统治疗组。到了64周时，两组患者的RGI-C评分均持续改善，但布罗索尤单抗组的改善程度依然显著高于传统治疗组（RGI-C改善≥2分的患者比例，87% vs 19%，p0.001）。在整个试验过程中，不良反应均为轻度或中度，且布罗索尤单抗组未出现导致停药的不良药物反应，进一步证明了其安全性。 临床试验进一步证明了布罗索尤单抗在成人与儿童患者中对XLH的显著疗效与安全性，为全球患者提供治疗新方案。 相较于传统治疗，布罗索尤单抗在改善RGI-C总评分方面展现出了显著优势。 一名男婴在18个月大时开始接受每两周一次的布罗索尤单抗治疗，其影像学检查结果显示，在第40周时佝偻病症状已有显著改善。这一成果证明了布罗索尤单抗在治疗XLH方面的有效性。此外，布罗索尤单抗在2018年1月和4月分别获得欧盟和美国的批准，用于治疗1岁及以上儿童和成年人的XLH。该药物在美国和欧盟均被授予孤儿药资格，并在美国获得突破性药物资格。最近，美国FDA再次批准了布罗索尤单抗的适应症标签扩展，纳入新的临床数据，显示其治疗XLH儿科患者的疗效优于口服磷酸盐和活性维生素D，同时，在长期治疗的成人患者中也能改善僵硬症状并维持疗效。目前，布罗索尤单抗的适用年龄已扩展至6个月大的婴儿。此外，该药物还被开发用于治疗与FGF23相关的低血磷性疾病，成为首个获FDA批准治疗XLH和肿瘤诱导的骨软化症(TIO)的创新药物，已在美国、欧洲、日本等地上市。 专家指出，布罗索尤单抗的出现为XLH患者带来了全新治疗希望，可直接针对病因治疗，并显著改善生活质量。 夏维波教授，作为北京协和医院内分泌科主任及中华医学会骨质疏松和骨矿盐疾病分会的前任主任委员，对XLH这一致残、致畸性疾病有着深入的了解。XLH患者成年后，会面临骨痛、肌肉疼痛以及关节活动受限等骨软化症状的困扰。这种疾病源于慢性低磷血症引发的骨矿化缺陷，不仅损害患者的行动能力，还严重影响其日常生活质量。过去，传统疗法往往只能缓解症状，无法针对病因进行治疗，且常伴有多种并发症，治疗效果因而受到限制。然而，布罗索尤单抗的出现改变了这一现状。作为国内首个且全球唯一的FGF23生物制剂，它能够直接作用于XLH的病因，为患者提供全新的治疗选择。这一创新药物的上市，无疑为我国的XLH患者带来了全新的治疗希望。 章振林教授，作为上海交通大学附属第六人民医院骨质疏松和骨病专科的权威，同时也是上海市骨疾病临床研究中心的主任和中华医学会骨质疏松和骨矿盐疾病分会的领军人物，对XLH这一疾病有着深刻的洞见。他指出，成人XLH患者往往在儿童时期就已出现误诊或漏诊的情况，导致他们长期遭受骨痛、骨骼畸形、骨折及假性骨折、关节疼痛与僵硬、骨关节炎早期症状、牙周脓肿以及听力损害等病症的困扰。这些症状不仅严重影响患者的行动能力，还可能导致身体功能全面衰退，生活质量大幅下降，甚至丧失劳动能力。幸运的是，全球首个靶向FGF23的新药——布罗索尤单抗的问世，为XLH患者带来了全新的治疗希望。这种药物能够直接针对XLH的病因进行治疗，为患者带来持久且显著的疗效。