A Phase II, Escalating Dose, Open Label Study to Evaluate the Safety of Triheptanoin for the Prevention of Hypoglycemia in Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)

This is a medical research study to test a medication in adult patients with a disease called medium-chain acyl-CoA dehydrogenase deficiency (MCADD). The medication is triheptanoin, which is currently FDA approved for the treatment of Long-Chain Fatty Acid Oxidation Disorders. Previous research suggests that triheptanoin may also be effective in the treatment MCADD. This study will investigate the safety and efficacy (how well it works) of triheptanoin in patients with MCADD.

开始日期2024-08-01

申办/合作机构

University of Pittsburgh

[+1]

NCT06340685 / Recruiting临床1期IIT

An Open Label, Exploratory, Proof-of Concept Study of Triheptanoin as Treatment for Patients With Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency

This is a medical research study to test a medication in patients with a disease called Pyruvate Dehydrogenase Complex (PDC) Deficiency. The medication is triheptanoin, which is currently FDA approved for the treatment of Long-Chain Fatty Acid Oxidation Disorders. Previous research suggests that triheptanoin may also be effective in the treatment PDC Deficiency. This study will investigate the safety and efficacy (how well it works) of triheptanoin in patients with PDC Deficiency.

开始日期2024-05-01

申办/合作机构

University of Pittsburgh

[+1]

NCT05933200 / Recruiting临床3期

A Randomized, Double-blind, Multicenter Study to Determine the Effect of Triheptanoin Compared With Even-chain, Medium-chain Triglycerides (MCT) on Major Clinical Events (MCEs) in Pediatric Patients With Long-chain Fatty Acid Oxidation Disorders (LC-FAOD)

The main goal of this study is to evaluate the effects of triheptanoin versus Medium-chain Triglycerides (MCT) on frequency of Major Clinical Events (MCEs).

开始日期2023-02-28

申办/合作机构

Ultragenyx Pharmaceutical, Inc.

100 项与三庚酸甘油酯相关的临床结果

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100 项与三庚酸甘油酯相关的转化医学

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100 项与三庚酸甘油酯相关的专利（医药）

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项与三庚酸甘油酯相关的文献（医药）

2024-02-01·Chemosphere

Assessment of endocrine disruptor impacts on lipid metabolism in a fatty acid-supplemented HepaRG human hepatic cell line

Article

作者: Degerli, Selenay ; Bernal, Kévin ; Touma, Charbel ; Martin-Chouly, Corinne ; Lagadic-Gossmann, Dominique ; Rose, Sophie ; Le-Grand, Béatrice ; Blanc, Etienne B ; Coumoul, Xavier ; Langouët, Sophie ; Genêt, Valentine

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. This disease encompasses several stages, from steatosis to steatohepatitis and, eventually, to fibrosis and cirrhosis. Exposure to environmental contaminants is one of the risk factors and an increasing amount of evidence points to a role for endocrine disrupting compounds (EDCs). This study assesses the impact of selected EDCs on the formation of lipid droplets, the marker for steatosis in a hepatic model. The mechanisms underlying this effect are then explored. Ten compounds were selected according to their obesogenic properties: bisphenol A, F and S, butyl-paraben, cadmium chloride, p,p'-DDE, DBP, DEHP, PFOA and PFOS. Using a 2D or 3D model, HepaRG cells were exposed to the compounds with or without fatty acid supplementation. Then, the formation of lipid droplets was quantified by an automated fluorescence-based method. The expression of genes and proteins involved in lipid metabolism and the impact on cellular respiration was analyzed. The formation of lipid droplets, which is revealed or enhanced by oleic acid supplementation, was most effectively induced by p,p'-DDE and DEHP. Experiments employing either 2D or 3D culture conditions gave similar results. Both compounds induced the expression of PLIN2. p,p'-DDE also appears to act by decreasing in fatty acid oxidation. Some EDCs were able to induce the formation of lipid droplets, in HepaRG cells, an effect which was increased after supplementation of the cells with oleic acid. A full understanding of the mechanisms of these effects will require further investigation. The novel automated detection method described here may also be useful in the future as a regulatory test for EDC risk assessment.

2024-02-01·European Journal of Medicinal Chemistry

Design, synthesis and biological evaluation of carbamate derivatives incorporating multifunctional carrier scaffolds as pseudo-irreversible cholinesterase inhibitors for the treatment of Alzheimer's disease

Article

作者: Jia, Hongwei ; Ma, Chao ; Zhao, Xueqi ; Yang, Huali ; Hu, Dexiang ; Li, Zhenli ; Wang, Ningwei ; Liu, Yaoyang ; Li, Yingbo ; Zhang, Ruiwen ; Liu, Peng ; Wang, Hanxun ; Xiu, Xiaomeng ; Cheng, Maosheng ; Cui, Tao ; Li, Mengzhen

In this study, a series of carbamate derivatives incorporating multifunctional carrier scaffolds were designed, synthesized, and evaluated as potential therapeutic agents for Alzheimer's disease (AD). We used tacrine to modify the aliphatic substituent, and employed rivastigmine, indole and sibiriline fragments as carrier scaffolds. The majority of compounds exhibited good inhibitory activity for cholinesterase. Notably, compound C7 with sibiriline fragment exhibited potent inhibitory activities against human acetylcholinesterase (hAChE, IC₅₀ = 30.35 ± 2.07 nM) and human butyrylcholinesterase (hBuChE, IC₅₀ = 48.03 ± 6.41 nM) with minimal neurotoxicity. Further investigations have demonstrated that C7 exhibited a remarkable capacity to safeguard PC12 cells against H₂O₂-induced apoptosis and effectively suppressed the production of reactive oxygen species (ROS). Moreover, in an inflammation model of BV2 cells induced by lipopolysaccharide (LPS), C7 effectively attenuated the levels of pro-inflammatory cytokines. After 12 h of dialysis, C7 continued to exhibit an inhibitory effect on cholinesterase activity. An acute toxicity test in vivo demonstrated that C7 exhibited a superior safety profile and no hepatotoxicity compared to the parent nucleus tacrine. In the scopolamine-induced AD mouse model, C7 (20 mg/kg) significantly reduced cholinesterase activity in the brain of the mice. C7 was tested in a pharmacological AD mouse model induced by Aβ_1-42 and attenuated memory deficits at doses as low as 5 mg/kg. The pseudo-irreversible cholinesterase inhibitory properties and multifunctional therapeutic attributes of C7 render it a promising candidate for further investigation in the treatment of AD.

2024-01-01·JAMA Pediatrics

High-Dose Docosahexaenoic Acid in Newborns Born at Less Than 29 Weeks’ Gestation and Behavior at Age 5 Years

Article

作者: Sharp, Mary ; Bolisetty, Srinivas ; Opie, Gillian ; Doyle, Lex W ; Anderson, Peter J ; Collins, Carmel T ; Bednarz, Jana M ; Lui, Kei ; Travadi, Javeed ; Cheong, Jeanie L Y ; Stack, Jacqueline ; Roberts, Rachel M ; McPhee, Andrew J ; Makrides, Maria ; Sullivan, Thomas R ; Gibson, Robert A ; Tan, Kenneth ; Best, Karen P ; Liley, Helen ; Simmer, Karen ; Gould, Jacqueline F ; Davis, Peter G ; Morris, Scott

Importance:

Children born at less than 29 weeks’ gestation are at risk of behavioral difficulties. This may be due in part to the lack of transplacental supply of docosahexaenoic acid (DHA), a key fatty acid with structural and functional roles in the brain.

Objective:

To determine whether meeting the neonatal DHA requirement through supplementation is associated with improved behavioral functioning of children born at less than 29 weeks’ gestation.

Design, Setting and Participants:

This was a follow-up of children from 10 Australian participating centers in a multi-center, blinded, parallel group randomized clinical trial of infants born at less than 29 weeks’ gestation conducted from June 2012 and September 2015, excluding those with additional fatty acid supplementation or major congenital or chromosomal abnormalities. Follow-up took place from August 2018 to May 2021. Parents of surviving children who had not withdrawn from the original trial were invited to complete questionnaires when the child turned 5 years’ corrected age.

Interventions:

Infants were randomized to receive daily enteral emulsions providing 60 mg/kg/d of DHA or a soy-oil emulsion (with no DHA) from within the first 3 days of enteral feeding until 36 weeks’ postmenstrual age or discharge home, whichever occurred first.

Main Outcomes and Measures:

The primary outcome of this follow-up was parent-rated behavior and emotional functioning as indicated by the Total Difficulties score of the Strengths and Difficulties Questionnaire. Parents also completed questionnaires about their child’s behavioral manifestations of executive functioning, as well as a range of health outcomes to assess potential longer-term side effects of DHA intervention.

Results:

Primary outcome data were available for 731 children (76% of 958 surviving eligible children; 361 in the intervention group and 370 in the control group). Of these 731, 452 (47%) were female, and the mean (SD) corrected age at follow-up was 5.4 (0.5) years. Following imputation for missing data, the mean Total Difficulties score was the same in both groups (intervention group, n = 465; mean [SD], 11.8 [6.3]; control group, n = 493; mean [SD], 11.8 [6.0]; mean difference adjusted for sex, gestational age stratum, and hospital, 0.01; 95% CI, −0.87 to 0.89; P = .98). There was no evidence for differences between the groups in any secondary outcomes of behavior, executive functioning, or health.

Conclusions and Relevance:

In this follow-up of a randomized clinical trial, enteral DHA supplementation at the equivalent of the estimated in utero dose for infants born at less than 29 weeks’ gestation did not improve behavioral functioning at age 5 years. There were no indications of adverse effects with DHA supplementation.

Trial Registration:

Australian New Zealand Clinical Trial Registry: ACTRN12612000503820

项与三庚酸甘油酯相关的新闻（医药）

2024-05-02

·GlobeNewswire-Health Care

Ultragenyx Reports First Quarter 2024 Financial Results and Corporate Update

First quarter total revenue of $109 million, Crysvita® revenue of $83 million and Dojolvi® revenue of $16 million Reaffirmed 2024 expected total revenue guidance between $500 million to $530 million, Crysvita revenue of $375 million to $400 million, and Dojolvi revenue of $75 million to $80 million Presented positive interim Phase 1/2 data from GTX-102 Angelman syndrome study demonstrating that Expansion Cohorts showed rapid, clinically meaningful improvement across multiple domains consistent with or exceeding Dose-escalation Cohort data at Day 170 NOVATO, Calif., May 02, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, today reported its financial results for the quarter ended March 31, 2024 and reaffirmed its financial guidance for 2024. “In the first quarter we continued to see rapid revenue growth in the international markets with steady progress globally across our four commercial products. We also just completed enrollment of our Phase 3 program in osteogenesis imperfecta supported by strong enthusiasm from treating physicians and the patient community,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “Last month we shared new data from the GTX-102 program for Angelman syndrome and have received an overwhelming response of excitement and support from the clinical experts and advocates in the Angelman community. We are on track to hold regulatory discussions in mid-2024 with the goal of initiating a Phase 3 trial before the end of the year.” First Quarter 2024 Selected Financial Data Tables and Financial Results Revenues (dollars in thousands), (unaudited) Three Months Ended March 31, 2024 2023Crysvita Product sales$36,241 $21,234Revenue in Profit-Share Territory 40,402 49,906Royalty revenue in European Territory 5,942 4,882Total Crysvita Revenue 82,585 76,022Dojolvi 16,362 14,303Mepsevii 6,611 8,480Evkeeza 3,275 212Daiichi Sankyo — 1,479Total revenues$108,833 $100,496 Total RevenuesUltragenyx reported $109 million in total revenue for the first quarter of 2024, which represents 8% growth compared to the same period in 2023. First quarter 2024 Crysvita revenue was $83 million, which represents 9% growth compared to the same period in 2023. This includes product sales of $36 million from Latin America and Turkey, which represents 71% growth compared to the same period in 2023. In April 2023, commercialization responsibilities in the Profit-share Territory transitioned to Kyowa Kirin Co and commensurately, revenue in that region transitioned from a profit-share to a royalty ranging from the mid-20’s to 30% calculated based on annual revenue tiers. Dojolvi revenue in the first quarter 2024 was $16 million, which represents 14% growth compared to the same period in 2023. Selected Financial Data (dollars in thousands, except per share amounts), (unaudited) Three Months Ended March 31, 2024 2023 Total revenues$108,833 $100,496 Operating expenses: Cost of sales 17,533 12,257 Research and development 178,487 165,698 Selling, general and administrative 78,160 76,646 Total operating expenses 274,180 254,601 Net loss$(170,684) $(163,972)Net loss per share, basic and diluted$(2.03) $(2.33) Operating Expenses Total operating expenses for the first quarter of 2024 were $274 million, including non-cash stock-based compensation of $37 million. In 2024, annual operating expenses are expected to be stable or to decrease as the company continues to manage its costs and focus its investment on advancing multiple Phase 3 programs and executing on commercial product launches. Net Loss For the first quarter of 2024, Ultragenyx reported net loss of $171 million, or $2.03 per share basic and diluted, compared with a net loss for the first quarter of 2023 of $164 million, or $2.33 per share, basic and diluted. Net Cash Used in Operations and Cash BalanceNet cash used in operations for the quarter ended March 31, 2024 was $191 million. Cash, cash equivalents, and marketable debt securities were $569 million as of March 31, 2024. 2024 Financial Guidance For the full year 2024, the company reaffirms: Total revenue in the range of $500 million to $530 millionCrysvita revenue in the range of $375 million to $400 million. This includes all regions where Ultragenyx will recognize revenue: product sales in Latin America and Turkey, royalties in Europe, which have been ongoing, and royalties in North America, which began in April 2023.Dojolvi revenue in the range of $75 million to $80 millionNet Cash Used in Operations to be less than $400 million Recent Updates and Clinical Milestones UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Enrollment complete for Phase 3 Orbit and Cosmic studies; expect additional Phase 2 data update in second half of 2024 The Phase 3 portion of the Orbit study has completed enrollment with 158 patients. Orbit is a randomized placebo-controlled study evaluating the effect of setrusumab compared to placebo on the rate of annualized clinical fractures in patients aged 5 to <25 years. Additional longer-term safety and efficacy data from the Phase 2 portion of the Orbit study are expected in the second half of 2024. The Phase 3 Cosmic study has also completed enrollment with 66 patients randomized or in screening. Cosmic is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients aged 2 to <7 years. GTX-102 antisense oligonucleotide for Angelman syndrome: Positive interim Phase 1/2 data shared in April; expect End of Phase 2 meeting with Food and Drug Administration (FDA) in mid-2024New interim data from the Phase 1/2 study were presented at a company presentation and at the 76th Annual American Academy of Neurology Meeting. Patients in Expansion Cohorts A & B treated with a set dose and regimen of GTX-102 showed rapid and clinically meaningful improvement across multiple domains consistent with or exceeding Dose Escalation Cohorts 4-7 data at Day 170. Treatment of the Dose Escalation Cohorts 4-7 showed long-term increasing and sustained clinical benefit far exceeding Natural History data at Day 758. As previously reported and as of the data cut-off on April 5, 2024, there were two patients who had mild or moderate lower extremity weakness across 53 patients who completed the loading phase in the Expansion Cohorts A-E. Both were in Cohorts A & B and none reported in Cohorts C–E. The lower extremity weakness resolved rapidly without sequelae and patients remain in the study without ongoing safety concerns and are expected to continue dosing. The FDA and other regulatory agencies were notified and raised no issues nor required additional actions. There were no other unexpected serious adverse events. We expect to share additional long-term safety and efficacy data from the Phase 1/2 study and plan to continue to provide routine safety updates with efficacy updates. We currently expect to have an End of Phase 2 meeting with the FDA in mid-2024 and meetings with other regulatory agencies in the second half of 2024. UX701 AAV gene therapy for Wilson disease: Last patient in Cohort 3 dosed; expect interim Stage 1 data in the second half of 2024All patients in the three dose-escalation cohorts of Stage 1 have been dosed. During Stage 1, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2, the pivotal, randomized, placebo-controlled stage of the study. Data from Stage 1 are expected in the second half of 2024, which will be followed by dose selection and initiation of Stage 2. UX111 AAV gene therapy for Sanfilippo syndrome (MPS IIIA): Discussions ongoing with FDA, seeking accelerated approval pathIn February 2024, Ultragenyx participated in a workshop hosted by the Reagan-Udall Foundation for the FDA that brought together FDA representatives, patient advocates, scientists, and industry leaders to discuss the use of CSF heparan sulfate as a relevant biomarker to enable accelerated approval in neuronopathic mucopolysaccharidoses (MPS). Discussions are ongoing with the FDA in seeking an accelerated review path for UX111. DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study complete; expect Phase 3 data readout in the second quarter of 2024In May 2023, Ultragenyx announced the last patient was dosed in the Phase 3 study. The 48-week study enrolled 49 patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 safety and efficacy data are expected in the second quarter of 2024. DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients; expect enrollment to be completed in the second half of 2024Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the second half of 2024. Conference Call and Webcast Information Ultragenyx will host a conference call today, Thursday, May 2, 2024, at 2 p.m. PT/5 p.m. ET to discuss the first quarter 2024 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations. To participate in the live call, please register by clicking on the following link (https://register.vevent.com/register/BI7c62f78f6df84941acb020e8220f4d81) and you will be provided with dial-in details. The replay of the call will be available for one year. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare 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: www.ultragenyx.com. 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, and the components and timing of regulatory submissions 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 our clinical development programs, 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 commercial supply of Crysvita, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, the transition back to Kyowa Kirin of our exclusive rights to promote Crysvita in the United States and Canada and unexpected costs, delays, difficulties or adverse impact to revenue related to such transition, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, 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 candidates. 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 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 21, 2024, 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 (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/mycompany/). Contacts Ultragenyx Pharmaceutical Inc.InvestorsJoshua Higair@ultragenyx.com Ultragenyx Pharmaceutical Inc.Selected Statement of Operations Financial Data(in thousands, except share and per share amounts)(unaudited) Three Months Ended March 31, 2024 2023 Statement of Operations Data: Revenues: Product sales$62,489 $44,229 Royalty revenue 46,344 4,882 Collaboration and license — 51,385 Total revenues 108,833 100,496 Operating expenses: Cost of sales 17,533 12,257 Research and development 178,487 165,698 Selling, general and administrative 78,160 76,646 Total operating expenses 274,180 254,601 Loss from operations (165,347) (154,105)Change in fair value of equity investments 3,746 (334)Non-cash interest expense on liabilities for sales of future royalties (15,847) (15,636)Other income, net 7,219 6,598 Loss before income taxes (170,229) (163,477)Provision for income taxes (455) (495)Net loss$(170,684) $(163,972)Net loss per share, basic and diluted$(2.03) $(2.33)Shares used in computing net loss per share, basic and diluted 84,286,292 70,368,478 Ultragenyx Pharmaceutical Inc.Selected Activity included in Operating Expenses(in thousands)(unaudited) Three Months Ended March 31, 2024 2023 Non-cash stock-based compensation$36,934 $31,939 Ultragenyx Pharmaceutical Inc.Selected Balance Sheet Financial Data(in thousands)(unaudited) March 31, December 31, 2024 2023Balance Sheet Data: Cash, cash equivalents, and marketable debt securities $568,661 $777,110Working capital 350,392 451,747Total assets 1,307,080 1,491,013Total stockholders' equity 140,264 275,414

临床3期临床结果财报临床2期

2024-03-27

·药融圈

一文知悉罕见病巨头Ultragenyx管线进展与布局

5月30-31日第八届广州生物医药创新者峰会扫码立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。近年来，罕见病是药企乃至整个社会都很关心的话题。罕见病通常指发病率极低的疾病，又称“孤儿病”。世界各国根据各自实际情况，在罕见病的定义上略有不同。美国将罕见病定义为患者少于20万人/年或其治疗药物销售额预期难以收回研发成本的疾病；欧盟将患病率小于0.5‰、能导致衰弱或威胁生命的疾病定义为罕见病；日本将患者少于 5万/年或患病率小于0.5‰作为罕见病定义标准。我国在2021年《中国罕见病定义研究报告 2021》中将罕见病定义为“新生儿发病率小于1/万、患病率小于1/万且患病人数小于14万的疾病”。其中，80%的罕见病是由遗传缺陷或基因突变造成的，而细胞与基因疗法也正成为罕见病药物研发的热点：相对于常见疾病，罕见病通常由单个基因突变引起，是基因治疗的理想靶标；约有超过90%的罕见病目前缺乏有效治疗药物，基因和细胞治疗作为一种潜在的创新方法，有望为罕见病治疗带来突破性改善。细胞与基因疗法在治疗罕见病方面已展现出重大进展，有望为全球2.6-4.5亿受罕见病影响的人群（包括儿童）带来治愈希望。今天药融圈要介绍的这家公司叫Ultragenyx，它的产品和研发管线均是罕见病药物。Ultragenyx Pharmaceutical（纳斯达克股票代码：RARE）于2010年在硅谷成立，是一家专注于罕见病药物研发与商业化美国生物技术公司。经过2轮融资后，于2014年成功在纳斯达克上市。（截至2024年3月8日，该公司股价50.53美元/股，市值约41.6亿美元。3月26日，市值为37.43亿美元。）其创始人、总裁兼首席执行官Emil Kakkis曾在Harbour-UCLA医疗中心工作，并开发一种针对罕见疾病MPS I 的酶替代疗法。目前，Ultragenyx公司拥有一支在罕见病治疗开发和商业化方面经验丰富的管理团队，在团队的努力下，公司已有4款产品上市，且建立起了一个多元化的候选疗法管线，旨在解决未被满足的医疗需求。其中，Crysvita被批准用于治疗X连锁低磷血症（XLH），以及肿瘤性低磷骨软化症（TIO）。管线布局&产品Ultragenyx目前批准的疗法和临床阶段的产品线包括四个产品类别：生物制剂、小分子、AAV基因疗法和核酸候选药物，有四种已获商业上市批准的产品：用于治疗X-连锁低磷血症（XLH）和肿瘤诱导的骨软化症（TiO）的Crysvita®（burosumab）、用于儿童和成年人黏多糖贮积症VII型（MPSVII）或SLY综合征的Mepsevii®（vestronidase Alfa）、用于治疗长链脂肪酸氧化障碍（LC-FAOD）的Dojolvi®（triheptanoin）和用于治疗家族性高胆固醇血症（HoFH）的Evkeeza®（evinacumab）。上市产品1.Crysvita®（burosumab/布罗索尤单抗）CRYSVITA于2018年4月在美国获批上市。CRYSVITA是成纤维细胞生长因子23 (fibroblast growth factor23, FGF23)的阻断抗体。当时获批的适应症是6个月以上的儿童及成人X连锁低磷酸盐血症(X-linked hypophosphatemia, XLH, 又名：家族性低磷酸血症佝偻病)。XLH是一种罕见的、遗传性的、进行性的和终生的骨骼肌肉系统疾病。其病因是体内调磷因子FGF23产生过多或降解障碍，使循环中FGF23水平增加，导致肾脏排磷增多及低磷血症。估计所有的发达国家中有约48,000个病人，包含约36,000成人和12,000儿童。在2020年6月，FDA批准了CRYSVITA的第2个适应症：2岁及以上的儿童及成人肿瘤性骨软化症的低磷酸盐血症(FGF23相关)。肿瘤性骨软化症通常是由产生过量FGF23的良性肿瘤所引起的，该病将会导致严重的低磷酸盐血症、骨折以及肌无力。一般首选的治疗方案是手术切除肿瘤，但对于某些患者，肿瘤无法切除或肿瘤切除后复发。对于这些患者仍然存在着巨大的未满足临床需求。估计所有的发达国家肿瘤性骨软化症的患者数量约为2,000-4,000。除了在美国，目前CRYSVITA还在加拿大，欧洲地区(欧盟、英国、瑞士等)，南美，土耳其等地获批。Ultragenyx正在与日本巨头协和麒麟/Kyowa Kirin Co.，Ltd.（简称KKC）以及KKC的全资子公司Kyowa Kirin合作，在全球范围内开发和商业化Crysvita。中国也已经获批上市。2.Mepsevii®（vestronidase Alfa）MEPSEVII于2017年11月在美国获批上市。该药是一种重组人溶酶体β葡萄糖醛酸酶(酶替代疗法)，用于儿童和成年人黏多糖贮积症VII型(MPS VII，斯莱综合征【Sly syndrome】)的治疗。黏多糖贮积症(mucopolysaccharidosis，MPS)是一组复杂的、进行性多系统受累的溶酶体病，是由于降解糖胺聚糖的酶缺乏所致。黏多糖贮积症共分为7型。黏多糖贮积症VII型是最罕见的溶酶体贮积症亚型之一，估计所有的发达国家中只有约200个病人，国内目前仍然缺乏大样本流行病学数据。VII型通常会导致多器官功能衰竭，广泛性骨骼功能障碍和死亡。除了在美国，目前MEPSEVII还在欧盟、英国，巴西和墨西哥获批。3.Dojolvi®（triheptanoin）Dojolvi于2020年6月在美国获批上市。该药是一种高纯度的、合成的7碳脂肪酸甘油三酯。它是一种中链、奇数碳脂肪酸，可作为能量来源及体内各反应的代谢产物的替代品，用来治疗儿童和成人长链脂肪酸氧化障碍(Long-chain fatty acid oxidation disorders, LC-FAOD) 。LC-FAOD是一组罕见的代谢性疾病，该病会抑制脂肪代谢，阻止脂肪转化为能量，并可能导致低血糖、肌肉撕裂、心脏以及肝脏疾病。估计所有的发达国家中有约8,000-14,000个病人。4.Evkeeza®（evinacumab）药融云数据（www.pharnexcloud.com）显示：Evkeeza是一种通过静脉注射给药的全人单克隆抗体，可结合并阻断血管生成素样蛋白3（ANGPTL3）的功能，ANGPTL3是一种在脂质代谢中起关键作用的蛋白质，用于治疗纯合子家族性高胆固醇血症（HoFH）。Evinacumab是Evkeeza中的活性成分，它能结合到体内的一种名为ANGPTL3的蛋白，并阻断其作用。ANGPTL3涉及控制胆固醇水平，阻断其作用可降低血液中的胆固醇水平。Evkeeza通过每月（4周）一次的输注给药。本品为与再生元联合开发。（关联阅读：再生元进击千亿美金俱乐部，减重领域或将续写传奇）药融云数据，www.pharnexcloud.comHoFH是一种极为罕见的遗传性疾病，是家族性高胆固醇血症（FH）中最严重的一种。Evkeeza是美国和欧盟批准的首个ANGPTI-3靶向疗法，用于辅助治疗12岁及以上HoFH患者。目前，Evkeeza正被评估用于5-11岁HoFH患者。在美国以外的发达国家，大约有3，000到5，000名HoFH患者。据估计，每100万人中约有4人患有HoFH，而且由于患者稀少，Evkeeza的治疗成本巨大，平均每年约45万美元。管线更新和临床里程碑1. UX143（Setrusumab）单克隆抗体治疗成骨不全症（OI）：ORBIT研究的3期部分预计将于2024年第一季度末全部纳入在后期临床试验Orbit和Cosmic中，患者正在接受给药，这些试验正在评估setrusumab在儿童和年轻成人OI患者中的应用。ORBIT研究的随机、安慰剂对照3期部分预计将招募约150名患者，并于2024年第一季度末全部招募。ORBIT研究的其他长期2期安全性和有效性数据预计将于2024年下半年公布。3期COSMIC研究是一项活性对照研究，旨在评估setrusumab与静脉注射双膦酸盐（IV-BP）治疗相比，对2至5岁以下患者的年度总骨折率的影响。Cosmic预计将在全球20多个地点招募约50名或更多患者，预计将于2024年上半年完成招募。2. GTX-102反义寡核苷酸治疗Angelman综合征:1/2期完全入组；预计2024年上半年的扩张数据扩大队列的招募工作于2023年12月完成，共招募了53名新患者。共有74名患者参加了1/2期研究，包括剂量递增/扩展研究患者。扩展队列将评估许多与先前纳入的剂量递增/扩展队列相同的安全性、药代动力学和疗效指标，以及一些新的评估。下一次安全性和有效性更新预计将于2024年上半年进行，并计划纳入至少20名扩展队列患者的数据，其中至少有170天的数据。2024年1月，GTX-102被欧洲药品管理局（EMA）纳入优先药品（PRIME）计划。PRIME由欧洲药品管理局（EMA）授予那些根据早期临床数据显示有潜力使需求未得到满足的患者受益的药物。通过PRIME，EMA提供早期和主动支持，以优化开发计划，生成有关药物效益和风险的可靠数据，并加快对药物应用的评估。3. UX701 AAV基因治疗Wilson病：队列3中最后一名患者给药；预计中期第一阶段数据将于2024年中期发布第1阶段的三个剂量递增队列中的所有患者均已给药。在第1阶段，将评估UX701的安全性和有效性，并在第2阶段（该研究的关键、随机、安慰剂对照阶段）选择剂量进行进一步评估。第一阶段的数据预计将在2024年中期公布，随后将在2024年下半年进行剂量选择并启动第二阶段。4. UX111 AAV基因治疗Sanfilippo综合征（MPS IIIA）：2024年2月初，该公司在第20届年度世界研讨会（WorldSymposium™）上公布了一项正在进行的关键转移（Pivotal Transfer）研究的新的积极数据，该研究评估了UX111在患有MPS IIIA的儿童中的安全性和有效性，显示单次输注UX111可以显著纠正潜在的代谢疾病，并维持几乎所有患者的认知功能。该报告还显示，观察到的脑脊液中硫酸乙酰肝素暴露的减少可以预测UX111治疗后MPS IIIA患者的长期认知功能的改善。有了这些数据和其他数据，正在与FDA进行讨论，以寻求UX111的加速审查路径。5. DTX401 AAV基因治疗Ia型糖原贮积病（GSDIA）:3期研究完成给药；第3阶段数据读出预计在2024年上半年。2023年5月，Ultragenyx宣布最后一名患者在3期研究中接受了给药。这项为期48周的研究纳入了8岁及以上的患者，按1:1的比例随机分配至DTX401或安慰剂组。3期安全性和有效性数据预计将于2024年上半年公布。DTX301 AAV基因治疗鸟氨酸氨甲酰转移酶（OTC）缺乏症:3期研究给药患者；预计招生工作将于2024年上半年完成在正在进行的3期研究中，Ultragenyx正在对患者进行随机分组和给药。关键的64周研究将包括约50名患者，按1:1随机分配至DTX301或安慰剂组。主要终点是通过去除氨清除剂药物和蛋白质限制饮食以及24小时氨水平的变化来测量的反应。招募工作预计将于2024年上半年完成。财务状况2024年2月22日，Ultragenyx公布2023财年年报。2023年Ultragenyx总营收为4.34亿美元，其中Crysvita收入3.25 ~ 3.3 亿美元；预计公司2024年总营收达到5.3亿美元。截至2023年末，该公司现金、现金等价物和有价债务证券约7.76亿美元。与2022财年相比，2023财年Ultragenyx的产品销售额增加了6150万美元。这一增长主要是由于拉丁美洲对Crysvita的需求增加，原因是接受治疗的患者数量增加，对其他批准产品的需求持续增加，以及指定患者计划的收入增加；Crysvita合作收入和特许权收入净增加了1560万美元。Crysvita收入的增加主要是由于接受治疗的患者数量增加；从Daiichi Sankyo/第一三共中获得的收入减少了620万美元，减少原因是2023年完成了技术转让和技术转让期。下表是按主要项目类型和业务活动划分的研发费用明细（千美元）:与2022财年相比，2023财年Ultragenyx的研发费用总额减少了5730万美元，主要由于：• 对于基因治疗项目，增加1500万美元，主要与2022年5月从Abeona Therapeutics收购的UX111项目的开发成本增加以及内部制造的生产材料采购增加有关，部分被DTX401的外部临床制造费用的减少所抵消；• 对于生物和核酸项目，增加1160万美元，主要与UX143和GTX102项目的持续临床进展以及相关的临床开发和制造费用有关，部分被用于治疗III型糖原贮积病的UX053开发费用的减少所抵消；• 对于转化研究，减少了960万美元，主要与IND阶段项目的制造和员工人数费用减少有关；• 前期许可、收购和里程碑费用减少6600万美元，原因是截至2023年12月31日确认的UX143项目临床登记里程碑的费用为900万美元，而截至2022年12月31日收购Genetx的费用为7500万美元；• 对于批准的产品，减少2220万美元，主要是由于北美的Crysvita商业化责任转移到KKC，以及Dojolvi实现了成本效益，部分抵消了Regeneron协作费用的报销以及Evkeeza人员和产品发布成本的增加；截至2023年12月31日，Ultragenyx拥有7.771亿美元的可用现金、现金等价物和可出售的债务证券，该公司称其现有资产将足以满足至少未来12个月的运营需求。参考：NMPA/CDE；药融云数据，www.pharnexcloud.com；FDA/EMA/PMDA；相关公司公开披露；https://www.ultragenyx.com/；https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-reports-fourth-quarter-and-full-year-2023-financial；https://www.sec.gov/Archives/edgar/data/1515673/000095017024017879/rare-20231231.htm；https://mp.weixin.qq.com/s/-2XHmyVS_hIOqNfvFBzoGQ；https://www.sec.gov/Archives/edgar/data/1515673/000119312523259557/d542322d424b5.htm；https://mp.weixin.qq.com/s/V8pzc7DjO7oqn2mmm9PPdw；等等。本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐活动推荐 8月 • NDC2024生物医药创新博览会关键词：抗体、多肽、核酸、核药，XDC、小分子、注册、临床、CMC（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

基因疗法上市批准孤儿药核酸药物

2024-02-15

·GlobeNewswire-Health Care

Ultragenyx Reports Fourth Quarter and Full Year 2023 Financial Results and Corporate Update

2023 Total Revenue of $434 million, Crysvita® revenue of $328 million and Dojolvi® revenue of $71 million 2024 Financial Guidance: Total Revenue between $500 million and $530 million, Crysvita revenue of $375 million to $400 million, and Dojolvi revenue of $75 million to $80 million Year-end 2023 cash balance of $777 million and 2024 guidance for Net Cash Used in Operations expected to be less than $400 million NOVATO, Calif., Feb. 15, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, today reported its financial results for the quarter and full year ended December 31, 2023 and reaffirmed its financial guidance for 2024. “Last year, we made significant progress across our pipeline and look forward to multiple catalysts in 2024 with substantive data in Angelman syndrome that could enable a Phase 3 study, pivotal Phase 3 data from our GSDIa gene therapy program, dose-finding data from our seamless study in Wilson disease, and longer-term Phase 2 data in Osteogenesis Imperfecta,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “In 2023, we saw increased demand for both Crysvita and Dojolvi, and achieved multiple regulatory and reimbursement milestones for our commercial products to support continued revenue growth of approximately 20% in 2024.” Fourth Quarter and Full Year 2023 Selected Financial Data Tables and Financial Results Revenues (dollars in thousands), (unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022Crysvita Product sales$18,379 $7,698 $75,697 $42,678Revenue in Profit-Share Territory 70,124 66,903 231,574 215,024Royalty revenue in European Territory 5,612 6,058 20,783 21,692Total Crysvita Revenue 94,115 80,659 328,054 279,394Dojolvi 23,286 16,412 70,633 55,612Mepsevii 7,889 4,798 30,441 20,637Evkeeza 2,102 — 3,642 —Daiichi Sankyo — 1,479 1,479 7,686Total revenues$127,392 $103,348 $434,249 $363,329 Total RevenuesUltragenyx reported $127 million in total revenue for the fourth quarter 2023, which represents 23% growth compared to the same period in 2022. Fourth quarter 2023 Crysvita revenue was $94 million, which represents 17% growth compared to the same period in 2022. This includes product sales of $18 million from Latin America and Turkey, which represents 139% growth compared to the same period in 2022. Dojolvi revenue in the fourth quarter 2023 was $23 million, which represents 42% growth compared to the same period in 2022. Total revenue for the year ended December 31, 2023 was $434 million, which represents 20% growth compared to the prior year. Full year 2023 Crysvita revenue was $328 million, which represents 17% growth compared to the same period in 2022. This includes product sales of $76 million from Latin America and Turkey, which represents 77% growth compared to the same period in 2022. Dojolvi revenue in 2023 was $71 million, which represents 27% growth compared to the same period in 2022. Selected Financial Data (dollars in thousands, except per share amounts), (unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Total revenues$127,392 $103,348 $434,249 $363,329 Operating expenses: Cost of sales 12,051 5,319 45,209 28,320 Research and development 160,557 170,808 648,449 705,789 Selling, general and administrative 76,833 72,849 309,799 278,139 Total operating expenses 249,441 248,976 1,003,457 1,012,248 Net loss$(123,190) $(151,833) $(606,639) $(707,421)Net loss per share, basic and diluted$(1.52) $(2.16) $(8.25) $(10.12) Operating Expenses Total operating expenses for the fourth quarter of 2023 were $249 million, including non-cash stock-based compensation of $34 million. Total operating expenses for the year ended December 31, 2023 were $1,003 million, including $135 million of non-cash stock-based compensation. In 2024, annual operating expenses are expected to be stable or to decrease as the company continues to manage its costs, focus its investment on advancing multiple Phase 3 programs, and execute on commercial product launches. Net Loss For the fourth quarter of 2023, Ultragenyx reported net loss of $123 million, or $1.52 per share basic and diluted, compared with a net loss for the fourth quarter of 2022 of $152 million, or $2.16 per share, basic and diluted. For the year ended December 31, 2023, Ultragenyx reported net loss of $607 million, or $8.25 per share basic and diluted, compared with a net loss the prior year of $707 million, or $10.12 per share, basic and diluted. Net Cash Used in Operations and Cash BalanceNet cash used in operations for the year ended December 31, 2023 was $475 million. Cash, cash equivalents, and marketable debt securities were $777 million as of December 31, 2023. 2024 Financial Guidance For the full year 2024, the company reaffirms: Total revenue in the range of $500 million to $530 millionCrysvita revenue in the range of $375 million to $400 million. This includes all regions where Ultragenyx will recognize revenue: product sales in Latin America and Turkey, royalties in Europe, which have been ongoing, and royalties in North America, which began in April 2023.Dojolvi revenue in the range of $75 million to $80 millionNet Cash Used in Operations to be less than $400 million Recent Updates and Clinical Milestones UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Phase 3 portion of Orbit study expected to be fully enrolled around the end of the first quarter of 2024Patients are being dosed in the late-stage clinical trials, Orbit and Cosmic, which are evaluating setrusumab in pediatric and young adult patients with OI. The randomized, placebo-controlled Phase 3 portion of the Orbit study is expected to enroll approximately 150 patients and be fully enrolled around the end of the first quarter of 2024. Additional longer-term Phase 2 safety and efficacy data from the Orbit study are expected in the second half of 2024. The Phase 3 Cosmic study is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients age 2 to <5 years. Cosmic is expected to enroll approximately 50 patients or more at more than 20 global sites and is expected to complete enrollment in the first half of 2024. GTX-102 antisense oligonucleotide for Angelman syndrome: Phase 1/2 fully enrolled; expansion data expected in the first half of 2024Enrollment in the expansion cohorts was completed in December 2023 with a total of 53 new patients enrolled. A total of 74 patients are enrolled in the Phase 1/2 study including the dose-escalation/extension study patients. The expansion cohorts will evaluate many of the same safety, pharmacokinetic, and efficacy measures as the previously enrolled dose-escalation/extension cohorts plus some new evaluations. The next safety and efficacy update is expected in the first half of 2024 and is planned to include data from at least 20 expansion cohort patients with a minimum of Day 170 data. In January 2024, GTX-102 was accepted into the Priority Medicines (PRIME) program by the European Medicines Agency (EMA). PRIME is granted by the EMA to medicines that show the potential to benefit patients with unmet needs based on early clinical data. Through PRIME, the EMA offers early and proactive support to optimize development plans and the generation of robust data on a medicine’s benefits and risks, and enables accelerated assessment of medicines applications. UX701 AAV gene therapy for Wilson disease: Last patient in Cohort 3 dosed; expect interim Stage 1 data in mid-2024All patients in the three dose-escalation cohorts of Stage 1 have been dosed. During Stage 1, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2, the pivotal, randomized, placebo-controlled stage of the study. Data from Stage 1 are expected in mid-2024, which will be followed by dose selection and initiation of Stage 2 in the second half of 2024. UX111 AAV gene therapy for Sanfilippo syndrome (MPS IIIA): Updated data from pivotal Transfer A study presented at WORLDSymposiumTM New positive data from the ongoing pivotal Transfer A study evaluating the safety and efficacy of UX111 in children with MPS IIIA were presented at the 20th Annual WORLDSymposium™ earlier this month showing that a single infusion of UX111 can substantially correct the underlying metabolic disease and maintain cognitive function in nearly all patients. The presentation also showed that the observed reductions of heparan sulfate exposure in cerebrospinal fluid can predict improved long-term cognitive function in patients with MPS IIIA following treatment with UX111. With these data and other data, discussions are ongoing with the FDA seeking an accelerated review path for UX111. DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study complete; Phase 3 data readout expected in the first half of 2024In May 2023, Ultragenyx announced the last patient had been dosed in the Phase 3 study. The 48-week study has fully enrolled patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 safety and efficacy data are expected in the first half of 2024. DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients; expect enrollment to be completed in the first half of 2024Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the first half of 2024. Conference Call and Webcast Information Ultragenyx will host a conference call today, Thursday, February 15, 2024, at 2 p.m. PT/5 p.m. ET to discuss the fourth quarter and full year 2023 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations. To participate in the live call, please register by clicking on the following link (https://register.vevent.com/register/BI177d5c166d3045ddaa4dcd3b3ec136ba) and you will be provided with dial-in details. The replay of the call will be available for one year. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare 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: www.ultragenyx.com. 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, and the components and timing of regulatory submissions 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 our clinical development programs, 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 commercial supply of Crysvita, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, the transition back to Kyowa Kirin of our exclusive rights to promote Crysvita in the United States and Canada and unexpected costs, delays, difficulties or adverse impact to revenue related to such transition, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, 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 candidates. 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 3, 2023, 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 (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/mycompany/). Contacts Ultragenyx Pharmaceutical Inc.InvestorsJoshua Higair@ultragenyx.com Ultragenyx Pharmaceutical Inc.Selected Statement of Operations Financial Data(in thousands, except share and per share amounts)(unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Statement of Operations Data: Revenues: Product sales$51,656 $28,908 $180,413 $118,927 Royalty revenue 75,736 6,058 182,652 21,692 Collaboration and license — 68,382 71,184 222,710 Total revenues 127,392 103,348 434,249 363,329 Operating expenses: Cost of sales 12,051 5,319 45,209 28,320 Research and development 160,557 170,808 648,449 705,789 Selling, general and administrative 76,833 72,849 309,799 278,139 Total operating expenses 249,441 248,976 1,003,457 1,012,248 Loss from operations (122,049) (145,628) (569,208) (648,919)Change in fair value of equity investments 1,889 1,840 397 (19,299)Non-cash interest expense on liabilities for sales of future royalties (17,328) (15,874) (66,004) (43,015)Other income, net 10,596 6,378 26,351 9,508 Loss before income taxes (126,892) (153,284) (608,464) (701,725)Benefit from (provision for) income taxes 3,702 1,451 1,825 (5,696)Net loss$(123,190) $(151,833) $(606,639) $(707,421)Net loss per share, basic and diluted$(1.52) $(2.16) $(8.25) $(10.12)Shares used in computing net loss per share, basic and diluted 81,118,873 70,152,192 73,543,862 69,914,225 Ultragenyx Pharmaceutical Inc.Selected Activity included in Operating Expenses(in thousands)(unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Non-cash stock based compensation$33,744 $29,355 $135,213 $130,368In-process research and development expense from GeneTx acquisition — $(201) — $75,033UX143 clinical milestone — — $9,000 — Ultragenyx Pharmaceutical Inc.Selected Balance Sheet Financial Data(in thousands)(unaudited) December 31, December 31, 2023 2022Balance Sheet Data: Cash, cash equivalents, and marketable debt securities $777,110 $896,732Working capital 451,747 622,689Total assets 1,491,013 1,545,444Total stockholders' equity 275,414 352,494

临床3期财报基因疗法

100 项与三庚酸甘油酯相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11465	三庚酸甘油酯	A	DB11677

研发状态

适应症	最高研发状态	国家/地区	公司
脂肪酸氧化代谢病	批准上市	美国更多	Ultragenyx Pharmaceutical, Inc. 更多
Glut1缺陷综合征	终止	英国更多	Ultragenyx Pharmaceutical, Inc. 更多
神经运动障碍	终止	美国更多	Ultragenyx Pharmaceutical, Inc. 更多
伴肌病和神经病的三功能蛋白缺乏症	无进展	英国更多	Ultragenyx Pharmaceutical, Inc. 更多
亨廷顿舞蹈病	无进展	荷兰更多	Ultragenyx Pharmaceutical, Inc. 更多

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03041363 (Pubmed)	临床1期	Glut1缺陷综合征	12	Triheptanoin 1g/Kg/day	憲鏇鏇積鹽觸積鬱壓淵(壓範製獵積淵製鏇顧範) = One dose-limiting toxicity, occurring in 1 of 6 subjects, was encountered in the middle age group in the context of frequently reduced gastrointestinal tolerance for all groups 鹹夢築壓範鑰廠鹹蓋築 (選範淵積構鏇憲蓋構積 ) 更多	-	2023-03-01
NCT02214160 (CTgov)	临床2期	肉毒碱棕榈酰转移酶缺乏症 \| 肉碱酰基肉碱转位酶缺乏症 \| 伴肌病和神经病的三功能蛋白缺乏症 ... 更多	94	UX007 (UX007-CL201-Rollover Cohort)	襯鹽願製製鹹膚繭簾鏇(鏇齋壓鏇網壓醖膚顧壓) = 鬱窪窪壓繭窪願憲廠獵餘網鹹膚網衊鹹鬱觸構 (襯築積構膚衊網醖襯鹹, 淵衊觸鏇鑰憲壓襯艱齋 ~ 艱蓋夢製淵餘廠觸齋遞) 更多	-	2021-12-08
NCT02214160 (CTgov)	临床2期	肉毒碱棕榈酰转移酶缺乏症 \| 肉碱酰基肉碱转位酶缺乏症 \| 伴肌病和神经病的三功能蛋白缺乏症 ... 更多	94	triheptanoin (IST/Other Cohort)	齋醖築鹹蓋鹽糧顧憲網(夢糧鹹廠顧齋衊糧顧鹹) = 願衊築鏇壓願夢衊願艱醖醖齋廠鬱鹹製製齋鏇 (鑰製觸遞遞鑰鬱憲齋夢, 窪膚糧鏇壓醖醖襯鬱窪 ~ 衊鬱鑰鬱襯膚餘襯醖餘) 更多	-	2021-12-08
NCT01886378 (CTgov)	临床2期	肉碱棕榈酰转移酶2缺乏症 \| 伴肌病和神经病的三功能蛋白缺乏症 \| 脂肪酸氧化代谢病 ... 更多	29	UX007	簾構糧繭選蓋網衊顧範(願壓膚鹹築鹹膚簾簾醖) = 願選獵製鹹窪製製鹹壓膚餘範襯繭廠構壓壓壓 (鑰鹹顧窪願網鏇範鬱鹹, 齋壓鹽鹽遞簾襯構選積 ~ 壓鏇鏇憲積願齋膚簾夢) 更多	-	2021-02-11
NCT02036853 (CTgov)	临床2期	Glut1缺陷综合征	20	Triheptanoin (Schedule A)	蓋衊糧餘遞廠窪鏇鏇獵(齋蓋範鏇繭鏇醖製製範) = 糧願範襯餘夢簾夢壓顧觸鹽鹹製遞糧襯遞壓醖 (積襯範鑰顧鹽製襯觸製, 鑰蓋願廠願範觸鑰鬱鏇 ~ 襯襯淵窪窪鹽鏇蓋齋蓋) 更多	-	2021-01-28
NCT02036853 (CTgov)	临床2期	Glut1缺陷综合征	20	Triheptanoin (Schedule B)	蓋衊糧餘遞廠窪鏇鏇獵(齋蓋範鏇繭鏇醖製製範) = 鏇繭選顧製餘艱網糧願觸鹽鹹製遞糧襯遞壓醖 (積襯範鑰顧鹽製襯觸製, 廠選壓窪壓醖淵觸糧鬱 ~ 遞艱夢廠膚襯簾鬱遞製) 更多	-	2021-01-28
NCT01993186 (CTgov)	临床2期	Glut1缺陷综合征	36	UX007 (UX007)	觸顧選遞淵糧繭構衊膚(選網簾築蓋壓獵製齋艱) = 淵積構築網蓋鏇鹹網鏇觸製網鏇鬱壓壓壓簾夢 (範廠鑰構鑰襯積鏇衊願, 獵蓋醖壓齋獵觸繭積憲 ~ 壓廠餘艱選繭遞築鹹鹽) 更多	-	2020-05-29
NCT01993186 (CTgov)	临床2期	Glut1缺陷综合征	36	placebo (Placebo)	觸顧選遞淵糧繭構衊膚(選網簾築蓋壓獵製齋艱) = 範選顧齋繭醖顧獵鏇艱觸製網鏇鬱壓壓壓簾夢 (範廠鑰構鑰襯積鏇衊願, 襯觸淵鹹齋鑰餘範遞製 ~ 鏇顧製網艱顧夢繭範積) 更多	-	2020-05-29
NCT02599961 (CTgov)	临床2期	Glut1缺陷综合征	15	UX007 (Triheptanoin)	糧繭襯鏇窪製膚鏇願鏇(膚獵膚構觸鬱觸鬱餘獵) = 構築簾範餘繭膚餘齋範築鏇鹽觸糧膚糧淵範蓋 (醖餘顧製糧築鹽遞淵憲, 廠簾範鹽願獵壓糧憲齋 ~ 網窪廠積襯糧積鹹廠鏇) 更多	-	2020-04-30
NCT02960217 (CTgov)	临床3期	神经运动障碍 \| Glut1缺陷综合征	44	UX007 (Double-Blind UX007)	夢構構願顧蓋窪鏇鏇遞(膚鬱蓋鏇鑰鹹壓餘顧餘) = 糧範淵衊艱築鏇醖構夢鹹壓膚餘繭構憲鹹範糧 (遞顧築鑰壓鹽齋壓蓋觸, 範鏇簾積鹹鑰醖構觸獵 ~ 鹹遞構遞鏇鬱窪願夢製) 更多	-	2020-04-24
NCT02960217 (CTgov)	临床3期	神经运动障碍 \| Glut1缺陷综合征	44	Placebo (Double-Blind Placebo)	夢構構願顧蓋窪鏇鏇遞(膚鬱蓋鏇鑰鹹壓餘顧餘) = 鏇獵壓願積鹽鏇壓選獵鹹壓膚餘繭構憲鹹範糧 (遞顧築鑰壓鹽齋壓蓋觸, 醖壓鑰築窪醖鬱選顧齋 ~ 醖構築鏇網糧鑰鹽鏇膚) 更多	-	2020-04-24
NCT02679235 (CTgov)	临床1/2期	中叶综合征	15	POST Triheptanoin	膚廠糧蓋壓窪簾積願製(夢構窪選遞鏇夢遞壓蓋) = 醖簾鑰網壓網蓋遞膚窪艱鹹願鏇膚醖繭構繭夢 (壓顧餘獵衊鏇鹹範鑰網, 鬱網鏇憲遞憲觸範鏇窪 ~ 願製簾鹽憲夢選膚餘糧) 更多	-	2020-04-15
NCT02018315 (CTgov)	临床1期	疲劳 \| Glut1缺陷综合征	14	Triheptanoin	觸醖簾衊衊顧範選觸齋(餘觸鏇繭衊蓋鹽糧築鬱) = 夢繭鑰膚醖網壓鑰憲鬱艱鏇淵範鹽醖顧製積窪 (醖獵壓積範衊鏇夢構積, 積鏇夢鬱壓壓鹽製糧繭 ~ 艱築遞夢鹽鏇餘窪繭鬱) 更多	-	2019-10-31
NCT02214160 (SSIEM2019)	临床2期	脂肪酸氧化代谢病	75	Triheptanoin	獵淵鑰積鹹艱艱淵襯鹽(襯製鑰選選簾糧觸餘襯) = abdominal pain/discomfort 顧築窪網築網鏇鹹窪願 (餘遞製製鏇夢築衊膚淵 ) 更多	-	2019-08-25