Refsum Disease, Infantile

Researchers who work with tiny drug carriers known as lipid nanoparticles have developed a new type of material capable of reaching the lungs and the eyes, an important step toward genetic therapy for hereditary conditions like cystic fibrosis and inherited vision loss. Researchers who work with tiny drug carriers known as lipid nanoparticles have developed a new type of material capable of reaching the lungs and the eyes, an important step toward genetic therapy for hereditary conditions like cystic fibrosis and inherited vision loss. Findings of the study led by Gaurav Sahay and Yulia Eygeris of the Oregon State University College of Pharmacy and Renee Ryals of Oregon Health & Science University were published today in the Proceedings of the National Academy of Sciences. Unlike other types of lipid nanoparticles that tend to accumulate in the liver, the ones in this study, based on the compound thiophene, are able to navigate their way to the tissues of the lungs and retina, where they deliver their therapeutic payload. The researchers refer to these new lipids as Thio-lipids. The collaboration demonstrated, by using animal models, the possibility of using Thio-lipids in lipid nanoparticles to deliver messenger RNA, the technology underpinning COVID-19 vaccines, to combat genetic blindness and pulmonary disease. "These nanoparticles filled with fatty lipids can encapsulate genetic medicines like mRNA and CRISPR-Cas9 gene editors, which can be used to treat and even cure rare genetic diseases," said Eygeris, a senior research associate at OSU. "Chemical structures of the lipids determine how potent are the lipid nanoparticles and which organ they can reach from the bloodstream." Lipids are organic compounds containing fatty tails and are found in many natural oils and waxes, and nanoparticles are tiny pieces of material ranging in size from one- to 100-billionths of a meter. Messenger RNA delivers instructions to cells for making a particular protein. With the coronavirus vaccines, the mRNA carried by the lipid nanoparticles instructs cells to make a harmless piece of the virus' spike protein, which triggers an immune response from the body. As a therapy for vision impairment resulting from inherited retinal degeneration, the mRNA would instruct cells in the retina -- which don't work right because of a genetic mutation -- to manufacture the proteins needed for sight. Inherited retinal degeneration, commonly abbreviated to IRD, encompasses a group of disorders of varying severity and prevalence that affect one out of every few thousand people worldwide. An example of a genetic pulmonary condition is cystic fibrosis, a progressive disorder that results in persistent lung infection and affects 30,000 people in the U.S., with about 1,000 new cases identified every year. One faulty gene -- the cystic fibrosis transmembrane conductance regulator, or CFTR -- causes the disease, which is characterized by lung dehydration and mucus buildup that blocks the airway. The thiophene-based lipid nanoparticle study, which involved mice and non-human primates, stems from a $3.2 million grant to Sahay and Ryals from the National Eye Institute. The grant's purpose is addressing limitations associated with the current primary means of delivery for gene editing: a type of virus known as adeno-associated virus, or AAV. "AAV has limited packaging capacity compared to lipid nanoparticles and it can prompt an immune system response," said Sahay, a professor of pharmaceutical sciences. "It also doesn't do fantastically well in continuing to express the enzymes the editing tool uses as molecular scissors to make cuts in the DNA to be edited." Sahay calls the Thio-lipid findings "highly encouraging" but says more studies are needed, including research on the lipids' long-term impact on retinal health. "But we think our results serve as a proof of concept and we will continue to explore Thio-lipids in potential treatments of pulmonary and retinal genetic diseases," he said. In addition to the National Eye Institute, funding and research support were provided by the Oregon National Primate Research Center and the Casey Eye Institute.

The presentation will review study population data from ONL’s Phase 2 study of ONL1204 Ophthalmic Solution in patients with Macula-Off Rhegmatogenous Retinal DetachmentANN ARBOR, Mich., Jan. 23, 2024 (GLOBE NEWSWIRE) -- ONL Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapies for protecting the vision of patients with retinal disease, announced today that David Zacks, M.D., Ph.D., chief scientific officer and co-founder of ONL Therapeutics, and the Edna H. Perkiss Research Professor of Ophthalmology and Visual Sciences at the Kellogg Eye Center of the University of Michigan, will present an update on the company’s Phase 2 study in patients with rhegmatogenous retinal detachment (RRD) at the upcoming 47th Annual Meeting of the Macula Society, being held February 7 – 10, 2024, at the La Quinta Resort & Club in Palm Springs, California. “We believe our Phase 2 randomized study to assess the safety and efficacy of intravitreal ONL1204 Ophthalmic Solution in patients with macula-off rhegmatogenous retinal detachment (RRD) could play an important role in treating this vision-threatening condition, and we look forward to sharing an update at the Macula Society meeting,” said David Esposito, chief executive officer of ONL Therapeutics. “With the study now fully enrolled we will focus our attention on gathering and analyzing the data with a goal to share topline results in the second quarter of 2024.” Details of the podium presentation are as follows: Title: Fas Inhibition with ONL1204 for Macula-off Rhegmatogenous Retinal Detachment (RRD): Study Population Data on a Phase 2, Multicenter, Randomized, Sham-controlled, Single-Masked, Clinical Trial Presenter: David N. Zacks, M.D., Ph.D.Chief Scientific Officer, ONL TherapeuticsEdna H. Perkiss Research Professor of Ophthalmology and Visual Sciences, Kellogg Eye CenterUniversity of Michigan Date / Time: Saturday, February 10, 2024, at 10:28 a.m. PT Session: Surgery I (Retinal Detachment) About Rhegmatogenous Retinal DetachmentRhegmatogenous retinal detachment (RRD) is an acute and serious vision-threatening condition in which a tear in the retina allows liquefied vitreous to enter the subretinal space, thereby detaching the photoreceptor (PR) layer of the retina from the retinal pigment epithelium (RPE), the principal source of metabolic support for the PR layer. Once detached, PRs undergo a cascade of inflammation and cell death leading to vision loss after RRD. There are nearly 100,000 retinal detachment repairs annually in the US alone. About ONL1204 Ophthalmic SolutionONL1204 is a novel, first-in-class small molecule Fas inhibitor designed to protect key retinal cells, including photoreceptors, from cell death that occurs across a range of retinal diseases and conditions. Death of these retinal cells, through both direct and inflammatory signaling pathways, is the root cause of vision loss and the leading cause of blindness. The company’s later-stage clinical development program for ONL1204 currently includes a Phase 2 study in the U.S. for the treatment of macula-off retinal detachment (NCT05730218), a condition for which the compound has been granted orphan drug designation by the United States Food and Drug Administration (FDA). The company is also conducting a Phase 1b clinical trial in patients with geographic atrophy (GA) associated with age-related macular degeneration (AMD) (NCT04744662) and a Phase 1b clinical trial in patients with progressing open-angle glaucoma (NCT05160805) at sites in Australia and New Zealand. Preclinical work is ongoing to enable clinical trials in other disease indications, including inherited retinal degeneration (IRD; also known as retinitis pigmentosa). About ONL TherapeuticsONL Therapeutics (ONL) is a clinical-stage biopharmaceutical company committed to developing first-in-class therapeutics to protect and improve the vision of patients with retinal disease. By advancing a breakthrough technology designed to protect key retinal cells from Fas-mediated cell death, ONL is pioneering a new approach to preserving vision. ONL is developing a platform of products for use in a wide range of blinding diseases, including retinal detachment, glaucoma, AMD and IRD. For more information about ONL Therapeutics, please visit www.onltherapeutics.com.

上海 2024年1月16日 /美通社/ -- 今年1月起，《国家基本医疗保险、工伤保险和生育保险药品目录（2023年）》在全国范围内正式实行。此次目录更新调整了用于治疗多发性骨髓瘤的创新药物伊沙佐米的医保支付范围，为"治疗已接受过至少一种既往治疗的多发性骨髓瘤成人患者"，与说明书适应症一致。这意味着旧版目录中伊沙佐米与来那度胺联用时只支付其中一种的限制已去除，用于多发性骨髓瘤持续治疗的IRd全口服方案（伊沙佐米联合来那度胺、地塞米松）年自付费用大幅降低，患者的用药经济负担将得到极大缓解。 北京积水潭医院血液科主任鲍立教授表示： "伊沙佐米的用药报销限制被取消后，极大地降低了中国多发性骨髓瘤患者的医疗经济负担，将有望进一步发挥IRd方案的应用价值和临床潜力，助力患者坚持持续治疗，提升生活质量。" 多发性骨髓瘤（MM）是第二大常见的血液肿瘤。在我国，患者发病年龄多为60岁以上，发病率也呈上升趋势 [1] 。研究显示，相较于西方国家，中国的MM患者多在确诊时已进展为晚期，高危患者数量更多 [2] 。目前，多发性骨髓瘤依旧是一种不可治愈的疾病，且随着复发次数增多，治疗难度加大，严重加深患者负担，影响生活质量。 近年来，随着临床治疗方案的不断创新突破，多发性骨髓瘤的整体治疗模式向持续治疗模式转化。与传统固定周期治疗相比，持续治疗可以延长疾病控制，改善临床结局，进一步延长患者无进展生存期（PFS）和总生存期（OS） [3],[4] 。但在临床实践中，持续治疗对药物的疗效、不良反应的耐受性、给药便捷程度、患者的依从性等均提出了较高的要求。 多项国内外临床指南提出，治疗方案的选择是实现多发性骨髓瘤持续治疗的关键。伊沙佐米联合来那度胺、地塞米松形成的全口服的IRd治疗方案，是目前唯一 [5] 获批含蛋白酶体抑制剂（PI）的全口服联合方案，在临床实践中可为患者治疗提供更多便利，减少病毒暴露和感染风险，从而提升患者的用药可及性，治疗时间较V-base延长一倍以上 [6] ，助力实现多发性骨髓瘤的长期持续治疗。全球III期临床研究TOURMALINE-MM1 [7] 及中国延展性研究TOURMALINE-MM1 CCS [8] 中，已验证IRd在复发难治性多发性骨髓瘤患者中的有效性和安全性。TOURMALINE-MM1的中国延展研究数据显示 [9] ，相比安慰剂Rd组，IRd组患者的总生存期显著延长达10个月（25.8个月 vs 15.8个月），无进展生存期显著改善67%（6.7个月 vs 4.0个月）。在安全性方面，IRd与安慰剂Rd组比较没有明显增加不良事件。 在旧版医保目录中，伊沙佐米与来那度胺联用时，医保只能支付其中一种。同时，每2个疗程患者需提供治疗有效的证据后方可继续使用医保支付，并且需由三级医院血液专科或血液专科医院医师处方。新版医保目录实行后，这些限制都将被取消，这意味着患者使用IRd方案的年自付费用可降低过半。此外，各地开展的惠民保、补充商业保险等，可在患者医保报销后进行二次报销，也可助力患者进一步减轻经济负担。 审批编号：C-ANPROM/CN/NINL/0824 审批日期： 2024.1 声明： 1.本资料仅为介绍企业业务及经营活动等情况，并不以宣传任何公司产品和/或服务为目的，更不应被理解为就任何药物、医疗器械及治疗方案的选择提供任何意见或建议。 2. 如欲了解任何公司产品、疾病和/或诊疗等相关信息，请务必咨询医疗卫生专业人士。 关于武田制药 武田制药（ 东京证券交易所股票代码：4502 ）（纽约证券交易所股票代码：TAK）是一家总部位于日本、以价值观为基础、以研发为驱动的全球生物制药公司。武田致力于将科学研发成果转化为高度创新药品，为患者的健康生活和美好未来保驾护航。武田专注于四大治疗领域的药物研发：肿瘤、消化、神经科学及罕见病领域，并针对血液制品及疫苗领域进行专项研发投入。我们始终专注于高度创新药物的研发，通过开拓全新治疗方案、增强合作研发引擎实力，打造一条稳健且形式多样的产品管线，助力改善人们的生活。我们的员工遍布于大约80个国家和地区，与当地医疗健康合作伙伴携手，为全球患者带来健康福音。 武田于1994年进入中国，武田中国总部位于上海，在中国大陆的主要业务中心位于北京、上海、天津、广州、香港特别行政区等城市和地区，并在全国各主要城市设有办事处，目前在中国拥有超过2000名员工。随着中国经济的发展和对医疗保健需求的不断增长，中国已经成为武田全球最重要的新兴市场之一。 更多信息，敬请访问 https://www.takeda.com 前瞻性声明 本稿件及与之相关的所分发的任何资料可能含有与武田未来业务、未来状况和运营业绩有关的前瞻性陈述、看法或意见，包括武田的预估、预测、目标和计划。前瞻性陈述常常包含但不限于下列措辞，例如"目标"、"计划"、"认为"、"希望"、"继续"、"预计"、"旨在"、"打算"、"确保"、"将"、"可能"、"应"、"会"、"或许"、"预期"、"估计"、"预测"或类似表述或其否定形式。 本文中的前瞻性陈述仅基于武田截至发布日期的估计和假设。此类前瞻性声明并非是武田或其管理层对未来业绩所做的任何保证，并涉及已知和未知的风险、不确定性和其他因素，包括但不限于：武田全球业务所面临的经济形势，包括日本和美国的宏观经济环境；竞争压力和发展情况；适用法律法规的变动；产品开发项目的成功或失败；监管当局的决策或做出决策的时机；利率和汇率波动；有关已售产品或候选产品安全或功效的索赔或疑问；已收购公司的合并后整合努力的时机和影响；以及能否剥离对武田运营非核心的资产和任何此类剥离的时机，所有这些都可能会导致武田的实际业绩、表现、成就或财务状况与此类前瞻性陈述所描述或暗指的任何未来业绩、表现、成就或财务状况发生重大偏差。 关于以上及可能影响武田结果、业绩、成就或财务状况的其他因素的更多信息，请参阅武田向美国证券交易委员会提交的Form 20-F最新年报"第3项. 关键信息—D. 风险因素"和其他报告，具体请查阅武田网站https://www.takeda.com/investors/reports/sec-filings/或www.sec.gov。武田的未来结果、业绩成就或财务地位可能与前瞻性陈述所言传或意会的内容有实质性差距。收到这一新闻稿的个人不应对任何前瞻性陈述寄予不适切的依赖。武田没有义务更新本新闻稿中的任何前瞻性陈述或公司可能发布的任何其他前瞻性陈述，除非是法律或证券交易规则所要求。历史业绩并不能代表未来业绩，而且本新闻稿中的武田业绩并不能指代，也并非是武田未来业绩的预估、预测或推测。 [1] Liu J, Liu W, Mi L, et al. Incidence and mortality of multiple myeloma in China, 2006–2016: an analysis of the Global Burden of Disease Study 2016. J Hematol Oncol 12, 136 (2019). [2] Liu J, Liu W, Mi L, et al. Incidence and mortality of multiple myeloma in China, 2006–2016: an analysis of the Global Burden of Disease Study 2016. J Hematol Oncol 12, 136 (2019). [3] Palumbo A, Gay F, Cavallo F, et al. Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2015 Oct 20;33(30):3459-3466. [4] Facon T, Dimopoulos MA, Dispenzieri A, et al. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. 2018 Jan 18;131(3):301-310. [5] 截止至2024年1月16日 [6] Robert M. Rifkin. et al. EHA Library. M. Rifkin R. 06/10/22; 357807; P947 [7] Moreau P, Masszi T, Grzasko N, et al. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Apr 28;374(17):1621-34. [8] Hou J, Jin J, Xu Y, et al. Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsedrefractory multiple myeloma China Continuation. J Hematol Oncol. 2017 Jul 6;10(1):137. [9] Hou J, Jin J, Xu Y, et al. Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsedrefractory multiple myeloma China Continuation. J Hematol Oncol. 2017 Jul 6;10(1):137.