This is a non-inferiority patient-centered and pragmatic comparative-effectiveness pregnancy randomized controlled trial (RCT) with postpartum maternal and child follow-up through 2 years of 1,572 individuals with gestational diabetes mellitus (GDM) randomized to oral metformin versus injectable insulin.
This study will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. A total of 1,572 pregnant individuals with GDM who need pharmacotherapy will be recruited at 20 U.S. sites using consistent treatment criteria to metformin versus insulin. Participants and their children will be followed through delivery to two years postpartum.

开始日期2024-08-01

申办/合作机构

The Ohio State University

[+2]

NCT05768191 / Recruiting临床4期IIT

Comparative Efficacy of a Two Daily Mixed Insulin Injection Versus a Basal-bolus Scheme With Human Insulin in a Limited Resources Setting: a Multicenter Randomized Controlled Crossover Clinical Trial

The goal of this clinical trial is to compare glycemic control and variability between children and adolescents with type 1 diabetes treated by a two daily injection of premixed human insulin (Humulin 30/70) and those who have a basal bolus scheme (Humulin N + Humulin R) in a resources limited setting.
The main question it aims to answer is: what is the effectiveness of premixed human insulin on glycemic control? Ten participants will be randomized initially to premix insulin human isophane suspension and insulin human injection (Humulin 30/70) twice daily, and 10 persons to insulin human isophane suspension (Humulin N) twice daily plus regular human insulin (Humulin R) before meals. At the end of the initial 16-wk treatment (period 1), all patients will be crossed over to the alternate treatment arm for an additional 16 wk (period 2). Insulin doses will be adjusted weekly by the clinical site according to a prespecified insulin intensification algorithm to achieve target fasting [<110 mg/dl (6.1 mmol/liter)], bedtime [<130 mg/dl (7.2 mmol/liter)], and premeal [<110 mg/dl (6.1 mmol/liter)] glucose levels until HbA1c was below 7.0%.
Subjects will receive training on the FreeStyle Libre CGMS System, electronic hand-held personal digital assistant (e-diary), and self-monitoring of blood glucose (SMBG), including recording glucose, insulin doses, and symptoms of hypo- or hyperglycemia.

开始日期2023-06-15

申办/合作机构

Université Polytechnique de Bobo-Dioulasso

[+1]

NCT04118920 / Active, not recruiting临床1期IIT

Safety of Topical Insulin Eye Drops for the Treatment of Open-angle Glaucoma

Glaucoma, a leading cause of irreversible blindness worldwide, is characterized by a permanent loss of retinal ganglion cells (RGCs), a group of central nervous system (CNS) neurons that convey visual information from the retina to the brain via their long axons. Clinically, axonal damage in RGC results in a loss of visual field and may lead to blindness. Currently, reducing eye pressure remains the sole target of proven glaucoma therapies. However, many patients continue to lose vision even when standard interventions are implemented, accentuating the unmet need for novel therapies.
Dendrites are processes that determine how neurons receive and integrate information. Dendrite retraction and synapse breakdown are early signs of several neurodegenerative disorders. In mammals, CNS neurons have an extremely limited capacity to regenerate after injury. To date, the ability of mammalian neurons to regrow dendrites and reestablish functional synapses has been largely ignored.
Insufficient insulin signaling has been implicated in diseases characterized by dendritic pathology, notably Alzheimer's disease and glaucoma. A versatile hormone, insulin readily crosses the blood-brain-barrier and influences numerous brain processes. In a mouse model of optic nerve transection, our team showed that insulin administration after optic nerve injury promoted robust dendritic regrowth, RGCs survival and retinal responses rescue, providing the first evidence of successful dendrite regeneration in mammalian neurons. Our research validates insulin as a powerful medication to restore dendritic function in glaucoma, forming the basis for using insulin as glaucoma treatment in humans.
Currently, insulin is approved for diabetes. Adverse events of systemic insulin include hypoglycemia, hypokalemia, lipodystrophy, allergies, weight gain, peripheral edema and drug interactions. Experimental use of ocular topical insulin have been tested in small cohorts of healthy individuals and diabetic patients, reporting no significant adverse events. However, these protocols varied in insulin posology and adverse events were only touched upon briefly, indicating the necessity to better characterize the safety profile of such off-label use of insulin before its application as a neuroprotective and regenerative treatment for glaucoma.
In this study, the investigators hypothesize that topical ocular insulin (up to 500 U/ml) at once per day dosing is safe in patients with open angle glaucoma.

开始日期2023-03-27

申办/合作机构

Fondation du Centre Hospitalier de l'Université de Montréal

100 项与人胰岛素(Eli Lilly & Co.) 相关的临床结果

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100 项与人胰岛素(Eli Lilly & Co.) 相关的转化医学

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100 项与人胰岛素(Eli Lilly & Co.) 相关的专利（医药）

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187

项与人胰岛素(Eli Lilly & Co.) 相关的文献（医药）

2024-12-01·American journal of ophthalmology case reports

Topical insulin to treat a conjunctival defect after glaucoma surgery: A case report

Article

作者: Docherty, Gavin ; Burgos-Blasco, Barbara ; Yeung, Sonia N. ; Iovieno, Alfonso

Purpose:

Insulin has been postulated as a novel and effective treatment for re-epithelialization of the ocular surface and different pathologies have been suggested as possible indications.

Observations:

A 69-year-old diabetic male was referred for a left non-healing conjunctival epithelial defect over the superotemporal scleral patch used in the placement of the Ahmed ClearPath. In the left eye, he was on latanoprost/timolol once daily, prednisolone 1 % once daily and tobramycin/dexamethasone ointment at night. Best-corrected visual acuity was 20/20 in the right eye and 20/25 in the left eye. Slit lamp examination of the left eye showed patches of avascular scleral tissue nasally and superiorly, conjunctival and Tenon defect over a thin avascular scleral patch graft. The patient was started on Humulin insulin 1UI/mL 6 times a day and the defect healed after 3 months of treatment.

Conclusions and importance:

Insulin eye drops may be used in the treatment of chronic conjunctival epithelial defects following implantation of glaucoma drainage devices.

2024-08-09·ACS Pharmacology & Translational Science

Therapeutic Insulin Analogue Concentrations at Infusion Sites Enhanced the Pro-Inflammatory Response and Apoptosis in an In Vitro Macrophage-Material Interaction Model

Article

作者: Woodhouse, Kimberly A ; Kuo, Luke ; Fitzpatrick, Lindsay E ; Zhang, Yuxi

Continuous subcutaneous insulin infusion for Type 1 diabetes relies upon insulin infusion sets (IIS) to reliably deliver insulin to a subcutaneous depot, where it is absorbed into systemic circulation. However, IIS are plagued by short wear times and high failure rates, due in part to inconsistent insulin absorption that can arise over time. While emerging evidence suggests that the local inflammatory response to the IIS cannula may impact both wear times and unreliable insulin adsorption, the mechanisms are poorly understood. Here, we investigated the effects of local infused insulin concentrations on the biomaterial host response to better understand the underlying factors that limit the IIS performance. We first modeled the insulin concentration for a constant basal infusion rate to select a relevant insulin concentration range of 0.1-10 U/mL within the infusion site. We then examined the influence of a commercial insulin analogue (Humulin-N) using an in vitro macrophage-material model, which uses adsorbed fibroblast lysate (containing damage-associated molecular patterns) to activate macrophages and recapitulates macrophage responses on implanted biomaterials. RAW-Blue macrophages cultured on lysate-adsorbed surfaces had increased nuclear factor-κB (NF-κB) and activating protein 1 (AP-1) activity and intracellular reactive oxygen species (ROS) accumulation compared to control surfaces. Humulin-N concentration (0.5-10 U/mL) enhanced the NF-κB/AP-1 activity and ROS accumulation in macrophages on lysate-adsorbed surfaces. However, Humulin-N had no effect on NF-κB/AP-1 or ROS in the absence of the inflammatory stimulus. Additionally, high insulin concentrations arising from therapeutic doses induced macrophage apoptosis with and without adsorbed lysate. This study contributes to emerging evidence that infused insulin affects the tissue response to IIS.

2024-06-01·British journal of pharmacology

Are insulin sensitizers the new strategy to treat Type 1 diabetes? A long‐acting dual amylin and calcitonin receptor agonist improves insulin‐mediated glycaemic control and controls body weight

Article

作者: Karsdal, Morten Asser ; Larsen, Anna Thorsø ; Melander, Simone Anna ; Henriksen, Kim

Abstract:

Background and Purpose:

Insulin therapies for Type 1 diabetes (T1D) have limitations, such as glucose fluctuations, hypoglycaemia, and weight gain. Only pramlintide is approved with insulin. However, its short half‐life limits efficacy, requiring multiple daily injections and increasing hypoglycaemia risk. New strategies are needed to improve glycaemic control. Dual amylin and calcitonin receptor agonists are potent insulin sensitizers developed for Type 2 diabetes (T2D) as they improve glucose control, reduce body weight, and attenuate hyperglucagonemia. However, it is uncertain if they could be used to treat T1D.

Experimental Approach:

Sprague Dawley rats received a single intravenous injection of streptozotocin (STZ) (50 mg·kg−1) to induce T1D. Humulin (1 U/200 g·day−1 or 2 U/200 g·day−1) was continuously infused, while half of the rats received additional KBP‐336 (4.5 nmol·kg−1 Q3D) treatment. Bodyweight, food intake, and blood glucose were monitored throughout the study. An oral glucose tolerance test was performed during the study.

Key Results:

Treatment with Humulin or Humulin + KBP‐336 improved the health of STZ rats. Humulin increased body weight in STZ rats, but KBP‐336 attenuated these increases and maintained a significant weight loss. The combination exhibited greater blood glucose reductions than Humulin‐treated rats alone, reflected by improved HbA1c levels and glucose control. The combination prevented hyperglucagonemia, reduced amylin levels, and increased pancreatic insulin content, indicating improved insulin sensitivity and beta‐cell preservation.

Conclusion and Implications:

The insulin sensitizer KBP‐336 lowered glucagon secretion while attenuating insulin‐induced weight gain. Additionally, KBP‐336 may prevent hypoglycaemia and improve insulin resistance, which could be a significant advantage for individuals with T1D seeking therapeutic benefits.

项与人胰岛素(Eli Lilly & Co.) 相关的新闻（医药）

2024-09-03

·BioSpace

Opinion: The FDA Needs a Dedicated ‘Center for Rare Diseases’

Taylor Tieden for BioSpace The agency’s inertia and bureaucratic roadblocks are throttling hope for millions of patients. A new center of excellence would provide a solution. When I joined the FDA to be its “biotechnology czar” more than 40 years ago, genetic engineering was still a new concept. To fully grasp the nuances of the latest technological advances, we brought together experts in different scientific disciplines from across the organization. The first “biopharmaceutical” was human insulin synthesized in genetically engineered E. coli bacteria. Despite the novelty, we decided that because the FDA had prodigious experience with insulins sourced from pig and cow pancreases and also with drugs derived from various microorganisms, recombinant DNA techniques would be viewed as an extension or refinement of long-used and familiar methods for making drugs. Thus, no sui generis policies were required. That proved to be a historic, precedent-setting–and correct—decision. The human insulin, Humulin, was approved in a record-setting five months at a time when the average approval time for a New Drug Application was 31.5 months. Biopharmaceuticals now dominate the list of highest-revenue drugs and are critical to the health of tens of millions of patients. However, when it comes to another high-impact category of drugs, those for rare diseases, the FDA has a long way to go. When it comes to approving treatments for rare diseases, the Agency’s inefficient structure creates a confusing patchwork of policies that can lead to an inconsistent review process. There are over 10,000 rare diseases, some affecting only hundreds or even just dozens of Americans. In total, more than 30 million Americans live with a rare disease, but this large, vulnerable cohort has very little visibility outside of patients’ communities and support networks. There is currently no FDA-approved treatment for an estimated 95% of rare diseases, so millions of Americans (many of whom are children) face premature mortality, disability, severe pain, repeated hospitalizations and a drastically diminished quality of life. With such a large segment of our population living in a world without cures or treatments, you would think the FDA and its parent, the Department of Health and Human Services (HHS), would be doing everything in their power to usher in a new wave of innovation. But, perhaps unsurprisingly in government bureaucracies, they lack focus, coordination and an overarching strategy for addressing rare diseases. To become more effective in this area and to give hope to patients living on borrowed time, the FDA should establish a cross-cutting entity with a single leader to focus resources on the goal of getting treatments to rare-disease patients who need them without unnecessary delays. The FDA is Throttling Innovation In 1983 the Orphan Drug Act, which incentivized researchers to invest in new drugs and devices for rare diseases, was enacted. Before that landmark law was passed, just 38 rare disease drugs had been approved by the FDA; today, that number is well over 1,000. This is good news for patients, but much more must be done. The FDA continues to add and move boxes around on its organizational chart, but rare diseases continue to get short shrift, and innovation has suffered. Rare diseases are lumped into the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, which dilutes both the expertise and focus on rare diseases. A further complication is that many therapies for rare diseases are classified as “biologics,” which are regulated not by the Center for Drug Evaluation and Research but by the Center for Biologics Evaluation and Research. Different groups of bureaucrats may have different biases and approaches, which causes the goalposts for approval to be constantly shifted, leading to additional, costly, difficult-to-perform new trials. This situation arises because expertise in the highly specialized fields required to understand the spectrum of rare diseases and the mechanisms for treating them is scattered across the Agency. The conflicting guidance and advice given by different components of the FDA is not a prescription for efficiency and expert oversight, let alone advocacy for rare disease drugs. And the involvement of regulators who advocate for the expeditious testing and approval of the drugs is important: There is a saying in government that “Personnel = Policy.” Unfortunately, many pharmaceutical companies decide it’s simply not worth the hassle of the additional regulatory burden, or that they can’t afford the cost of providing drugs on a “compassionate use” basis and gathering new data. Consider these recent examples: In April, after years of deliberations, the FDA finally agreed to consider a drug to help an estimated patient population of 130–150 Americans. The review had been delayed after the agency gave the drugmaker conflicting requirements for data it needed to submit, and prior to the FDA’s acceptance of its application, the company had planned to abandon the drug. The same month, a company founded a quarter-century ago went bankrupt after the FDA kept moving the goalposts on its treatment for a disease that affects one in four million newborns and has been shown to extend children’s lives. (Inexplicably, the agency also failed to grant the company an approval or even an Emergency Use Authorization for its drug to treat COVID .) A Call to Action To prevent unnecessary roadblocks to vital medicines, the FDA needs an organization that understands and will focus on advocacy for rare-disease drugs. Last year, the FDA made a step in the right direction when it launched the Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program to accelerate “the pace of development of certain CBER- and CDER-regulated products (novel drug and biological products) that are intended to treat a rare disease.” To achieve this, the agency said: Selected [drug developers] will be able to interact with FDA through rapid, ad-hoc communication mechanisms to provide a mechanism for addressing program-specific development issues, including but not limited to clinical study design, choice of control group, fine-tuning the choice of patient population, leveraging nonclinical information, or product characterization. The FDA’s recent establishment of a Rare Disease Innovation Hub is another noteworthy advance in addressing the needs of patients with rare diseases, but more is needed. Building on these efforts, the FDA should now create a new organization resembling the agency’s Center of Excellence for Oncology to focus on getting more treatments to patients who have precious little time or options. Developing a Center of Excellence (or “Intercenter Institute”) for Rare Diseases under a single, dedicated director would further streamline rare disease development. This idea, which has the support of bipartisan members of Congress , would aggregate specialists and researchers on different types of rare diseases and organ systems to expedite the testing, evaluation and approval of drugs for rare diseases. Ultimately, it would enhance cross-Agency collaboration and expedite drug delivery to patients who currently lack options for treatment. Many of these treatments will be cutting-edge gene and cell therapies and combination therapies that require expertise across multiple disciplines to fully understand how they work. Institutional change won’t be easy, but it is necessary. A Center for Excellence for Rare Diseases would be an excellent start.

上市批准孤儿药

2024-06-27

·同写意

诺和诺德是如何赚到第一桶金的？

同写意20周年大会：中国医药创新未来之路！“意”同创新，穿越周期，赢取未来。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！ 1922年，4名来自多伦多的研究员成功从动物胰脏中提取了胰岛素，自此人类找到了针对糖尿病的治疗方案。尽管当时的胰岛素已经能够有效降低人类血糖，但由于该种胰岛素是经由动物碾碎了的胰脏中提取的，产品纯度并不高，极容易引发全身瘙痒、皮疹等副作用，严重者甚至会出现过敏性休克。为了降低动物胰岛素产品的副作用，以礼来为首的胰岛素厂商开启长达60年的“提纯”竞赛。在这场竞赛中，礼来、安万特、诺和等头部公司不断投资，最终成功将胰岛素中的污染物量由最初的50000ppm（ppm，即每百万容量中含有污染物的量）降低至1980年的10ppm。这场胰岛素“提纯”竞赛最终在1982年被画上句号。“基因工程技术先驱”基因泰克公司成功通过大肠杆菌制造重组人胰岛素，并在随后将这项技术授权给了礼来。自此，礼来终于将胰岛素浓度提升至了100%，一切都预示着它即将从这场胰岛素“百年之战”中胜出。但故事的走向并没有如礼来所料的那样发展，反而在这一过程中诞生了它的“一生之敌”诺和诺德。 1 礼来：困于“延续性思维” 大多数技术变革都是沿着一个既定轨道发展的，如在早期的胰岛素赛道，纯度的不断提升就是技术变革的核心路径。对于礼来等头部玩家来说，只要能够不断生产出纯度更高的胰岛素产品，就能更显著地降低副作用率，从而获得更高的产品溢价。正是通过一次又一次的技术迭代，礼来逐渐积累起了竞争优势，因此它才会如此痴迷于“提纯”胰岛素。也就是说，胰岛素赛道早期竞争，是沿着纯度提升这条线延续性发展的。基因泰克克隆的人胰岛素很好地解决了动物胰岛素产生免疫反映的问题，几乎没有了副作用。对于当时的糖尿病患者来说，这是一款完美的产品，但这款完美的产品却并没有给礼来带来充足的回报。为了产业化量产人胰岛素优泌林，礼来在上世纪80年代就投入了近10亿美元资金，寄希望于这款跨时代的产品垄断整个胰岛素市场。因此，礼来给优泌林的定价并不高，仅比常规动物胰岛素提价25%。然而，这款跨时代产品的销售数据却并不佳，礼来甚至发现优泌林很难卖出比动物胰岛素更高的溢价。尽管最终人胰岛素还是全面取代了动物胰岛素，但对比礼来初期的极高投入，这一次“跨时代创新”显然并没有给礼来带来商业化的胜利。剖析优泌林难以形成溢价的原因，正在于“延续性思维”的固化。在产业发展初期，由于动物胰岛素极高的污染物比例，因此纯度是糖尿病人最关心的事情。厂商只要延续这一技术变革路线，就能很轻松地获得商业层面的成功。但“提纯”胰岛素毕竟有一个上限，随着技术的不断精进，业界距离这个上限也就越来越近。至1980年胰岛素纯度已经提升至10ppm，这个纯度几乎已经达到了100%。这时候礼来痴迷于完美的胰岛素产品并没有错，但纯度却早已并不是胰岛素竞争的核心主线了。尽管动物胰岛素仍会导致部分糖尿病患者产生免疫反应，可相对于最初的副作用率已经有了显著降低，动物胰岛素已经可以满足大多数糖尿病患者的需求。在这一基础上，只有产生免疫反应的少部分患者才会去选择价格更高的人胰岛素，而在大多数患者眼中它更像是一种“智商税”。沉迷于“延续性思维”，忽略了胰岛素发展的主要矛盾，这就是为何礼来优泌林当时没有取得预期中成功的原因。产业发展的“第一性”不是一成不变的，而是随着技术变革而不断生变的。 2 诺和诺德：填补临床空白的弯道超车既然礼来错估了胰岛素80年代发展的“第一性”，那么当时糖尿病患者核心痛点到底是什么呢？正是临床未满足需求依从性。当时胰岛素虽然已经能够满足大多数糖尿病患者的降糖需求，但每天注射胰岛素依然是一件较为繁杂的事情。糖尿病患者只能将一次性的在注射器中装满一天的胰岛素，每次注射都需要挤出气泡，并且还要控制好单次注射量。这就使得一次简单的胰岛素注射往往需要花费数分钟时间。今天的人们或许很难感知到当时糖尿病患者的痛苦，这不仅是一种肉体上的痛苦，更是每天小心谨慎注射胰岛素带来的心灵煎熬。这个细微的临床需求切片被丹麦的诺和公司准确洞察，因此在礼来全面推广人胰岛素时，诺和公司（诺和诺德前身）却在尝试通过设计一种更为便捷的注射器来争夺市场。在礼来人胰岛素销售不及预期的1986年，诺和公司成功研发出了新一代胰岛素注射笔——诺和针。诺和针相当于一只特殊设计的钢笔，内含好几周用量的胰岛素，糖尿病人在注射胰岛素时，只需按下注射键，就能在10秒钟内完成胰岛素注射。图：1985年诞生的诺和针，来源：官网与礼来公司苦苦支撑优泌林25%的溢价率不同，诺和公司的诺和针轻松就实现了单位胰岛素30%的销售溢价，直接使得诺和公司胰岛素市场占比大幅提升。借助于诺和针的成功，诺和公司在两年后成功收购了同样来自于丹麦的诺德公司，并在1989年推出了世界上第一个预充型胰岛素注射器NovoLet。依靠诺和针的高度便捷性，合并后的诺和诺德占据了全球54.4%的市场份额，反超礼来成为全球第一。诺和针，正是诺和诺德挖到的第一桶金，这也奠定了诺和诺德后续贴近临床需求的发展策略。 3 小公司如何击败巨无霸？与成功抢下基因泰克人胰岛素的礼来相比，诺和公司只能算得上是一家小公司。但也正是这家小公司，成功抓住了礼来战略失误的契机，最终实现市场占有率的逆袭。无论是品牌层面、技术层面，还是资本层面，礼来都是当时胰岛素赛道的绝对一哥，这样一家大企业究竟为何会失败呢？这实则是一种必然。在产业发展初期，由于没有产品能够满足用户需求对于功能的需求，因此产业竞争的标准就是功能性，也就是胰岛素的纯度。可是当胰岛素纯度提升到一定程度后，市场中大多数的主流胰岛素已经都能够满足用户的需求，因此头部公司的竞争优势就会下降。当产品性能已经足够时，性能的提升就不会带来如之前一样的竞争力，用户关注的焦点也逐渐从功能性转变为便捷性、性价比等其他因素。然而，由于一直以来的行业领先优势，致使龙头公司陷入技术为王的误区，最终导致他们将更多的资金与精力全部投入到更高性能的技术路线上。或许这样的努力在某些时候可以取得成效，但行业终会变化，大公司迟早会因错押技术路线而吃大亏。而那些产业中处于追赶地位的玩家，往往更容易感知到这种变化，所以世界商业史中才总会出现以弱胜强的经典案例。礼来，并不是第一个被逆袭的大公司，也绝不会是最后一个。大公司天生缺少对于技术变革路线迁移的敏感度，而更愿意沿用之前的成功思路，这正是所谓的路径依赖。三十年后，胰岛素已经不再是医药产业竞争的核心战场，但专注于临床未满足需求的诺和诺德依然能够在降糖药物GLP-1中找到减肥的新需求。在GLP-1减肥适应症上，诺和诺德同样展现的是实用主义，在长效GLP-1司美格鲁肽符合用户需求后，开始转而重点研发口服药物，以此提升依从性；而礼来似乎依然秉持着当年完美主义的风格，追求更高的减肥数据，固然换来现阶段全球最高的市值，但依然存在客观风险。只有创新才能带来新机遇，不断填补临床空白的医药产业更是如此。从临床未满足需求出发，企业才能真正捕捉到产业发展过程中的机会，只不过太多的大公司并不愿意去聆听外界声音，而是沉溺于属于自己构建的宏伟叙事之中。万物皆有周期，盛极必衰乃盈虚一定之理。大公司想要维系自身的优势，必须放弃自身大公司定位，而是以产业探索者身份去持续耕耘。医药公司，填补临床空白需求一定是最重要的，无论途径是通过疗效提升、技术迭代，还是依从性提升。近期直播推荐:

医药出海

2024-05-20

·GlobeNewswire-Health Care

At278 Ultra-Concentrated Ultra-Rapid Acting Insulin Demonstrates Superiority in Phase i Clinical Trial in Overweight and Obese People With Type 2 Diabetes

Arecor Therapeutics plc(“Arecor” or “the Company”) AT278 ULTRA-CONCENTRATED ULTRA-RAPID ACTING INSULIN DEMONSTRATES SUPERIORITY IN PHASE I CLINICAL TRIAL IN OVERWEIGHT AND OBESE PEOPLE WITH TYPE 2 DIABETES AT278 demonstrates significantly accelerated PK/PD profile compared to NovoRapid® and Humulin® R U-500 in people with Type 2 Diabetes and high BMIConfirms previous trial results in people with Type 1 diabetes, demonstrating AT278 can maintain fast and superior onset of action and glucose lowering profile irrespective of diabetes type and BMIEnables delivery of a highly concentrated, low volume injection, offering more effective mealtime glucose control to meet growing unmet need in patients requiring high daily doses of insulin Creates potential to be the first, and only, ultra-concentrated (500 U/mL) ultra-rapid insulin product enabling miniaturisation of next-generation insulin pumpsCompany will host a CEO and key opinion leader webinar to discuss the results on Tuesday 21 May at 14.30 BST Cambridge, UK, 20 May 2024. Arecor Therapeutics plc (AIM: AREC), the biopharmaceutical group advancing today’s therapies to enable healthier lives, today announces that its ultra-concentrated, ultra-rapid acting insulin candidate, AT278, met all primary and secondary endpoints, and also demonstrated superiority to NovoRapid® and Humulin® R U-500, in a Phase I clinical trial in Type 2 diabetics with a high body mass index (BMI). AT278 (500 U/mL) is an ultra-concentrated, ultra-rapid acting, novel formulation of insulin that accelerates the absorption of insulin post injection, even when delivered at a high concentration, and hence a lower injection volume. With no concentrated (>200 U/mL), rapid acting insulins on the market, AT278 has potential to be the first, and only, insulin available to the growing number of patients with high daily insulin requirements. Sarah Howell, Chief Executive Officer of Arecor, said: "We are delighted with the clinical results from this second Phase I study, demonstrating AT278’s superiority over NovoRapid® and Humulin® R U-500 in Type 2 diabetics with a high BMI. They further add to the positive results from our previous clinical study in Type 1 diabetic patients, where superiority was also demonstrated. This is a significant step in AT278’s development and extends our confidence in its clear potential to provide a superior insulin treatment option that lowers burden and improves outcomes for people living with diabetes who require high daily doses of insulin. Such patients make up a large segment of the target market. In addition, as the only concentrated, yet very rapid acting, insulin in development, AT278 has the capability to disrupt the market by enabling the next generation of truly miniaturised, longer-wear insulin pumps, a key focus for patients, physicians and the industry.” Many Type 2 diabetics with a high BMI are currently not well controlled, and improved treatments options such as AT278 are needed to reduce patient burden through fewer injections per day, reduced injection volumes and dosing flexibility around mealtimes. This lowering of burden for patients improves treatment adherence and, allied with AT278’s superior efficacy, should improve both blood glucose control and outcomes. In addition, a truly ultra-rapid, ultra-concentrated insulin is a critical step towards next-generation miniaturised and long-wearing insulin pumps, which are predicted to transform future diabetes management. Professor Thomas Pieber, Principal Investigator for the ARE-278-104 clinical trial, said: “These results are highly significant, AT278 has clearly demonstrated faster insulin absorption with an accelerated Pharmacokinetic (PK) and Pharmacodynamic (PD) profile compared to the lower concentration standard insulin aspart (NovoRapid®). The PK/PD profile of AT278 (500 U/mL) was also greatly accelerated compared to Humulin® R U-500 (500 U/mL). Together with its superior profile in the earlier Phase I clinical study in Type 1 diabetic patients1 AT278 has demonstrated its ability to maintain a fast and superior onset of action and glucose lowering profile irrespective of diabetes type and BMI. This makes AT278 completely unique in the competitive field of insulin analogues. Not only does it have the potential to significantly improve post-prandial glucose control whilst lowering burden for anybody with diabetes who has a high daily insulin need, it can act as a catalyst in the development of miniaturised insulin delivery systems, where the size of existing devices is a significant barrier to use for many patients.” In the double-blind, randomised, two-way crossover study, the pharmacokinetic (PK)/pharmacodynamic (PD) and safety profiles of a single subcutaneous (SC) dose of 0.5 U/kg AT278 (500 U/mL) were compared with those of a single SC dose of 0.5 U/kg NovoRapid® (100 U/mL), a currently available gold standard, rapid acting insulin treatment, in 39 participants with Type 2 diabetes within a BMI range of 25 and 39 kg/m2, in a euglycemic clamp setting. The PK/PD profile of 0.5 U/kg AT278 (500 U/mL) was also compared to a single SC dose of 0.5U/kg Humulin® R U-500 (500 U/mL) in an open label manner. The trial met the primary endpoint of non-inferiority with respect to glucose lowering actions compared with NovoRapid®AT278 (500 U/mL) demonstrated a significantly accelerated (superior) early PK/PD profile compared to NovoRapid® (100 U/mL), despite a 5-fold increase in concentrationAT278 (500 U/mL) demonstrated a significantly accelerated (superior) PK/PD profile compared to Humulin® R U-500 (500 U/mL), the only other insulin available at a concentration of 500 U/mL No safety signals were detected With around 537m people living with diabetes worldwide, there are growing numbers of people who require insulin to manage their blood glucose and, for many, their diabetes is still poorly controlled. There is a growing need for highly concentrated, much faster, and more physiological insulins to effectively manage diabetes. In the US alone, nearly 10% of insulin scripts written in 2022 were for products with a concentration of >100 U/mL2. Furthermore, despite the improvements in outcomes among people with diabetes who use insulin pumps and automated delivery systems, they are still only used by less than 40% of people with Type 1 diabetes and less than 10% of people with Type 2 diabetes in the US3. The size and short duration of wear of existing insulin pumps remains a significant barrier to use. AT278 has the potential to be the only highly concentrated, ultra-rapid acting insulin to enable the next generation of miniaturised, longer wear insulin pumps. The insulin pump market is valued at circa $5.5bn market today4, with a significant opportunity for substantial growth in this market by expanding use across the Type 1 and Type 2 patient population that can be further enabled by AT278 and a next generation insulin pump. A full analysis of the trial data is now underway to enable the Company to determine and pursue a strategy for AT278 that maximises value for shareholders and patients. Detailed data from the trial will be submitted for publication and presentation at a future international diabetes conference. AT278 clinical results CEO and KOL webinar - Tuesday 21 MayDr Sarah Howell, Chief Executive Officer, and Professor Thomas Pieber, Principal Investigator for the ARE-278-104 clinical trial and Professor of Medicine, Head of the Division of Endocrinology and Metabolism and Chairman of the Department of Internal Medicine at Medical University of Graz, Austria will host a CEO and key opinion leader webinar to discuss the clinical results on Tuesday 21 May at 14.30 BST. To register to join the live webcast click here and to register for the conference line to ask questions click here. Please contact ICR Consilium for details on arecor@consilium-comms.com. This announcement contains inside information for the purposes of the retained UK version of the EU Market Abuse Regulation (EU) 596/2014 ("UK MAR"). -ENDS- References Pharmacokinetics and Pharmacodynamics of a Novel U500 Insulin Aspart Formulation: A Randomized, Double-Blind, Crossover Study in People With Type 1 Diabetes Care 2023;46(4):757–764: https://doi.org/10.2337/dc22-10542022 reports from Symphony. Retrieved October 2023Seagrove Partners Diabetes Bluebook 2022Insulin pump company annual reports and Company estimates For more information, please contact: Arecor Therapeutics plcwww.arecor.comDr Sarah Howell, Chief Executive OfficerTel: +44 (0) 1223 426060Email: info@arecor.com Susan Lowther, Chief Financial OfficerTel: +44 (0) 1223 426060Email: info@arecor.com Panmure Gordon (UK) Limited (NOMAD and Broker) Freddy Crossley, Emma Earl (Corporate Finance)Rupert Dearden (Corporate Broking)Tel: +44 (0) 20 7886 2500 WG Partners LLP (Financial Advisor) Nigel Barnes, Satheesh NadarajahDavid Wilson, Claes SpangTel: +44 (0)203 705 9321 ICR Consilium Chris Gardner, David Daley, Lindsey NevilleTel: +44 (0) 20 3709 5700Email: arecor@consilium-comms.com Notes to Editors About Arecor Arecor Therapeutics plc is a globally focused biopharmaceutical company transforming patient care by bringing innovative medicines to market through the enhancement of existing therapeutic products. By applying our innovative proprietary technology platform, Arestat™, we are developing an internal portfolio of proprietary products in diabetes and other indications, as well as working with leading pharmaceutical and biotechnology companies to deliver therapeutic products. The Arestat™ platform is supported by an extensive patent portfolio. For further details please see our website, www.arecor.com

临床1期临床结果

100 项与人胰岛素(Eli Lilly & Co.) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03230	人胰岛素(Eli Lilly & Co.)	A10AF01 A10AD01 A10AC01	DB00030

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
糖尿病	美国	Eli Lilly & Co.	1985-09-30
1型糖尿病	美国	Eli Lilly & Co.	1982-10-28
2型糖尿病	美国	Eli Lilly & Co.	1982-10-28

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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


NCT02588950 (CTgov)	临床1期	2型糖尿病	11	U-500 insulin (U-500R) (100-U Bolus U-500R SC)	鑰膚糧襯鬱壓獵膚網膚(淵積遞膚獵繭選鹹構膚) = 鏇網網艱艱醖願選艱積衊鑰窪衊夢衊壓構獵鬱 (鹹餘鏇淵築憲願衊憲憲, 衊廠膚窪鏇餘遞築網範 ~ 網夢窪憲鹹鏇夢憲壓醖) 更多	-	2023-10-18
				U-500R+insulin (100-U Bolus U-500R CSII)	鑰膚糧襯鬱壓獵膚網膚(淵積遞膚獵繭選鹹構膚) = 憲淵鑰憲艱廠襯構獵遞衊鑰窪衊夢衊壓構獵鬱 (鹹餘鏇淵築憲願衊憲憲, 糧築獵鹽遞窪簾窪顧壓 ~ 範淵衊蓋觸選蓋鬱醖遞) 更多
NCT03511521 (CTgov)	临床4期	胰岛素抵抗 \| 类固醇诱导的高血糖	3	Glargine+Humulin N+Novolin N+insulin aspart (NPH Insulin)	鏇憲鬱願鹹艱獵願憲製(積淵網衊齋鏇艱艱糧獵) = 築簾選遞廠築鹹糧衊遞膚衊獵範範齋廠選鏇築 (醖壓鬱廠構簾遞鹹糧醖, 鬱獵夢鹹壓選鏇憲選願 ~ 艱蓋範網衊網鹽襯網製) 更多	-	2020-09-11
				Glargine+insulin aspart (Basal/Bolus Insulin)	鏇憲鬱願鹹艱獵願憲製(積淵網衊齋鏇艱艱糧獵) = 艱網艱艱蓋衊繭築襯獵膚衊獵範範齋廠選鏇築 (醖壓鬱廠構簾遞鹹糧醖, 築觸鹹齋糧廠繭憲願鹽 ~ 選觸構襯蓋夢糧鹽鹽壓) 更多
ADA2020	N/A	2型糖尿病	-	U-500 regular insulin	鏇製遞鹹鑰餘廠餘糧築(艱築窪憲鏇窪鬱鹽艱糧) = 夢淵壓醖憲積憲糧齋壓衊夢蓋膚積餘襯製憲鬱 (簾獵繭醖鹽鏇觸鹹網構 ) 更多	-	2020-06-01
NCT02561078 (VIVID, CTgov)	临床3期	2型糖尿病	420	Human regular U-500 insulin (CSII) (Human Regular U-500 Insulin Administered by CSII)	蓋簾鬱積廠窪築範獵遞(艱餘鏇淵範淵餘觸簾選) = 觸憲齋獵齋壓遞積蓋積鹽艱廠構鬱選顧齋鏇艱 (鏇範襯鏇製遞蓋願齋衊, 糧鹽顧鏇夢鹹選鑰壓廠 ~ 廠淵蓋遞壓夢鹹積遞膚) 更多	-	2020-05-20
				Human regular U-500 insulin (MDI) (Human Regular U-500 Insulin Administered by MDI)	蓋簾鬱積廠窪築範獵遞(艱餘鏇淵範淵餘觸簾選) = 憲鹹網艱蓋鏇齋襯鑰淵鹽艱廠構鬱選顧齋鏇艱 (鏇範襯鏇製遞蓋願齋衊, 鏇獵鹹餘製襯範築鬱鏇 ~ 積齋膚積廠築範淵選鏇) 更多
NCT01774968 (Pubmed \| Endocr Pract)	临床4期	2型糖尿病	325	Thrice-daily U-500R	壓衊醖網鏇艱構憲選鏇(鹹憲獵築製簾鬱觸蓋糧) = 鹹餘獵醖夢製艱鬱襯鏇範範艱製獵繭構廠齋齋 (淵選鏇夢鹽憲餘淵膚鑰 ) 更多	-	2015-07-01
				Twice-daily U-500R	壓衊醖網鏇艱構憲選鏇(鹹憲獵築製簾鬱觸蓋糧) = 衊蓋獵憲夢鬱簾鹽壓遞範範艱製獵繭構廠齋齋 (淵選鏇夢鹽憲餘淵膚鑰 ) 更多
NCT01774968 (CTgov)	临床4期	2型糖尿病	325	Human Regular U-500 Insulin (Human Regular U-500 Insulin TID)	夢鑰淵艱繭遞獵願願願(醖夢衊簾繭淵獵醖繭築) = 壓窪顧願鹽繭淵艱窪鹹齋醖簾獵鑰夢願觸淵鑰 (壓醖襯窪鬱廠餘顧淵餘, 蓋餘窪觸鏇鏇鹹齋構膚 ~ 鹹選鑰衊築網築襯鏇餘) 更多	-	2015-05-12
				Human Regular U-500 Insulin (Human Regular U-500 Insulin BID)	夢鑰淵艱繭遞獵願願願(醖夢衊簾繭淵獵醖繭築) = 鬱願鏇觸廠餘積網範壓齋醖簾獵鑰夢願觸淵鑰 (壓醖襯窪鬱廠餘顧淵餘, 鬱廠鏇鹽鏇襯遞膚簾鹽 ~ 觸齋淵醖糧齋憲繭鏇膚) 更多