Grupo Fernandes Vieira

Airsupra is the first and only rescue medication approved in the US for as-needed use to reduce risk of asthma exacerbations Approval based on successful Phase III trial programme conducted by Avillion in more than 4,000 patients under an exclusive clinical co-development agreement with AstraZeneca Continues Avillion's 100% success rate in clinical co-development partnerships across multiple therapeutic areas LONDON, Jan. 11, 2023 /PRNewswire/ -- Avillion LLP, a drug development company focused on the co-development and financing of pharmaceutical candidates from proof-of-concept through to regulatory approval, announces that the US Food and Drug Administration (FDA) has approved AstraZeneca's Airsupra (albuterol/budesonide, formerly known as PT027) for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in people with asthma aged 18 years and older. Airsupra is a first-in-class, pressurised metered-dose inhaler (pMDI), fixed-dose combination rescue medication containing albuterol, a short-acting beta2-agonist (SABA), and budesonide, an anti-inflammatory inhaled corticosteroid (ICS). The US approval was based on positive results from a global Phase III clinical trial programme for Airsupra comprising four studies involving more than 4,000 patients (including the MANDALA and DENALI trials1,2), which was conducted successfully by Avillion under an exclusive clinical co-development agreement with AstraZeneca. Under its 2018 agreement, Avillion had regulatory responsibility including filing the New Drug Application (NDA) through to FDA approval in the US. Following this approval, AstraZeneca has the option, upon making certain financial payments to Avillion, to commercialise Airsupra in the US. This milestone continues Avillion's 100% successful rate in clinical co-development partnerships for the global pharmaceutical and biotech industry. In MANDALA, Airsupra significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate to severe asthma when used as an as-needed rescue medication in response to symptoms.1 The results from the MANDALA trial were published in the New England Journal of Medicine in May 2022.1 In DENALI, Airsupra significantly improved lung function compared to the individual components, albuterol and budesonide, in patients with mild to moderate asthma.2 The safety and tolerability of Airsupra in both trials were consistent with the known profiles of the components,1,2 with the most common adverse events including headache, oral candidiasis, cough and dysphonia.3 The co-development partnership between AstraZeneca and Avillion has recently expanded to include the BATURA study, a randomised Phase IIIb decentralised trial to further assess the role of Airsupra in reducing the risk of asthma exacerbations. The Airsupra clinical co-development programme was funded by Blackstone Life Sciences, Royalty Pharma and Abingworth. Bradley E. Chipps, Past President of the American College of Allergy, Asthma & Immunology and Medical Director of Capital Allergy & Respiratory Disease Center in Sacramento, US, said: "People with asthma are at risk of severe exacerbations regardless of their disease severity or level of control. Current albuterol rescue inhalers alleviate acute symptoms, but do not treat the underlying inflammation in asthma. The approval of Airsupra means that, for the first time, adults with asthma in the US have a rescue treatment to manage both their symptoms and the inflammatory nature of their disease." Allison Jeynes, MD, Chief Executive Officer of Avillion, said: "We're delighted that our clinical co-development programme with AstraZeneca has been successful and that Airsupra has been approved in the US as a new treatment option for asthma patients. The Airsupra approval continues our 100% success rate facilitating clinical co-development programmes with pharma companies, demonstrating the strong value our innovative model can provide to partners and the excellence and dedication of our international team. We've had an excellent working relationship with AstraZeneca and are excited to continue our partnership with the BATURA Phase IIIb study, which is looking to continue building the evidence base of Airsupra to reduce the risk of asthma exacerbations." The full press announcement from AstraZeneca on the US approval of Airsupra can be found here. Notes Asthma Asthma is a chronic, inflammatory respiratory disease with variable symptoms that affects as many as 262 million people worldwide,4 including over 25 million in the US.5 Patients with asthma experience recurrent breathlessness and wheezing, which varies over time, and in severity and frequency.6 These patients are at risk of severe exacerbations regardless of their disease severity, adherence to treatment or level of control.7,8 There are an estimated 136 million asthma exacerbations globally per year,9 including 10 million in the US;5 these are physically threatening and emotionally significant for many patients11 and can be fatal.4,11 Inflammation is central to both asthma symptoms7 and exacerbations.12 Many patients experiencing asthma symptoms use a SABA (e.g. albuterol) as a rescue medicine;13-15 however, taking a SABA alone does not address inflammation, leaving patients at risk of severe exacerbations,16 which can result in impaired quality of life,17 hospitalisation18 and frequent oral corticosteroid (OCS) use.18 Treatment of exacerbations with as few as 1-2 short courses of OCS are associated with an increased risk of adverse health conditions including type 2 diabetes, depression/anxiety, renal impairment, cataracts, cardiovascular disease, pneumonia and fracture.19 International recommendations from the Global Initiative for Asthma no longer recommend SABA alone as the preferred rescue therapy.6 MANDALA, DENALI and the CREST (Combination REliever STudies) programme The CREST clinical trial programme studied the efficacy and safety of PT027 and included the MANDALA,1,20,21 DENALI2,22,23 and TYREE25 Phase III trials. MANDALA1,20,21 was a Phase III, randomised, double-blind, multicentre, parallel-group, event-driven trial evaluating the efficacy and safety of Airsupra compared to albuterol on the time to first severe asthma exacerbation in 3,132 adults, adolescents, and children (aged 4–11 years) with moderate to severe asthma taking ICS alone or in combination with a range of asthma maintenance therapies, including long-acting beta2-agonists (LABA), leukotriene receptor antagonists (LTRA), long-acting muscarinic antagonists (LAMA) or theophylline. The trial comprised a two-to-four-week screening period, at least a 24-week treatment period and a two-week post-treatment follow-up period. Patients were randomly assigned to one of the following three treatment groups in a 1:1:1 ratio: Airsupra 180/160mcg (excluding children aged 4–11 years), albuterol/budesonide 180/80mcg or albuterol 180mcg, taken as an as-needed rescue medicine. Airsupra and the albuterol comparator were delivered in a pMDI using AstraZeneca's Aerosphere delivery technology. The primary efficacy endpoint was the time to first severe asthma exacerbation during the treatment period. Secondary endpoints included severe exacerbation rate (annualised), total systemic corticosteroid exposure (annualised), asthma control and health-related quality of life. Results from the positive MANDALA Phase III trial showed that Airsupra demonstrated a statistically significant reduction in the risk of a severe exacerbation versus albuterol rescue in patients with moderate to severe asthma1,21. Compared with albuterol rescue, Airsupra at the 180mcg albuterol/160mcg budesonide dose reduced the risk of a severe exacerbation by 27% (p<0.001) in adults and adolescents1,21. Primary and secondary endpoint results in adults and adolescents1,21 (pre-planned on-treatment efficacy analysis) aDeterioration of asthma requiring use of SCS for ≥3 days, or inpatient hospitalisation, or emergency room visit, that required SCS. bBefore discontinuation of randomised treatment or change in maintenance therapy. CI, confidence interval; SCS, systemic corticosteroid; SD, standard deviation Primary endpoint results in adults, adolescents, and children1,21 (pre-planned on-treatment efficacy analysis) aDeterioration of asthma requiring use of SCS for ≥3 days, or inpatient hospitalisation, or emergency room visit, that required SCS. bBefore discontinuation of randomised treatment or change in maintenance therapy. CI, confidence interval Adverse events (AEs) were similar across the treatment groups in the trial and consistent with the known safety profiles of the individual components, with the most common AEs including nasopharyngitis and headache.1,22 DENALI2,23,24 was a Phase III, randomised, double-blind, placebo-controlled, multicentre, parallel-group trial evaluating the efficacy and safety of Airsupra compared to its components albuterol and budesonide on improvement in lung function in 1,001 adults, adolescents, and children aged 4–11 years with mild to moderate asthma previously treated either with SABA as-needed alone or in addition to regular low-dose ICS maintenance therapy. The trial comprised a two-to-four-week screening period, a 12-week treatment period and a two-week post-treatment follow-up period. Patients were randomly assigned to one of the following five treatment groups in a 1:1:1:1:1 ratio: Airsupra 180/160mcg four times daily (excluding children aged 4–11 years), albuterol/budesonide 180/80mcg four times daily, albuterol 180mcg four times daily, budesonide 160mcg four times daily (excluding children aged 4–11 years) and placebo four times daily. Airsupra, the albuterol and budesonide comparators and placebo were delivered in a pMDI using AstraZeneca's Aerosphere delivery technology. The dual primary efficacy endpoints were change from baseline in FEV1 area under the curve 0-6 hours over 12 weeks of Airsupra compared to budesonide to assess the effect of albuterol and change from baseline in trough FEV1 at Week 12 of Airsupra compared to albuterol to assess the effect of budesonide. Secondary endpoints included the time to onset and duration of response on day one, number of patients who achieved a clinically meaningful improvement in asthma control from baseline at Week 12 and trough FEV1 at Week 1. In the trial, Airsupra demonstrated a statistically significant improvement in lung function measured by forced expiratory volume in one second (FEV1), compared to the individual components albuterol and budesonide, and compared to placebo in patients with mild to moderate asthma aged 12 years or older. Onset of action and duration of effect were similar for Airsupra and albuterol. The safety and tolerability of Airsupra in DENALI was consistent with the known profiles of the components. About Avillion Avillion offers pharma partners an innovative model providing additional funding and clinical development expertise, to maximise the potential of new and existing assets. With deal sizes ranging from $50M–$600M, Avillion takes on the full clinical and regulatory risk, focusing on the speed and quality of trial execution. Typically supporting programs post proof-of-concept through to registration and with an agnostic approach to therapy area, Avillion prides itself in adding value around operational expertise while being backed by established long-term investors. Avillion was founded in 2012 and is backed by Abingworth and Blackstone Life Sciences (previously Clarus Ventures). The Airsupra clinical co-development programme was funded by Blackstone Life Sciences, Royalty Pharma and Abingworth. For more information, please visit us at References Papi A, et al. Albuterol–Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. N Engl J Med 2022; 386 (22): 2071-2083. Chipps BE, et al. Efficacy and safety of albuterol/budesonide (PT027) in mild-to-moderate asthma: Results of the DENALI study. Am J Respir Crit Care Med 2022; 205: A3414. Abstract. Available at: [Last accessed: November 2022]. Airsupra (albuterol/budesonide) US prescribing information; 2023. The Global Asthma Network. The Global Asthma Report 2022. [Online]. Available at: [Last accessed: November 2022]. CDC. Most Recent National Asthma Data. [Online]/ Available at: . [Last accessed: November 2022]. Global Initiative for Asthma. Global strategy for asthma management and prevention, 2022. Available at: . [Last accessed: November 2022]. Price D, et al. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014; 24: 14009. Papi A, et al. Relationship of inhaled corticosteroid adherence to asthma exacerbations in patients with moderate-to-severe asthma. J Allergy Clin Immunol Pract. 2018; 6 (6): 1989-98.e3. AstraZeneca Pharmaceuticals. Data on File. Budesonide/formoterol Data on File: Annual Rate of Asthma Exacerbations Globally. (REF-173201) Sastre J, et al. Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada. World Allergy Organ J. 2016; 9: 13. Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40 (4): 364-372. Wark PA, et al. Asthma exacerbations· 3: pathogenesis. Thorax. 2006; 61 (10): 909-15. Johnson DB, et al. Albuterol. 2022 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 29489143. Montemayor T, et al. Albuterol: Often Used and Heavily Abused. Respiratory Care November 2021, 66 (Suppl 10) 3603775 ClinCalc.com. Albuterol: Drug Usage Statistics, US 2013 – 2020. Available at: . [Last accessed: November 2022]. Nwaru BI, et al. Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2020; 55 (4): 1901872. Lloyd A, et al. The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK. Prim Care Respir J. 2007; 16 (1): 22-7. Bourdin A, et al. ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions. Eur Respir J. 2019; 54 (3): 1900900. Price DB, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018; 11: 193–204. Chipps BE, et al. Evaluation of the Efficacy and Safety of As-Needed PT027 Budesonide/Albuterol MDI) Compared to As-Needed Albuterol MDI in Adults and Children 4 Years of Age or Older with Uncontrolled Moderate to Severe Asthma: Design of the MANDALA Study. Am J Respir Crit Care Med. 2020; 201: A3015. Papi A, et al. Efficacy and safety of as-needed albuterol/budesonide versus as-needed albuterol in adults, adolescents and children aged ≥4 years with moderate-to-severe asthma: Results of the MANDALA study. American Thoracic Society International Conference 2022. Oral Presentation. Abstract A3413 during B93. BREAKTHROUGHS IN PEDIATRIC AND ADULT ASTHMA CLINICAL TRIALS Clinicaltrials.gov. A Study to Assess the Efficacy and Safety of Budesonide/Albuterol Metered-dose Inhaler (BDA MDI/PT027) Used 4 Times Daily in Adults and Children 4 Years of Age or Older With Asthma (DENALI). Available at . [Last accessed: November 2022]. AstraZeneca Pharmaceuticals. Data on File. DENALI clinical trial protocol Data on File (ID: 121792). LaForce C, et al. Albuterol/budesonide for the treatment of exercise-induced bronchoconstriction in patients with asthma: The TYREE study. Ann Allergy Asthma Immunol. 2022; 128: 169-177. SOURCE Avillion LLP

近日，美国生物制药公司Bellerophon Therapeutics公布了其独家脉冲一氧化氮输送系统——INOpulse用于治疗纤维化间质性肺病（fILD）的最新试验进展。研究中，患者的心肺功能水平通过INOpulse得到了显著提升。随后，Bellerophon申请开展治疗与结节病相关的肺动脉高压(PH-Sarc)的2期试验，并获得FDA批准。Bellerophon Therapeutic专注于开发创新疗法，目标是满足当前心肺疾病治疗中的医疗需求。该公司目前正计划开发INOpulse平台内的多个候选产品。该平台有望服务20万名fILD患者，并拥有价值超过10亿美元的潜在肺动脉高压（PH）和慢性阻塞性肺病（COPD）市场。 通过鼻插管针对性输送NO，书本大小供多场景使用 INOpulse通过输送装置和鼻插管将吸入式一氧化氮(iNO)直接输送到患者的肺部。当NO进入平滑肌细胞时，它会直接激活这些细胞中的可溶性鸟苷酸环化酶(sGC)。接着sGC又产生环磷酸鸟苷(GMP)，这种物质可以使平滑肌细胞松弛，从而帮助血管（动脉）扩张，降低肺部血压，减少右心室的压力。另外，INOpulse旨在以有针对性的方式输送NO，使其主要作用于肺功能良好的部分。由于NO对血红素蛋白的高亲和力，任何量的iNO在输送到肺部并到达血流后都会迅速与血红蛋白结合，从而消除全身血管扩张的可能性。 INOpulse设备轻巧便携，供患者每天在家中或户外使用：● 大小与一本平装书类似，重约1.1千克● 充满电后的电池寿命约为16小时● 简单直观的用户友好界面● 与许多通过鼻插管操作的长期氧疗系统兼容● 自动调整患者的呼吸模式，给予稳定和准确的剂量● 专有的三腔鼻插管，可以更将设定剂量精准输送给患者 INOpulse 图源：Bellerophon官网 三大管线覆盖超40亿美元PH市场 目前Bellerophon正在INOpulse平台内开发三种候选产品。第一个产品用于治疗纤维化间质性肺病(fILD)，已于近日进入3期试验。在此之前的研究中，通过INOpulse，患者肺血管阻力提高了21%，平均肺动脉压提高了12%。纤维化间质性肺病(fILD)作为间质性肺病（ILD）中较为严重的一种，会导致呼吸困难、肺功能下降、低氧症。美国fILD患者人数约为22.6万，其中约有30%-40%与肺动脉高压（PH）相关。PH是肺部血管（肺动脉）的高血压。它会使肺动脉壁无法扩张，因此血流难以通过，心脏右侧不能将血液泵入动脉，从而引发心脏衰竭。研究发现，带有fILD的PH会进一步降低患者生存率。在美国，伴有中高风险PH的fILD治疗市场价值超过20亿美元。另外，INOpulse针对慢性阻塞性肺疾病相关的肺动脉高压(PH-COPD)和与结节病相关的肺动脉高压(PH-Sarc)的治疗均已进入2期临床试验。数据显示，INOpulse可改善PH-COPD和PH-Sarc患者的血流动力学，且具有良好的耐受性。COPD是由慢性炎症、气道和肺组织损伤引起的慢性疾病。虽然COPD主要是一种呼吸系统疾病，但患者若长期接触烟草烟雾中的毒素可能会导致肺循环发生变化，从而引起慢性肺血管收缩和PH。美国COPD患者人数约为1270万，其中27%带有PH，其五年内生存率仅为37%。治疗市场价值超过10亿美元。Sarc的特征在于肺或淋巴组织中的炎性细胞（肉芽肿）的生长。症状包括疲劳、体重减轻、关节疼痛、眼睛干涩、膝盖肿胀、视力模糊、气短、干咳或皮肤损伤。美国约有20万SARC患者，其中30%带有PH，其五年内的生存率仅为59%。治疗市场价值超6过10亿美元。研发管线 图源：Bellerophon官网 六年内完成上亿美元融资，未来收入增长预计达80.5% Bellerophon前身为Ikaria Development，于2014年2月从Ikaria获得了开发和商业化INOpulse项目的全球独家权利。今天的Bellerophon已经是一个经验丰富的团队，专攻罕见病和呼吸道疾病领域。Bellerophon首席执行官兼首席监管、安全和质量官Peter Fernandes于2015年加入Bellerophon。在这之前，Fernandes在呼吸系统和心血管疾病领域拥有超过30年的全球开发经验，带领团队获得了许多知名药物的批准，如Flomax、Spiriva、Omnaris，还曾领导勃林格殷格翰美国呼吸和胃肠道药物监管事务小组。另外，Fernandes还担任肺血管研究所(PVRI)创新药物开发计划的联合主席，致力于与学术界、工业界和监管机构合作开发肺动脉高压(PH)的监管和临床试验设计。 2015年2月13日，Bellerophon完成首次公开募股，最终以每股12美元的价格发行了500万股股票。2017年，Bellerophon宣布出售约1940万股普通股和认股权证，总收益约2340万美元。本次投资者包括Puissance Capital Management和Venrock Healthcare Capital Partners等。2020年4月，Bellerophon宣布以每股12.00美元的价格完成约128万股普通股的发行，总收益为1530万美元。2020年5月22日，Bellerophon宣布结束其先前宣布的公开发售。本次Bellerophon以每股13.00美元的公开发行3,365,384股普通股，同时注册直接发售，总收益约为4370万美元。 Bellerophon将这些款项用于一般公司用途，包括研发、临床试验、制造以及行政费用。从2022年1月到6月，Bellerophon的研发费用为890万美元，而去年同期为680万美元。这一增长主要是由于正在进行的3期fILD试验。近日，FDA批准Bellerophon减少该试验的研究规模。此举使Bellerophon股价上涨24%（截至2022年11月10日收盘，股价报1.1美元）。分析师预测，Bellerophon在未来几年内的收入年均增长将会达到80.5%（美国市场平均年收入增长7%），利润年均增长将会达到30.7%（美国市场平均年利润增长13.3%）。 全球iNO市场复合年增长率8.04%，可探索空间巨大 2022年全球iNO市场价值约为8.0121亿美元，预计到2027年将达到11.7942亿美元，复合年增长率为8.04%。全球iNO市场分散，存在多个主要市场参与者，包括：液化空气公司、Bellerophon Therapeutics、BOC Healthcare、Beyond Air、Praxair、Vero Biotech等。这些供应商专注于研发活动，以开发先进的创新产品并加强其产品组合。为了保持竞争力并获得主要市场收入，他们还通过其强大的分销渠道及其子公司在全球销售和分销其产品。从2022年至2027年，北美地区将在全球iNO市场保持领先定位，占据全球31%的市场份额。其促进因素包括大量的供应商、发达的医疗保健部门以及呼吸道疾病患病率的上升。在此期间，主要消费地区有美国、中国、印度、德国和英国。 全球iNO市场可细分为：新生儿呼吸治疗、慢性阻塞性肺病(COPD)、急性呼吸窘迫综合征(ARDS)等。其中新生儿呼吸治疗在全球iNO市场中占比最大。这是因为新生儿疾病患病率上升，例如持续性肺动脉高压（PPHN）和新生儿缺氧性呼吸衰竭(HRF)。由于iNO疗法在过去的成功应用，相关的研究和开发活动近年来有所增加，包括利用iNO治疗成人镰状细胞病、支气管肺发育不良和疟疾。另外，呼吸道感染、肿瘤预防等领域还存在着巨大的发展空间供市场参与者探索。例如，目前尚无药物获批治疗患有急性毛细支气管炎的新生儿，而这却是全球最常见的新生儿疾病之一。 内容来源于网络，如有侵权，请联系删除。