Interferon beta 1a(The University of Southampton)

曾经一度被寄予厚望的新冠特效药，在全球疫情逐渐消退的当下，却接连爆出“翻车”的消息。近日，默沙东发布了Molnupiravir两项真实世界临床证据和一项非临床研究进展结果。其中一项由牛津大学资助的开放、前瞻性真实世界PANORAMIC的研究数据初步分析结果显示，在英国进行的针对＜65岁接种疫苗的成年人中，就减少住院人数和死亡人数方面而言，Molnupiravir添加到常规护理与仅使用常规护理相比没有任何差异，到第28天的住院和死亡的发生率，两组均为0.8%。通俗地说，这药吃了个寂寞，和安慰剂没有任何差别。Molnupiravir是全球首款获得授权的口服抗新冠病毒药物，属于新型核糖核苷类似物前药，用于治疗经SARS-CoV-2检测呈阳性、确诊轻度至中度新冠病毒病（新冠肺炎）、且有潜在重症（包括住院或死亡）风险的成年患者。这款由默沙东研发上市的抗新冠药物，已经在全球超过40多个国家和地区上市，就在9月28日，默沙东与国药集团签署协议，将Molnupiravir在中国的经销权和独家进口权授予国药集团。全球另一款抗新冠病毒的明星药物，由辉瑞研发上市的Paxlovid，也发现了疗效欠佳的临床证据。今年8月，在《新英格兰医学杂志》上发表的一项研究显示，对于40-60岁的患者来说，在接受Paxlovid治疗与不接受Paxlovid治疗的患者中，住院率为每10万人15.2例VS每10万人15.8例，二者相差并不大。但是研究也显示，Paxlovid对老年人确实有一定效果。具体来说，在参与研究的4.3万名65岁以上的新冠患者中，接受Paxlovid治疗的患者住院率为每10万人14.7例，而在未经治疗的患者住院率每10万人58.9例。此外，对Paxlovid还有另外一个更严重的质疑，就是一些患者在停药后，新冠症状出现了反弹，比如包括美国总统拜登、辉瑞CEO艾伯乐在内，都曾在服药后发生了“复阳”症状。除了以上两款已上市的知名药物开始“爆雷”以外，几款正在研发中的抗新冠病毒药物也纷纷传出坏消息。10月15日，日本富士胶片公司正式对外宣布，已决定停止研发其新冠治疗药物Avigan(法匹拉韦)，原因是在对患者的临床试验中未能确认药物的有效性，以及重症率较低的Omicron毒株成为主流，令口服药的需求急剧减少。富士胶片从去年4月展开法匹拉韦的临床试验，原先目标是招募316名患者，但直至今年3月为止，只有84名患者进入临床试验，而且分析了受试者的数据后，显示法匹拉韦未能对预防重症产生有意义的效用。在今年更早的2月21日，美国Synairgen公司也宣布，SNG001治疗新冠肺炎住院患者的临床III期SPRINTER研究，未达到其主要或关键次要疗效终点，宣告研发失败。受此消息影响，Synairgen公司股价下跌84%。关于已获批药物上市后表现不佳，以及在研药物的失败，学术界有多种解释，主要的原因集中在新冠病毒株的变异；有专家指出，以病毒的某个单分子为靶点的小分子口服药对付不断变异的病毒，出现力不从心、效力欠佳的情况可以说是必然的。如果抗新冠病毒小分子药物的时效性如此之短，甚至在药物上市的时刻，就是治疗效力开始大幅衰减的时刻，那么抗新冠病毒小分子药物的临床意义，可能要大打折扣。目前全球已有4款新冠口服药上市，其中真实生物的阿兹夫定和辉瑞的Paxlovid两款药物，已经在中国获批上市。此外还有礼来和Incyte的巴瑞替尼老药新用，用于需要补充氧的新冠患者，于2021年4月在日本上市，在美国获批EUA；默沙东的莫奈拉韦最早于2021年11月在英国获批上市，随后在日本上市、在美国获批EUA，目前已向中国提交NDA。再看中国市场，目前虽然只有真实生物的阿兹夫定一款国产药物获批，但是国内还有一支浩浩荡荡的新冠特效药研发大军，包括：君实生物、云顶新耀、先声药业、歌礼制药、科兴制药、开拓药业、盟科药业、众生睿创、盘龙药业、广生中霖、广生堂，等等。希望他们可以创造奇迹。来源 | 医药投资部落（药智网获取授权转载）撰稿 | 医药投资部落责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。— Tips —如果您有医药行业相关的线索或对医药政策、研发创新、资本市场、产业发展有深度观察欢迎投稿给我们马老师 18323856316（同微信）邮箱：maxuelian@yaozh.com发现“分享”和“赞”了吗，戳我看看吧

Fewer participants treated with SNG001 compared to placebo progressed to hospitalisation (1/110 vs 7/110, P=0.07) SNG001 was well-tolerated with a favourable safety pro with previous studies High level of adherence to SNG001 treatment at-home was observed, with 90% of patients completing all doses of the once-daily regimen SOUTHAMPTON, England--(BUSINESS WIRE)-- Synairgen plc (LSE: SNG), the respiratory company developing SNG001, an investigational formulation for inhalation containing the broad-spectrum antiviral protein interferon beta to treat or prevent severe viral lung infections, today announces topline data for participants treated with SNG001 in the US National Institutes of Health (NIH)/ AIDS Clinical Trials Group (ACTG)-led ACTIV-2 Phase 2 adaptive platform trial for COVID-19. Between February and August 2021, 221 symptomatic, non-hospitalised adult participants with COVID-19 were enrolled in the Phase 2 SNG001 evaluation and randomised between active drug (N=110 treated) and placebo (N=110 treated1), across 25 US sites. There were no statistically significant differences between SNG001 and placebo with respect to the primary outcomes of safety (SNG001 was well-tolerated), symptom resolution, or virology. Fewer participants required hospitalisation following treatment with SNG001 (N=1/110, [1%]) compared to placebo (N=7/110, [6%]), an 86% relative risk reduction, that was not statistically significant (P=0.07; two-sided Fisher’s exact test). There were no deaths in either arm. There were 13 participants with treatment-emergent Grade 3 or higher Adverse Events (AE) with four on SNG001 [3.6%] and nine on placebo [8.2%]. Based on the study results, the Independent Data Safety Monitoring Board for ACTIV-2 recommended SNG001 advance from Phase 2 into Phase 3 in the ACTIV-2 trial in October 2021. Later, in March 2022, the NIH decided to halt all participant recruitment in the trial due to the significant shift in the nature of the pandemic which would necessitate a substantial modification of the study design which was not feasible in a multiple treatment-arm platform trial of this size. Richard Marsden, CEO of Synairgen, commented: “The data from the ACTIV-2 trial in the US showing a non-significant but encouraging 86% relative risk reduction in hospitalisation following treatment with SNG001 in home-based patients are very interesting when considered in the context of therapeutic options for the management of non-hospitalised patients during a pandemic. “These results are really encouraging and build upon the strong body of non-clinical and clinical evidence, which includes Synairgen’s home-based trial (SG016) in high-risk patients,2 supporting SNG001’s potential as a broad-spectrum antiviral for a wide range of severe lung infections including COVID-19. We will now begin to evaluate the full data set and factor these findings into our development plans.” William Fischer, M.D., University of North Carolina (UNC), a lead investigator of SNG001 said: “These results, including a decrease in hospitalisations and adverse events among participants who received SNG001, are promising and warrant further investigation in a larger Phase 3 clinical trial. SNG001 is the first nebulized inhaled therapeutic to demonstrate promising results and, if confirmed in larger studies, could represent a potential treatment option for people who have COVID-19 but are not hospitalised.” Participants self-administered SNG001 or placebo via a nebuliser at home to complete 14 daily doses, with the first dose taken either at the study site or at home, with instructions provided by study staff and through an instructional video available online on how to take the study medication. There was a high level of adherence to the once-daily treatment in patients taking SNG001, with 90% of patients receiving full treatment. The ability to self-administer is important in the context of a pandemic when the ability of infected patients to travel to a clinic may be very challenging. The primary goals of the trial were to evaluate safety, to see if the investigational therapeutic could reduce the duration of symptoms through study day 28, and to see if the investigational therapeutic could increase the proportion of patients with undetectable virus in nasopharyngeal swabs at specific time points. Synairgen continues to actively pursue and refine multiple clinical approaches including company- and investigator-sponsored studies and possibly platform studies (as and when appropriate), to confirm the most expeditious clinical development path for SNG001 in patients hospitalised due to a severe viral lung infection including SARS-CoV-2, influenza, RSV, adenovirus, parainfluenza and rhinoviruses. This announcement reports on the reduction in hospitalisations, a key endpoint for determining efficacy of antivirals for COVID-19. Full results, including other key endpoints, will be presented and/or published by the NIH in due course. This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014. Notes for Editors About Synairgen Synairgen is a UK-based respiratory company focused on drug discovery, development and commercialisation. The Company’s primary focus is developing SNG001 (inhaled interferon beta) for the treatment of severe viral lung infections, including COVID-19, as potentially the first host-targeted, broad-spectrum antiviral treatment delivered directly into the lungs. SNG001 has been granted Fast Track status from the US Food and Drug Administration (FDA). Founded by University of Southampton Professors Sir Stephen Holgate, Donna Davies and Ratko Djukanovic in 2003, Synairgen is quoted on AIM (LSE: SNG). For more information about Synairgen, please see . About SNG001 SNG001 is a pH-neutral formulation of interferon-beta (IFN-beta) for inhalation that is delivered directly into the lungs using a mesh nebuliser, which the Company is developing as a potential host-directed antiviral treatment for patients hospitalised with severe viral lung infections, including COVID-19. SNG001 has broad potential applicability for patients hospitalised with respiratory symptoms due to viral infections such as SARS-CoV-2, influenza, RSV, adenovirus, parainfluenza and rhinoviruses. Viruses have been shown to suppress the production of IFN-beta, a naturally occurring protein that orchestrates the body's antiviral defences, with the aim of evading host immune responses. By administering IFN-beta into the lungs, the aim is to correct this deficiency, potentially switching back on the lungs' antiviral pathways to clear the virus. SNG001 has been shown to demonstrate potent in vitro antiviral activity against a broad range of viruses at concentrations that are achievable following inhaled delivery of SNG001 including RSV, rhinovirus, various influenza strains including H5N1, MERS-CoV and SARS-CoV-2 including Alpha, Beta, Gamma, Delta and Omicron variants of concern. About ACTIV-2 Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) was a public-private partnership to develop a coordinated research strategy to accelerate the development of the most promising COVID-19 treatments and vaccines (Protocol ACTIV-2/A5401; "Adaptive Platform Treatment Trial for Outpatients with COVID-19 (Adapt out COVID)"). ACTIV-2 is an adaptive Phase 2/3 trial testing agents in non-hospitalised adults experiencing mild to moderate COVID-19 sponsored by NIAID, part of the National Institutes of Health, and is led by the NIAID-funded AIDS Clinical Trials Group (ACTG). 1 One participant randomized to placebo did not receive study intervention and was excluded from all analyses. The treated population therefore included 220 participants (110 SNG001, 110 placebo). 2 Synairgen conducted a trial of SNG001 in high-risk, home-based COVID-19 patients (SG016) in which fewer patients treated with SNG001 were hospitalised (0/56) compared to placebo (2/58). In total across SG016 and ACTIV-2, 1/165 SNG001-treated home-based COVID-19 patients have been hospitalised.