AXON Neuroscience SE ("Axon"), an industry leading, clinical stage biotech at the forefront of treatment and prevention of Alzheimer's disease, has today announced the results of the Phase II trial for AADvac1, its first-in-class vaccine to slow down the progression of Alzheimer's Disease.
The Phase II ADAMANT trial was designed as a randomized, double-blinded, placebo- controlled trial in mild Alzheimer's Disease. The primary objective was safety, with secondary objectives to evaluate immunogenicity, efficacy on clinical outcomes and key biomarkers. Axon studied AADvac1 on 196 patients in eight European countries over 24 months, in order to prove the concept of disease modifying effect of the vaccine and to inform the design of future confirmatory studies.
Phase II trial – headline findings
For the primary endpoint, the ADAMANT trial showed that AADvac1 has proven to be safe and well tolerated, with no difference in the incidence and nature of adverse events between the treatment and placebo groups. No other safety signals emerged from any other safety or medical assessments. This confirms the overall benign safety profile of AADvac1, demonstrated in prior clinical trials.
Axon's vaccine is an immunotherapy, harnessing the body's immune system to produce specific antibodies. In the Phase II trial, the treatment was shown to be highly effective in inducing a robust immune response, with 98.2% of patients generating antibodies against pathological tau. The finding is consistent with previous observations in the Phase I trial and support excellent immunogenicity in this population.
A highly statistically significant impact was seen on neurodegeneration and neuronal loss, as measured in blood by Neurofilament Light Chain ("NfL"). It showed a marked slow-down of the expected increase of NfL in the patients treated with AADvac1, demonstrating a 12.6% change from baseline over two years versus 27.7% for patients on placebo (p value = 0.0039). This indicates that AADvac1 slows the progression of the neurodegenerative process to levels that are more typically seen in healthy individuals.
NfL is a biomarker to track and monitor effects on neurodegeneration in patients with Alzheimer's Disease, Multiple Sclerosis and other neurological disorders.
Compelling trends were observed in the reduction of three separate cerebrospinal fluid ("CSF") Alzheimer's Disease specific biomarkers in treated patients, including two variants of pathological tau (phospho-Tau181 and phospho-Tau217). Despite of a smaller sample size of patients providing required lumbar punctures, the shown effect sizes were large to moderate. This strongly suggests that AADvac1 is successful in slowing the progression of tau pathology.
Positive signals for cognitive endpoints were observed among younger populations in the Phase II trial. These were showed on clinical outcome measure CDR-SB and consistently further across a wide range of additional endpoints including MMSE, ADCS-MCI-ADL, MRI brain volumetry and DTI.
Clinical Dementia Rating – Sum of Boxes, Mini Mental State Examination and Activities of Daily Living are widely accepted clinical outcome measures to asses cognitive and functional decline in Alzheimer's Disease, while Magnetic Resonance Imaging and Diffusion Tensor Imaging are biomarkers that track the level of brain atrophy and damage, which are associated with the progression of the disease.
Plans for future studies
Based on the extensive learnings and positive data generated by the Phase II ADAMANT trial, Axon is moving ahead with plans for the upcoming clinical development. Axon is now seeking an experienced, global partner to help plan and conduct the next phase of clinical trials in order to rapidly bring the benefits of the therapy to a wide ranging and growing patient population.
Quote from Michal Fresser, CEO of Axon Neuroscience, said:
"Today's results mark an important milestone for Axon, and for the entire population of the world that suffers from this devastating disease. Our vaccine is the first to solely target pathological tau proteins, which drive the cognitive decline and memory loss seen in Alzheimer's. These results, which strongly reveal a disease-modifying effect on the disease, underpin our confidence to take the next steps in bringing a life-changing treatment to patients as soon as possible."
Members of Axon's Scientific Advisory Board, said:
"I am excited to see that AADvac1 is safe and well tolerated and shows impact on the neurodegenerative process of Alzheimer's Disease. The positive trends on both clinical and biological measures give me hope that this treatment brings benefit to patients in the future."
- Philip Scheltens (Professor of Cognitive Neurology and Director of the Alzheimer Centre at the Amsterdam University Medical Centre, Chairman of the Scientific Advisory Board of Axon.)
"Since AADvac1 targets pathological tau, I am truly impressed by the downstream effect on neurodegeneration indicated by the neurofilament findings. This effect, observed for the very first time in an Alzheimer's trial, is a significant and much needed boost for the industry."
- Kaj Blennow (Head of Research on Neurochemical Pathogenesis and Diagnostics at the University of Gothenburg. He has pioneered the development of CSF and blood biomarkers for Alzheimer's disease.)
The Axon Story
Axon Neuroscience was founded in 1999 and is now the single biggest team in the world dedicated exclusively to tau research in relation to treating Alzheimer's Disease, with over 60 scientists and 15 senior scientific leaders.
Axon was founded by Professor Michal Novak, who started his research in the late 1980s at Cambridge with Nobel Laureates Klug, Milstein and Walker, discovering tau as the structural constituent of neurofibrillary tangles, a major hallmark of Alzheimer's disease. He was the first to make the link between pathological changes of tau and Alzheimer's disease, proposing tau as a valid target. Professor Novak and Axon have since pioneered the implementation of tau therapy.
Alzheimer's Disease has been growing in prominence globally ever since it was first identified in 1906. Currently 35 million people suffer from Alzheimer's worldwide; it is the 6th leading cause of death in the US; and is set to almost double in 20 years.
Axon Neuroscience's vaccine AADvac1 has the potential to be a huge scientific breakthrough for humankind, meeting one of the world's most critical unmet medical needs.
About Axon Neuroscience
Axon Neuroscience is on a mission to eradicate Alzheimer's disease by developing tau-based treatments, which shall halt the disease and relieve the symptoms in sufferers, as well as prevent the onset in potential victims.
Axon was founded in 1999 by Professor Michal Novák, who started his research in the late 1980s at Cambridge with Nobel Laureates Klug, Milstein and Walker, discovering tau as the structural constituent of neurofibrillary tangles, a major hallmark of Alzheimer's disease. He was the first to make the link between pathological changes of tau and Alzheimer's disease, proposing tau as a valid target. Professor Novak and Axon have since pioneered the implementation of tau therapy.
The company has a scientific team of over 60 scientists and 15 senior scientific leaders, with over 500 cumulative years' experience in Alzheimer's, is the single biggest team in the world dedicated exclusively to tau research for over 20 years.
About Tau and Tau vaccine AADvac1
Tau proteins play a vital role in the healthy, normal functioning of a brain. The disease starts when normal tau proteins become pathological by truncation (i.e. the process of pathological truncation makes them 'unhealthy' – completely changing their structure and function). Unhealthy tau are prone to attaching to each other, creating clumps which spread through the brain, causing the disease. The distribution of these clumps shows strong correlation with clinical symptoms in patients.
Axon has developed a vaccine AADvac1, which is the most clinically-advanced tau therapy in development. It uses the body's own immune system to induce the production of antibodies that specifically target unhealthy tau.
It differs from other tau-based research by tackling both the formation of 'unhealthy' tau clumps and the spread of those clumps already formed. The rest of the industry has been focused primarily on the latter. In addition AADvac1 has been proven to successfully discriminate between normal and unhealthy tau, ensuring only the latter are targeted. In this way, Axon's treatment is more accurate and safer.
Axon's vaccine can tackle Alzheimer's disease even in its pre-symptomatic stages, which can start 10 to 20 years prior to the onset of first clinical symptoms – this is a potentially life-changing prevention for patients who would otherwise be destined to suffer at the hands of Alzheimer's.
AXON NeuroscienceSE (" Axon ")，一个在治疗和预防阿尔茨海默病前沿处于临床阶段的生物技术领先的行业，今天宣布了 AADvac1的 II 期试验结果，它的一流疫苗，以减缓阿尔茨海默病的进展。
II 期 ADAMANT 试验设计为一项随机、双盲、安慰剂对照试验，用于治疗轻度老年痴呆症。首要目标是安全性，次要目标是评价免疫原性、临床疗效和关键生物标志物。Axon 在24个月内对8个欧洲国家的196名患者进行了 AADvac1的研究，以验证疫苗的疾病改变效应的概念，并为未来的验证性研究的设计提供参考。
对于主要终点， ADAMANT 试验表明， AADvac1已被证明是安全和良好的耐受性，治疗和安慰剂组之间的不良事件发生率和性质没有差异。任何其他安全或医疗评估均未出现其他安全信号。这证实了 AADvac1的整体良性安全性，在以前的临床试验中得到了证实。
Axon 的疫苗是一种免疫疗法，利用人体免疫系统产生特异性抗体。在 II 期试验中，该疗法被证明是非常有效的诱导一个强大的免疫反应，98.2%的患者产生抗体的病理 tau 。这一发现与第一阶段试验中的先前观察结果一致，并支持这一人群的优秀免疫原性。
用神经纤维光链（ NfL ）测量血液中的神经变性和神经元损失，具有高度统计学意义。结果显示，在接受 AADvac1治疗的患者中， NfL 的预期增长明显放缓，与基线相比，两年间的变化为12.6%，而安慰剂组的变化为27.7%（ p 值=0.0039）。这表明 AADvac1将神经退行性过程的进展减慢到健康个体更常见的水平。
在接受治疗的患者中，三种不同的脑脊液(“ CSF ”)阿尔茨海默病特异性生物标志物的减少，包括两种病理 tau 变体(磷牛 Tau181和磷牛 Tau217)。尽管提供所需腰椎穿刺的病人样本较小，但所显示的效果大小是大到中等的。这强烈表明 AADvac1在减缓 tau 病理进展方面是成功的。
在 II 期试验中，年轻人群的认知端点出现阳性信号。这些指标在临床结果测量 CDR-SB 上显示，并且在包括 MMSE 、 ADCS-MCI-ADL 、 MRI 脑容量测量和 DTI 在内的更多终点上持续地更远。
基于广泛的学习和 II 期 ADAMAANT 试验产生的积极数据， Axon 正在推进即将到来的临床开发计划。安盛目前正在寻求一个有经验的全球合作伙伴，帮助规划和进行下一阶段的临床试验，以便迅速将治疗的好处，以广泛和不断增长的患者群体。
Axon Neuroscience 首席执行官 Michal Fresser 的引述说：
“今天的结果是 Axon 的一个重要里程碑，也是全世界遭受这种毁灭性疾病的所有人的一个重要里程碑。我们的疫苗是第一个专门针对病理牛蛋白，这驱动认知能力下降和记忆丧失看到阿尔茨海默氏症。这些结果有力地揭示缓解疾病药物疾病对疾病的影响，巩固了我们采取下一步措施尽快为患者提供改变生命的治疗的信心。”
- Philip Scheltens (阿姆斯特丹大学医学中心认知神经学教授和阿尔茨海默病中心主任， Axon 科学咨询委员会主席)
“由于 AADvac1的目标是病理 tau ，我真正印象深刻的下游影响，神经纤维的发现表明神经退化。这是阿尔茨海默氏症试验中首次观察到的结果，对该行业来说是一项重大且非常必要的推动。”
- Kaj Blennow （哥德堡大学神经化学病理学和诊断研究主任，他率先开发了用于阿尔茨海默病的 CSF 和血液生物标记物。）
Axon Neuroscience 成立于1999年，目前是全球最大的一支专注于 tau 研究治疗阿尔茨海默氏症的团队，拥有60多名科学家和15名高级科学领导人。
Axon 是由 Michal Novak 教授创立的，他于20世纪80年代末在剑桥与诺贝尔奖得主 Klug 、 Milstein 和 Walker 共同开展研究，发现 tau 是神经纤维缠结的结构成分，神经纤维缠结是阿尔茨海默病的主要特征。他是第一个将 tau 的病理变化与阿尔茨海默病联系起来的人，他建议 tau 作为一个有效的靶点。诺瓦克教授和 Axon 教授已经率先实施 tau 疗法。
Axon Neuroscience 公司的 AADvac1疫苗有可能成为人类的巨大科学突破，满足世界上最关键的尚未得到满足的医疗需求之一。
Axon Neuroscience 的使命是通过开发基于 tau 的治疗方法来根除阿尔茨海默病，这种治疗方法可以阻止该病的发生，缓解患者的症状，并防止潜在的受害者出现。
Axon 于1999年由 Michal Nova @k 教授创立，他于20世纪80年代末在剑桥与诺贝尔奖得主 Klug 、 Milstein 和 Walker 共同开展研究，发现 tau 是神经纤维缠结的结构成分，神经纤维缠结是阿尔茨海默病的主要特征。他是第一个将 tau 的病理变化与阿尔茨海默病联系起来的人，他建议 tau 作为一个有效的靶点。诺瓦克教授和 Axon 教授已经率先实施 tau 疗法。
牛蛋白在大脑健康、正常的功能中起着至关重要的作用。当正常的 tau 蛋白通过截断而成为病理时（例如，病理截断过程使它们“不健康”——完全改变了它们的结构和功能）。不健康的牛磺酸容易相互附着，形成丛状，通过大脑传播，导致疾病。这些团块的分布与临床症状有很强的相关性。
Axon 公司研发了一种疫苗 AADvac1，这是临床上最先进的 tau 治疗方法。它利用人体自身的免疫系统诱导产生针对不健康牛头的抗体。
它与其他基于 tau 的研究不同，它既解决了“不健康” tau 丛的形成，也解决了已经形成的那些丛的扩散问题。其他行业主要集中在后者。此外， AADvac1已被证明成功地区分了正常和不健康的牛头，确保只有后者的目标。这样， Axon 的治疗更加准确和安全。