Breaking News
December 13, 2018 - Paternal grandfather’s access to food associated with grandson’s mortality risk
December 13, 2018 - Our brain senses angry voices in a flash, study shows
December 13, 2018 - PM2.5 Exposure Linked to Asthma Rescue Medication Use
December 13, 2018 - Can’t exercise? A hot bath may help improve inflammation, metabolism, study suggests
December 13, 2018 - Can artificial intelligence help doctors with the human side of medicine?
December 13, 2018 - Virginia Tech and UC San Diego researchers team up to develop nonopioid drug for chronic pain
December 13, 2018 - NIH offers support for HIV care and prevention research in the southern United States
December 12, 2018 - Activating brain region could revive the urge to socialize among opioid addicts
December 12, 2018 - Relationship impairment appears to interfere with seeking mental health treatment in men
December 12, 2018 - Sleep, Don’t Cram, Before Finals for Better Grades
December 12, 2018 - Effective treatments for urticarial vasculitis
December 12, 2018 - Gun violence is a public health issue: One physician’s story
December 12, 2018 - The Science of Healthy Aging
December 12, 2018 - Yes to yoghurt and cheese: New improved Mediterranean diet
December 12, 2018 - Researchers uncover a number of previously unknown insecticide resistance mechanisms
December 12, 2018 - Regulating the immune system’s ‘regulator’
December 12, 2018 - In breaking bad news, the comfort of silence
December 12, 2018 - Study finds upward link between alcohol consumption and physical activity in college students
December 12, 2018 - FDA issues warning letter to Zhejiang Huahai Pharmaceutical involved in valsartan recall
December 12, 2018 - Presence of antiphospholipid antibodies tied to first-time MI
December 12, 2018 - DNA analysis finds that stethoscopes are teaming with bacteria
December 12, 2018 - New study could help inform research on preventing falls
December 12, 2018 - Women and men with heart attack symptoms receive different care from EMS
December 12, 2018 - Disrupted biological clock can contribute to onset of diseases, USC study shows
December 12, 2018 - New publications generate controversy over the value of reducing salt consumption in populations
December 12, 2018 - New data from TAILORx trial confirms lack of chemo benefit regardless of race or ethnicity
December 12, 2018 - Specific class of biomarkers can accurately indicate the severity of cancer
December 12, 2018 - Meds Taken Do Not Vary With ADL Impairment in Heart Failure
December 12, 2018 - Long-term study shows that HIV-2 is deadlier than previously thought
December 12, 2018 - People living near oil and gas wells show early signs of cardiovascular disease
December 12, 2018 - IONTAS founder and pioneer in phage display technology attends Nobel Prize Award Ceremony
December 12, 2018 - People who eat red meat have high levels of chemical associated with heart disease, study finds
December 12, 2018 - New method uses water molecules to unlock neurons’ secrets
December 12, 2018 - Genetics study offers hope for new acne treatment
December 12, 2018 - New computer model predicts prostate cancer progression
December 12, 2018 - Nobel Laureates lecture about immune checkpoint therapy for cancer treatment
December 12, 2018 - More Illnesses From Tainted Romaine Lettuce Reported
December 12, 2018 - Aspirin could reduce HIV infections in women
December 12, 2018 - The EORTC Brain Tumor Group and Protagen AG collaborate to study immuno-competence of long-term glioblastoma survivors
December 12, 2018 - Insights into magnetotactic bacteria could guide development of biological nanorobots
December 12, 2018 - Sacrificial immune cells alert body to infection
December 12, 2018 - Low-salt diet may be more beneficial for females than males
December 12, 2018 - Major soil organic matter compound battles chronic wasting disease
December 12, 2018 - Findings may open up new ways to treat dwarfism and other ER-stress-related conditions
December 12, 2018 - New computational model provides clearer picture of shape-changing cells’ structure and mechanics
December 12, 2018 - 10 Facts on Patient Safety
December 12, 2018 - Poorest dying nearly 10 years younger than the rich in ‘deeply worrying’ trend for UK
December 12, 2018 - Innovative care model for children with ASD reduces use of behavioral drugs in ED
December 12, 2018 - Spending time in and around Hong Kong’s waters linked to better health and wellbeing
December 12, 2018 - Simple measures to prevent weight gain over Christmas
December 12, 2018 - Research advances offer hope for patient-tailored AML treatment
December 12, 2018 - Researchers discover a ‘blind spot’ in atomic force microscopy
December 12, 2018 - Sprayable gel could help prevent recurrences of cancer after surgery
December 12, 2018 - SLU researchers explore how fetal exposure to inflammation can alter immunity in newborns
December 12, 2018 - How do patients want to discuss symptoms with clinicians?
December 12, 2018 - Zinc chelation may be able to deliver drug to insulin-producing cells
December 12, 2018 - Brigham researchers develop automated, low-cost tool to predict a woman’s ovulation
December 12, 2018 - Some people with Type 2 diabetes may be testing their blood sugar more often than needed
December 12, 2018 - Slow-growing type of glioma may be vulnerable to immunotherapy, suggests study
December 12, 2018 - Study provides new information regarding microRNA function in cellular homeostasis of zebrafish
December 12, 2018 - Study provides new understanding of mysterious ‘hereditary swelling’
December 12, 2018 - Researchers shed new light on how to combat Shiga and ricin toxins
December 12, 2018 - Pregnant Women Commonly Refuse Vaccines
December 12, 2018 - Drug treatment could offer new hope for some patients with brain bleeding
December 12, 2018 - Health care financial burden of animal-related injuries is growing, study says
December 12, 2018 - Macrophage cells could help repair the heart following a heart attack, study finds
December 12, 2018 - Researchers develop new system for efficiently producing human norovirus
December 12, 2018 - New artificial intelligence-based system to differentiate between different types of cancer cells
December 11, 2018 - Brazilian professors propose guidelines for therapeutic use of melatonin
December 11, 2018 - Healthy Lifestyle Lowers Odds of Breast Cancer’s Return
December 11, 2018 - New research identifies two genes linked to serious congenital heart condition
December 11, 2018 - NIH Director talks science, STEM careers with preteens
December 11, 2018 - Disabling a Cellular Antivirus System Could Improve Gene Therapy
December 11, 2018 - New tool swiftly provides accurate measure of patients’ cognitive difficulties
December 11, 2018 - NICE releases new guidelines for diagnosis and management of COPD
December 11, 2018 - Without Obamacare penalty, think it’ll be nice to drop your plan? Better think twice
December 11, 2018 - Researchers capture high-resolution X-ray and NMR image of key immune regulator
December 11, 2018 - Natural flavonoid is effective at treating leishmanisis infections, study shows
December 11, 2018 - Avoidant grievers unconsciously monitor and block mind-wandering contents, study shows
December 11, 2018 - Study identifies how hantaviruses infect lung cells
Eisai and Biogen Announce Detailed Results of Phase II Clinical Study of BAN2401 in Early Alzheimer’s Disease at Alzheimer’s Association International Conference (AAIC) 2018

Eisai and Biogen Announce Detailed Results of Phase II Clinical Study of BAN2401 in Early Alzheimer’s Disease at Alzheimer’s Association International Conference (AAIC) 2018

image_pdfDownload PDFimage_print

TOKYO and CAMBRIDGE, Mass., July 25, 2018 (GLOBE NEWSWIRE) — Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq:BIIB) (Headquarters: Cambridge, Massachusetts, United States, CEO: Michel Vounatsos, “Biogen”) announced detailed results from the Phase II study (Study 201) with BAN2401, an anti-amyloid beta (Aβ) protofibril antibody, in 856 patients with early Alzheimer’s disease as part of Session DT-01 “Recent Developments in Therapeutics” (Presentation number: DT-01-07) at the Alzheimer’s Association International Conference (AAIC) 2018 being held in Chicago, Illinois, United States on July 25. This abstract was accepted for Late Breaking oral presentation at AAIC.

Study 201 (ClinicalTrials.gov identifier NCT01767311) is a placebo-controlled, double-blind, parallel-group, randomized Phase II clinical study in 856 patients with mild cognitive impairment (MCI) due to Alzheimer’s disease or mild Alzheimer’s dementia (collectively known as early Alzheimer’s disease) with confirmed amyloid pathology in the brain. Patients were randomized to five dose regimens, 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly and 10 mg/kg biweekly, or placebo. This study used a Bayesian Adaptive Randomization Design to automatically allocate newly enrolled patients into the study to treatment arms showing higher probability of efficacy based on the results of interim analyses.

The study assessed changes from baseline to 18 months in biomarkers measuring the underlying disease pathophysiology, including changes in amyloid accumulated in the brain as measured by amyloid PET (positron emission tomography). The clinical endpoints of Alzheimer’s Disease Composite Score (ADCOMS), Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Sum of Boxes (CDR-SB) were also assessed from baseline to 18 months of treatment.

Through Bayesian interim analyses, the highest doses of 10 mg/kg monthly and 10 mg/kg biweekly were determined to be the treatment dosages with higher efficacy early in the trial, and as a result, the proportion of patients allocated to these treatment arms was greater (placebo: 247 patients, 2.5 mg/kg biweekly: 52 patients, 5 mg/kg monthly: 51 patients, 5 mg/kg biweekly: 92 patients, 10 mg/kg monthly: 253 patients, 10 mg/kg biweekly: 161 patients). Following a regulatory request (outside of the United States) in July 2014, the allocation of APOE4 carriers to the 10 mg/kg biweekly treatment arm was restricted, resulting in fewer APOE4 carriers in this arm and more patients being allocated to the 10 mg/kg monthly treatment arm.

BAN2401 demonstrated a dose-dependent reduction in amyloid plaques as measured by amyloid PET, and this reduction was statistically significant at all doses. At the highest dose of BAN2401 (10 mg/kg biweekly), an analysis of amyloid accumulated in the brain using standardized PET as measured on the Centiloid scale showed an observed mean at baseline of 74.5 and at 18 months of 5.5. Using a Mixed-effects Model with Repeated Measures (MMRM), the mean reduction in amyloid load was 70 units, which was statistically significant (p

Conventional statistical methods on predefined clinical endpoints at the 18 month final efficacy time point confirmed a dose-dependent slowing in cognitive decline from baseline on ADCOMS. The highest treatment dose of 10 mg/kg biweekly demonstrated a statistically significant slowing of clinical decline of 30% compared to placebo at 18 months (p=0.034). A statistically significant slowing of decline on ADCOMS was observed as early as 6 months (p

In a Bayesian analysis of ADCOMS at 12 months, the estimated probability that the highest dose of BAN2401 slows clinical decline more than placebo was 98%. While the criteria for early success at 12 months was pre-specified as an 80% or higher estimated probability of demonstrating a clinically significant difference (a 25% or greater slowing in clinical decline) from baseline compared to placebo, the actual probability for this criteria was 64% according to Bayesian analysis.

A dose-dependent increase in Aβ levels in cerebrospinal fluid (CSF) in patients on BAN2401 (highest dose at 18 months: p

BAN2401 demonstrated an acceptable tolerability profile through 18 months of study drug administration. The incidence rate of treatment-related adverse events was 26.5% for the placebo arm, 53.4% for the 10 mg/kg monthly treatment arm and 47.2% for the 10 mg/kg biweekly treatment arm. The most common treatment emergent adverse events were Amyloid Related Imaging Abnormalities (ARIA) and infusion-related reactions. Incidence of ARIA-E (edema) was 9.9% at the highest treatment dose, and not more than 10% in any of the treatment arms. Incidence of ARIA-E in APOE4 carriers was 14.6% at the highest dose. Per protocol, all patients presenting with ARIA-E on MRI were discontinued in the study. The incidence rate of serious adverse events was 17.6% for the placebo arm, 12.3% for the 10 mg/kg monthly treatment arm and 15.5% for the 10 mg/kg biweekly arm.

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval.

Biogen Safe Harbor Statement

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 about results from the Phase II study of BAN2401; the potential clinical effects of BAN2401; the potential benefits, safety, and efficacy of BAN2401 and therapies for other neurological diseases; the clinical development program for BAN2401; risks and uncertainties associated with drug development and commercialization; the timing and status of current and future regulatory filings; Biogen’s strategy and plans; the anticipated benefits and potential of Biogen’s collaboration arrangements with Eisai; and the potential of Biogen’s commercial business and pipeline programs, including BAN2401, elenbecestat, and aducanumab. These forward-looking statements may be accompanied by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “potential,” “possible,” “will,” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, unexpected concerns that may arise from additional data, analysis, or results obtained during clinical trials; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of Biogen’s drug candidates, including BAN2401, elenbecestat, and/or aducanumab; the occurrence of adverse safety events; risks of unexpected costs or delays; the risks of other unexpected hurdles; uncertainty of success in the development and potential commercialization of BAN2401, elenbecestat, and/or aducanumab, which may be impacted by, among other things, unexpected concerns that may arise from additional data or analysis, the occurrence of adverse safety events, failure to obtain regulatory approvals in certain jurisdictions, failure to protect and enforce Biogen’s data, intellectual property, and other proprietary rights and uncertainties relating to intellectual property claims and challenges; uncertainty as to whether the anticipated benefits and potential of Biogen’s collaboration arrangement with Eisai can be achieved; product liability claims; and third party collaboration risks. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogen’s expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in Biogen’s most recent annual or quarterly report and in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements are based on Biogen’s current beliefs and expectations and speak only as of the date of this press release. Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

About BAN2401

BAN2401 is a humanized monoclonal antibody for Alzheimer’s disease that is the result of a strategic research alliance between Eisai and BioArctic. BAN2401 selectively binds to neutralize and eliminate soluble, toxic Aβ aggregates that are thought to contribute to the neurodegenerative process in Alzheimer’s disease. As such, BAN2401 may have the potential to have an effect on disease pathology and to slow down the progression of the disease. Eisai obtained the global rights to study, develop, manufacture and market BAN2401 for the treatment of Alzheimer’s disease pursuant to an agreement concluded with BioArctic in December 2007. In March 2014, Eisai and Biogen entered into a joint development and commercialization agreement for BAN2401 and the parties amended that agreement in October 2017.

About Study 201

Study 201 is a placebo-controlled, double-blind, parallel-group, randomized Phase II clinical study in 856 patients with mild cognitive impairment (MCI) due to Alzheimer’s disease or mild Alzheimer’s dementia (collectively known as early Alzheimer’s disease) with confirmed amyloid pathology in the brain. This study used Bayesian Adaptive Randomization Design to automatically allocate newly enrolled patients into the study to treatment arms showing higher probability of efficacy based on the results of interim analyses. The study design included five dose regimens and placebo, and considered the efficacy of BAN2401 as an exploratory endpoint as well as dose responsiveness through 16 interim analyses that assessed potential for early success, an analysis based on ADCOMS at 12 months, and a comprehensive final analysis at 18 months. Patients who received treatment with BAN2401 were randomized to five dose regimens, 2.5 mg/kg biweekly (52 patients), 5 mg/kg monthly (51 patients), 5 mg/kg biweekly (92 patients), 10 mg/kg monthly (253 patients), or and 10 mg/kg biweekly (161 patients). Biomarker endpoints included changes in Aβ accumulated in the brain as measured by amyloid PET (positron emission tomography) as well as in cerebrospinal fluid (CSF), while ADCOMS (Alzheimer’s Disease Composite Score), Clinical Dementia Rating Sum of Boxes (CDR-SB) and Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) were measured as efficacy endpoints (clinical).

About ADCOMS

Developed by Eisai, ADCOMS (AD Composite Score) combines items from the ADAS-Cog (Alzheimer’s Disease Assessment Scale-cognitive subscale), CDR-SB (Clinical Dementia Rating Sum of Boxes) and the MMSE (Mini-Mental State Examination) scales to enable a sensitive detection of changes in clinical functions of early Alzheimer’s disease symptoms and changes in memory. This Study 201 utilizes ADCOMS as its key endpoint for assessing clinical symptoms.

About Amyloid PET Imaging

Amyloid PET (Positron Emission Tomography) imaging is a diagnostic method that enables the visualization of amyloid plaque present in the brain as well as the quantitative evaluation of amyloid plaque distribution and accumulation in the brain via administration of a minute amount of PET tracer, which specifically binds to amyloid plaque and marks it with positron. Amyloid PET imaging enables the assessment of pathology change and assistance of diagnosis of patients with Alzheimer’s-disease including MCI, and estimates the clinical effect of disease modifiers based on the amyloid hypothesis. SUVr (Standard Uptake Value Ratio) calculates the ratio of strength of accumulation of PET tracer in a region of interest in the brain to an area of the brain (reference region) which shows low and stable accumulation of PET tracer. These SUVr values can be used to quantitatively compare and evaluate the accumulation of amyloid. When integrating and assessing biomarkers of the change in Aβ accumulation measured by different tracers, it is necessary to compensate for the differences in measured values between the PET tracers. This has led to the development of a 100-point scale by the GAIIN Centiloid project, termed “Centiloid,” which is an average value of zero in “high certainty” amyloid negative subjects and an average of 100 in “typical” Alzheimer’s disease (AD) patients (Klunk et al., 2015). In this study, this Centiloid scale was used to standardize SUVr measurement values to evaluate the decrease in amyloid burden.

About the Joint Development Agreement between Eisai and Biogen for Alzheimer’s Disease

Eisai and Biogen are widely collaborating on the joint development and commercialization of Alzheimer’s disease treatments. Eisai serves as the lead in the co-development of elenbecestat, a BACE inhibitor, and BAN2401, an anti-amyloid beta (Aβ) protofibril antibody, while Biogen serves as the lead for co-development of aducanumab, Biogen’s investigational anti-amyloid beta (Aβ) antibody for patients with Alzheimer’s disease, and the companies plan to pursue marketing authorizations for the three compounds worldwide. If approved, the companies will also co-promote the products in major markets, such as the United States, the European Union and Japan.

As to BAN2401 and elenbecestat, both companies will equally split overall costs, including research and development expenses. Eisai will book all sales for elenbecestat and BAN2401 following marketing approval and launch, and profits will be equally shared between the companies.

About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides,” which we call our human health care (hhc) philosophy. With approximately 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to address unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.

Leveraging the experience gained from the development and marketing of Aricept®, a treatment for Alzheimer’s disease and dementia with Lewy bodies, Eisai has been working to establish a social environment that involves patients in each community in cooperation with various stakeholders including the government, healthcare professionals and care workers, and is estimated to have held over ten thousand dementia awareness events worldwide. As a pioneer in the field of dementia treatment, Eisai is striving to not only develop next generation treatments but also to develop diagnosis methods and provide solutions.

For more information about Eisai Co., Ltd., please visit www.eisai.com.

About Biogen

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissman, Heinz Schaller, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp, and today has the leading portfolio of medicines to treat multiple sclerosis; has introduced the first and only approved treatment for spinal muscular atrophy; and is focused on advancing neuroscience research programs in Alzheimer’s disease and dementia, neuroimmunology, movement disorders, neuromuscular disorders, pain, ophthalmology, neuropsychiatry, and acute neurology. Biogen also manufactures and commercializes biosimilars of advanced biologics.

Biogen routinely posts information that may be important to investors on its website at www.biogen.com. To learn more, please visit www.biogen.com and follow Biogen on social media – Twitter, LinkedIn, Facebook, Youtube.

About BioArctic AB

BioArctic AB (publ) is a Swedish research-based biopharma company focusing on disease modifying treatments and reliable biomarkers and diagnostics for neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. The company also develops a potential treatment for Complete Spinal Cord Injury. BioArctic focuses on innovative treatments in areas with high unmet medical needs. The company was founded in 2003 based on innovative research from Uppsala University, Sweden. Collaborations with universities are of great importance to the company together with our strategically important global partners in the Alzheimer (Eisai) and Parkinson (AbbVie) projects. The project portfolio is a combination of fully funded projects run in partnership with global pharmaceutical companies and innovative in-house projects with significant market- and out-licensing potential. BioArctic’s B-share is listed on Nasdaq Stockholm Mid Cap (STO:BIOA B). www.bioarctic.com.

Source: Biogen Inc.

Posted: July 2018

Tagged with:

About author

Related Articles