Subcutaneous Formulation Interim Data; Safety And Effects On Brain Amyloid
Weekly subcutaneous (SC) administration showed 14% greater amyloid plaque removal than biweekly IV administration as suggested in a preliminary analysis using amyloid PET at 6 months of treatment.
The SC substudy, evaluating the SC formulation in an open-label extension (OLE) of the Clarity AD study, included 72 patients who received LEQEMBI for the first time as the SC formulation, and 322 patients who received intravenous (IV) LEQEMBI in the Clarity AD core study followed by SC administration in this substudy. Reduction from baseline of amyloid in the brain by amyloid PET at 6 months in the newly treated SC patients by centiloid reduction was -40.3 +/- 2.27 in SC administration compared to -35.4 +/- 1.14 in IV administration.1
SC Pharmacokinetics (AUC) Higher Than IV By 11%
Weekly SC administration AUC are 11% higher than the biweekly IV formulation. 90% CI for drug exposure for SC vs. IV is within the bioequivalence limits of 80 to 125%. These data could allow
Lower Systemic Injection Reaction Rates With SC As Compared To IV
Systemic injection/infusion reactions are uncommon and mild with SC administration, and in particular have not been observed in patients who received LEQEMBI for the first time as the SC formulation. There was a low rate of local injection site reactions (8.1%) in SC treated patients overall. Most were mild and moderate in severity consisting of redness, irritation, or swelling. No skin rash or other hypersensitivity reactions were reported.1
ARIA Rates Of IV Formulation In Clarity AD Core Study Consistent With Rates In First-Time LEQEMBI Patients Entering The SC Substudy In Clarity AD OLE
The incidence of ARIA-E with SC was similar to the IV. The incidences of ARIA-E, ARIA-H (cerebral microhemorrhage due to ARIA, cerebral hemorrhage, and brain surface hemosiderin deposition) and ARIA-H alone (ARIA-H without ARIA-E) with IV in the Clarity AD core study (n=898) were 12.6%, 17.3% and 8.9%, respectively. In newly treated patients in the SC substudy of the Clarity AD OLE (n=72), the incidences of ARIA-E, ARIA-H and ARIA-H alone were 16.7%, 22.2% and 8.3%, respectively. However, due to the sample size of newly treated patients in the SC substudy, no exact comparison can be made.1
Based on Phase II and III clinical studies, Cmax (maximum exposure) was the strongest predictor of ARIA-E incidence following IV administration. In the SC substudy, the steady-state exposure (AUCss) appears to be a better predictor of ARIA-E rates in the SC due to a relatively stable exposure profile. 1
Latest Data From Tau Pet Longitudinal Substudy, Including A Post-Hoc Analysis Of The Low And Intermediate + High-Tau Subpopulations In The Clarity AD 18 Month Core Study
76% of patients showed no decline and 60% showed clinical improvement at 18 months in low-tau / earlier stage early AD population.
The Clarity AD study included an optional Tau PET substudy and used the tau PET probe MK6240 to identify patients with a low accumulation of tau in the brain, which represents the earlier stage of early AD.
The low-tau subpopulation, which is in the earlier stages of early AD, is thought to show slow disease progression. In the low-tau subpopulation, 76% of the LEQEMBI group showed no deterioration and 60% showed clinical improvement after 18 months of treatment in the primary endpoint, Clinical Dementia Rating - Sum of Boxes (CDR-SB), compared with 55% and 28% of the placebo group, respectively.1
Importantly, in this low-tau subgroup, LEQEMBI treatment also showed consistent clinical response across multiple endpoints. In this population, LEQEMBI treatment favored cognition and function in the earlier stage of early AD.1
The efficacy results of the Tau PET substudy in the Clarity AD study, which observed tau pathology in the brain by tau PET, were consistent with overall results of the Clarity AD study.1
Tau PET Substudy Showed LEQEMBI Slows Development Of Tau Tangles In Early AD; Tau Spread In The Brain Is A Hallmark Of Disease Progression.
In the Clarity AD Tau PET substudy, LEQEMBI treatment slowed the buildup of tau proteins in the temporal lobe (early Braak region), where tau accumulation was observed in the earlier stage of early AD. In the Tau PET substudy, LEQEMBI suppressed the accumulation of tau in the medial temporal brain region in low-tau subpopulations, and in a broader range of brain regions in the intermediate and higher accumulation groups. This suggests that LEQEMBI treatment may have different effects on brain regions indexed by tau depending on the stage of the disease.1 The spread of tau in the brain is a hallmark of AD progression.2
Efficacy Results From LEQEMBI Clarity AD Open-Label Extension Study
LEQEMBI Patients Continued to Show Benefit at 24 Months of Treatment
In the 18-month core study of Clarity AD, there was a statistically significant difference in global cognition and function as measured by CDR-SB between the LEQEMBI and placebo groups. The separation in CDR-SB between the group that continued to receive LEQEMBI (early start group) and the group who switched from placebo to LEQEMBI (delayed start group) was maintained during the 6-month OLE following the core study. This indicates that similar disease trajectory for both early and delayed start groups occurred with LEQEMBI administration.1
The blood biomarker results (plasma A42/40 ratio, ptau181, GFAP and NfL) showed improvement even after delayed initiation of treatment with LEQEMBI.1 These results suggest that LEQEMBI treatment may affect clinical outcomes through improvement of AD pathology.1
The Mechanism-Based Rationale Of LEQEMBI Treatment In Early AD
Dual-Acting LEQEMBI3 Continues To Support Brain Neuron Function3,4,5 By Removing Highly Toxic Proteins (Protofibrils)2,4 That Can Cause Neuronal Injury And Death Even After Plaque Removal,5-8 Offering Patients The Opportunity For Continued Benefit.
LEQEMBI has a unique dual action1,3 that binds more selectively to highly toxic protein (protofibrils) in addition to rapidly clearing plaque,7 and continues to support neuronal function3,4 by removing protofibrils that can cause neuronal injury and death after plaque has been cleared.5-8
This release discusses investigational uses of agents in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational agents will successfully complete clinical development or gain health authority approval.
Phase III Clarity AD study is a placebo-controlled, double-blind, parallel-group, randomized study to evaluate the efficacy and safety of LEQEMBI 10 mg/kg bi-weekly for 18 months in 1,795 people living with early AD (core study). An OLE is being conducted after the core study. SC dosing is currently being evaluated in the Clarity AD OLE.
Using the MK6240 tau PET probe, tau accumulation in the brain was defined as low tau accumulation group (MK6240 cutoff value 2.91, 10 subjects).
Multiple endpoints: CDR-SB, a numeric scale used to quantify the severity of symptoms of dementia; ADAS-Cog14, common cognitive assessment instrument used in AD clinical trials all over the world and ADCS MCI-ADL, a scale to assess the parties' activities of daily living.
Contact:
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Tel: 1-201-753-1945
Email: LibbyHolman@eisai.com
About Lecanemab
Lecanemab is the result of a strategic research alliance between
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About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments to address a defining pathology of Alzheimer's disease. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.
Biogen Safe Harbor
This news release contains forward-looking statements about the potential clinical effects of LEQEMBI; the potential benefits, safety and efficacy of LEQEMBI; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Alzheimer's disease; the anticipated benefits and potential of Biogen's collaboration arrangements with
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 studies, including the Clarity AD clinical trial, AHEAD 3-45 study and SC substudy; the occurrence of adverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles; regulatory submissions may take longer or be more difficult to complete than expected; 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 LEQEMBI; actual timing and content of submissions to and decisions made by the regulatory authorities regarding LEQEMBI; uncertainty of success in the development and potential commercialization of LEQEMBI; failure to protect and enforce Biogen's data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; third party collaboration risks and the direct and indirect impacts of the ongoing COVID-19 pandemic on Biogen's business, results of operations and financial condition. 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
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