Additional Detailed Analyses From Phase 2 Study 201 of Lecanemab Published as Three Papers in Peer-Reviewed Journals
TOKYO and CAMBRIDGE, Mass., March 30, 2023 (GLOBE NEWSWIRE) -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that three additional detailed analyses from the Phase IIb clinical study (Study 201), evaluating the efficacy and safety of lecanemab for mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD), were published in the peer-reviewed journals.
Study 201 was a multicenter, double-blind, placebo-controlled, Phase 2b trial conducted in 856 patients with early AD. Its core study evaluated key efficacy assessments, including clinical change on the AD Composite Score (ADCOMS) as the primary endpoint at 12 months and as key secondary endpoints, ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) and AD Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) at 18 months. Following analysis of the 18-month core phase, an intervening off-treatment period (gap period) ranging from 9-59 months (mean 24 months) was taken, which was followed by an OLE with 10 mg/kg IV bi-weekly lecanemab dosing to assess long-term safety and tolerability. The results of the primary analysis in the core study including clinical efficacy and biomarkers have already been published, showing a consistent reduction in clinical decline across several clinical and biomarker endpoints with lecanemab 10 mg/kg bi-weekly dosing.
1. Detailed results on biomarker, cognitive, and clinical effects from Study 201.
In the OLE, lecanemab 10 mg/kg biweekly treatment showed a decrease in brain amyloid beta (Aß) accumulation measured by amyloid PET, a decrease in the plasma Aß42/40 ratio, and a decrease in plasma p-tau181.
The potential for disease modification with lecanemab is supported by an increasing difference in clinical measures between the lecanemab group and placebo group in line with time during the core period, differences in clinical progression between subjects who received 10 mg/kg lecanemab and those who received placebo in the core period, which remained persistent throughout the gap period, and an impact on biological measures that reflect key pathophysiological changes in AD. Furthermore, the results showed the potential for monitoring the treatment effects of lecanemab using plasma biomarkers.
2. Consistency of efficacy results across various clinical measures and statistical methods in Study 201.
3. ARIA profile in Study 201
Overall ARIA-E events in the OLE phase were generally consistent with the rate seen in the lecanemab 10 mg/kg biweekly group in the core study (four subjects treated with placebo in the core study had ARIA-E in the OLE (4 of 45: 8.9%). As with the core study, most ARIA-E occurred within 3 months after receiving the initial dose in the OLE and had mostly mild to moderate in radiographic severity. ARIA-H events in the OLE were generally consistent with the rate seen in the lecanemab 10 mg/kg biweekly group in the core study. ARIA-H events were mostly mild or moderate in severity. One symptomatic case of ARIA-H, intracerebral hemorrhage > 1cm, was reported in OLE. This subject did not have concurrent ARIA-E, and the adverse event resolved with residual visual field defect.
PK/PD modeling showed that the incidence of ARIA-E was correlated with Cmax at steady state. Based on the fact that lecanemab was generally well tolerated at the highest dose in this study, the Phase 3 Clarity AD study was conducted without dose titration. A subcutaneous formulatin that may potentially reduce the Cmax of lecanemab is being developed and evaluated to determine if there is a reduction of the incidence of ARIA-E compared to intravenous formulation.
Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
To learn more, visit www.LEQEMBI.com.
1. About Lecanemab
Please see full Prescribing Information in the United States.
Lecanemab-irmb was approved under the accelerated approval pathway in the U.S. and was launched in the U.S. on January 18, 2023. The accelerated approval was based on Phase 2 data that demonstrated that lecanemab reduced the accumulation of Aß plaque in the brain, a defining feature of AD, and its continued approval may be contingent upon verification of lecanemab’s clinical benefit in a confirmatory trial. The FDA determined that the results of the Phase 3 Clarity AD study can serve as the confirmatory study to verify the clinical benefit of lecanemab. In November 2022, the results of Clarity AD study were presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference and simultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway on January 6, 2023. On March 3, 2023, the FDA accepted Eisai’s sBLA based on the Clarity AD clinical data, and the lecanemab application has been granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of July 6, 2023. The FDA is currently planning to hold an Advisory Committee to discuss this application but has not yet publicly announced the date of the meeting. Eisai submitted an application for manufacturing and marketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. The Priority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, which was accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was granted on February 27, 2023 .
Eisai has completed a lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD OLE.
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, has been ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S., funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.
Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, has been ongoing.
2. About the Collaboration between Eisai and Biogen for AD
3. About the Collaboration between Eisai and BioArctic for AD
4. About Eisai Co., Ltd.
In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on Twitter @Eisai_SDGs.
5. About Biogen
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.
Biogen Safe Harbor
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 and AHEAD 3-45 study; 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 lecanemab; actual timing and content of submissions to and decisions made by the regulatory authorities regarding lecanemab; uncertainty of success in the development and potential commercialization of lecanemab; 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 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 news 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.