TOKYO, Nov 11, 2021 - (JCN Newswire) - Eisai Co., Ltd. and Biogen Inc. announced today results of new clinical, biomarker and safety assessments of brain amyloid reduction and five-year clinical status of people living with early Alzheimer's disease (AD) from the lecanemab Phase 2b 201 and the open-label extension (OLE) studies. The findings were presented and discussed in a late-breaking roundtable session with esteemed clinical researchers at the 2021 Clinical Trials on Alzheimer's Disease (CTAD) conference, November 9-12, 2021, in Boston, Massachusetts and virtually. Eisai recently initiated a rolling submission of a Biologics License Application (BLA) for lecanemab, an investigational anti-amyloid beta (Aβ) protofibril antibody, for the treatment of early AD, to the U.S. Food and Drug Administration (FDA) under the accelerated approval pathway.
OLE Study Explores Biomarkers and Clinical Effects Across Five Years
An OLE with 10 mg/kg IV biweekly lecanemab dosing was implemented after analysis of the 18-month, core phase (Study 201, Alz Res Therapy 13;21) with an intervening off-treatment period (gap period) ranging from 9-59 months (mean 24 months). The OLE phase evaluated the effect of lecanemab on amyloid PET over 12 months of treatment, including earlier time points (3 and 6 months) than in the core phase (12 and 18 months). This study design provided the opportunity to explore the biomarker and clinical effects of stopping and restarting lecanemab across five years of disease trajectory.
Amyloid Reduction Correlates with Clinical Benefit
The updated assessment of the OLE phase showed that treatment with lecanemab resulted in reduction of brain amyloid levels in as early as 3 months based on OLE data and robust clearance of amyloid plaque with more than 80% of participants (10/12) achieving amyloid negative status by 12-18 months of treatment as measured by PET (visual read). These results are consistent with core phase results. The 201 study core data suggested that clinical efficacy (ADCOMS) is correlated with amyloid reduction (PET SUVr) at both the population (correlation coefficients=0.832, p-value=0.080) and subject levels (correlation coefficients=0.201, slope=0.199, p=0.036). Amyloid PET levels were significantly reduced by quantitative assessment in newly treated OLE subjects in as early as 3 months after initiation of treatment. Additionally, the core data suggested that clinical efficacy is correlated with plasma Aβ at both the population (correlation coefficients=-0.306, not significant) and subject levels (correlation coefficients=-0.208, slope=-3.957, p- value=0.050).
Potential Slowing of Cognitive Decline May Suggest Disease-Modifying Effect
The clinical treatment difference in study participants between lecanemab treatment and placebo at the end of core period is maintained after discontinued dosing over the 24-month Gap period. The reduction of clinical decline of participants receiving the highest dose of lecanemab relative to placebo at the end of the 18-month, core period showed a difference of 0.05 in ADCOMS (placebo 0.19, lecanemab 0.14). This treatment difference of 0.10 in subjects who entered OLE was maintained while off-treatment during the gap period up to the beginning of the OLE (placebo 0.28, lecanemab 0.18). Similar findings were observed for CDR-SB and ADAS-Cog, although both groups continued to progress. This pattern of sustained treatment effect after stopping lecanemab, reflected in biomarkers as well amyloid PET, plasma Aβ42/40 and ptau181 is consistent with a disease-modifying effect.
Blood Tests May be Able to Monitor Lecanemab Treatment Effects
New results were presented for two new blood tests that were measured in the Phase 2b and OLE studies: Plasma Aβ42/40 ratio and Plasma p-tau181. Plasma Aβ42/40 ratio changes suggested an inverse correlation with amyloid PET changes. Both amyloid PET and blood Aβ show correlation with ADCOMS at the population and individual levels in the core phase (PET correlation coefficients=0.832 population, 0.201 subject level and Aβ plasma correlations coefficients:-0.306 population, -0.208 subject level). Monitoring of treatment effects using plasma biomarkers may allow simple dose modification following robust amyloid removal (e.g., less frequent and/or lower dose).
Safety Profile with Low Incidence of ARIA-E and Symptomatic ARIA Rate in Core and OLE
Consistent with the safety findings in the core period, lecanemab was well-tolerated with <10% incidence of ARIA-E at 10 mg/kg biweekly in the Core and OLE. The incidence of symptomatic ARIA-E was <2% in Core and OLE. This safety profile enables lecanemab to be initiated at the therapeutic dose without titration.
"The latest lecanemab findings provide greater insight into the time course and extent of amyloid reduction observed with lecanemab, and the relationship to clinical outcomes and blood-based biomarkers," said Lynn Kramer, M.D., Chief Clinical Officer, Neurology Business Group, Eisai. "The Clarity AD Phase 3 Study in Early AD, which completed enrollment of 1795 subjects in March, aims to verify these findings."
The presentation video and slides will be available on the investors' section of the Eisai Co., Ltd. Website by 10:00 p.m. U.S. EST on November 11.
This release discusses the investigational use of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.
For more information, visit https://www.eisai.com/news/2021/pdf/enews202185pdf.pdf.
Source: Eisai
Copyright 2021 JCN Newswire . All rights reserved.
OLE Study Explores Biomarkers and Clinical Effects Across Five Years
An OLE with 10 mg/kg IV biweekly lecanemab dosing was implemented after analysis of the 18-month, core phase (Study 201, Alz Res Therapy 13;21) with an intervening off-treatment period (gap period) ranging from 9-59 months (mean 24 months). The OLE phase evaluated the effect of lecanemab on amyloid PET over 12 months of treatment, including earlier time points (3 and 6 months) than in the core phase (12 and 18 months). This study design provided the opportunity to explore the biomarker and clinical effects of stopping and restarting lecanemab across five years of disease trajectory.
Amyloid Reduction Correlates with Clinical Benefit
The updated assessment of the OLE phase showed that treatment with lecanemab resulted in reduction of brain amyloid levels in as early as 3 months based on OLE data and robust clearance of amyloid plaque with more than 80% of participants (10/12) achieving amyloid negative status by 12-18 months of treatment as measured by PET (visual read). These results are consistent with core phase results. The 201 study core data suggested that clinical efficacy (ADCOMS) is correlated with amyloid reduction (PET SUVr) at both the population (correlation coefficients=0.832, p-value=0.080) and subject levels (correlation coefficients=0.201, slope=0.199, p=0.036). Amyloid PET levels were significantly reduced by quantitative assessment in newly treated OLE subjects in as early as 3 months after initiation of treatment. Additionally, the core data suggested that clinical efficacy is correlated with plasma Aβ at both the population (correlation coefficients=-0.306, not significant) and subject levels (correlation coefficients=-0.208, slope=-3.957, p- value=0.050).
Potential Slowing of Cognitive Decline May Suggest Disease-Modifying Effect
The clinical treatment difference in study participants between lecanemab treatment and placebo at the end of core period is maintained after discontinued dosing over the 24-month Gap period. The reduction of clinical decline of participants receiving the highest dose of lecanemab relative to placebo at the end of the 18-month, core period showed a difference of 0.05 in ADCOMS (placebo 0.19, lecanemab 0.14). This treatment difference of 0.10 in subjects who entered OLE was maintained while off-treatment during the gap period up to the beginning of the OLE (placebo 0.28, lecanemab 0.18). Similar findings were observed for CDR-SB and ADAS-Cog, although both groups continued to progress. This pattern of sustained treatment effect after stopping lecanemab, reflected in biomarkers as well amyloid PET, plasma Aβ42/40 and ptau181 is consistent with a disease-modifying effect.
Blood Tests May be Able to Monitor Lecanemab Treatment Effects
New results were presented for two new blood tests that were measured in the Phase 2b and OLE studies: Plasma Aβ42/40 ratio and Plasma p-tau181. Plasma Aβ42/40 ratio changes suggested an inverse correlation with amyloid PET changes. Both amyloid PET and blood Aβ show correlation with ADCOMS at the population and individual levels in the core phase (PET correlation coefficients=0.832 population, 0.201 subject level and Aβ plasma correlations coefficients:-0.306 population, -0.208 subject level). Monitoring of treatment effects using plasma biomarkers may allow simple dose modification following robust amyloid removal (e.g., less frequent and/or lower dose).
Safety Profile with Low Incidence of ARIA-E and Symptomatic ARIA Rate in Core and OLE
Consistent with the safety findings in the core period, lecanemab was well-tolerated with <10% incidence of ARIA-E at 10 mg/kg biweekly in the Core and OLE. The incidence of symptomatic ARIA-E was <2% in Core and OLE. This safety profile enables lecanemab to be initiated at the therapeutic dose without titration.
"The latest lecanemab findings provide greater insight into the time course and extent of amyloid reduction observed with lecanemab, and the relationship to clinical outcomes and blood-based biomarkers," said Lynn Kramer, M.D., Chief Clinical Officer, Neurology Business Group, Eisai. "The Clarity AD Phase 3 Study in Early AD, which completed enrollment of 1795 subjects in March, aims to verify these findings."
The presentation video and slides will be available on the investors' section of the Eisai Co., Ltd. Website by 10:00 p.m. U.S. EST on November 11.
This release discusses the investigational use of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.
For more information, visit https://www.eisai.com/news/2021/pdf/enews202185pdf.pdf.
Source: Eisai
Copyright 2021 JCN Newswire . All rights reserved.
