Eisai, Biogen say Study 201 results of BAN2401 in early Alzheimer's disease not skewed; rather treatment effect related to drug

Eisai and Biogen presented sub-group analyses on Thursday from a mid-stage trial of BAN2401 at the Clinical Trials on Alzheimer's Disease (CTAD) conference suggesting that a previously reported treatment effect seen for the highest dose was related to the drug, and not to an imbalance of patients in the treatment groups. Results from Study 201 presented in July demonstrated that patients with early Alzheimer's disease given the highest dose of the experimental anti-amyloid beta protofibril antibody experienced 30-percent less cognitive decline versus placebo.

However, questions were raised as to whether the findings might have been skewed by a decision by European regulators to restrict enrollment of patients with the ApoE4 mutation from the group that received the highest BAN2401 dose of 10 mg/kg bi-weekly, potentially lowering the bar for success in this group. 

Biogen and Eisai disclosed in December 2017 that an independent data monitoring committee concluded that BAN2401 "did not meet the criteria for success" based on an interim analysis for the primary endpoint at 12 months. However, the final analysis found that at 18 months, the highest dose of the therapy did meet the main goal of significantly slowing clinical decline versus placebo and reducing amyloid beta in the brains of patients with early Alzheimer's disease. The drugmakers have since announced plans to initiate Phase III studies of the treatment. 

In the updated analysis released Thursday, results illustrated that at the highest BAN2401 dose, APOE4 carriers saw 63-percent less decline in disease progression at 18 months versus placebo, while non-carriers saw 7-percent less decline, as measured using Eisai's in-house developed Alzheimer's disease Composite Score (ADCOMS). "These results suggest that the treatment effect for the 10 mg/kg bi-weekly dose is related to treatment with BAN2401 and not due to an imbalance in subject allocation by ApoE4 status," Eisai and Biogen said. Additionally, a pooled analysis of the 10 mg/kg bi-weekly and 10 mg/kg monthly doses of BAN2401 showed 21-percent less decline in all patients based on the ADCOMS measure versus placebo at 18 months, with cognitive decline reduced by 25 percent and by 6 percent, respectively, for ApoE4 carriers and non-carriers.

Eisai and Biogen said they are discussing next steps for the BAN2401 development programme with regulatory agencies. The companies added that an open-label extension of patients in Study 201 is being planned, with enrolment expected to begin this year. 

Commenting on the news, Leerink Partners analyst Geoff Porges described the results as "thin" and "unconvincing." He remarked "in our view [these] data [are] confusing, suggesting only limited value for BAN2401 in the [ApoE4] carrier population, while the small number of patients remaining on drug at the 18-month time point and lack of clear dose responses diminish the reliability of this dataset." 

Baird analyst Brian Skorney agreed that the findings represent "really flawed clinical data." Meanwhile, Stifel analyst Paul Matteis noted "the small sample size limits our conviction in drawing any sort of firm conclusion," adding that "the irony however is that clinical data in [the larger sample of] APOE4 non-carriers look underwhelming…raising new unanswerable questions." 

Biogen and Eisai are jointly developing BAN2401 under the terms of a partnership forged in 2014. Eisai initially acquired global rights to the drug from BioArctic in 2007. 

For related analysis, see ViewPoints: Biogen, Eisai flip the script with BAN2401 raising new queries.

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