New Body Blow For Aducanumab As Japan Asks For More Data
Executive Summary
Request for additional data after a surprise review committee meeting sets back approval in potentially large market, adding to Biogen and Eisai’s woes following the recent EU negative opinion and poor performance and price cut in the US.
Japan has decided not to approve Eisai Co., Ltd. and Biogen, Inc.’s Alzheimer’s drug aducanumab, at least for the time being, until the co-developers can provide additional clinical data to satisfy regulators of the amyloid-targeting antibody’s efficacy.
The decision effectively marked a stumble at the first hurdle for the controversial therapy, which was considered at an extraordinary meeting of a review committee of the Ministry of Health, Labour and Welfare’s Pharmaceutical Affairs and Food Sanitation Council on 22 December.
It is rare for the panel to call such unscheduled meetings on a single product and the move and negative decision caught many analysts by surprise, given that most drugs it considers usually go on to approval.
In aducanumab’s case, however, Biogen and Eisai announced after the meeting (where discussions are not publicly disclosed) that regulators had “decided to continue deliberations” on the approval submission, which was made in December 2020 and granted a standard review.
The committee “is seeking additional data” as part of this process and discussions with Japan’s drug regulatory authority, the Pharmaceutical and Medical Devices Agency, would continue to establish and agree the additional data requirements, the firms said.
While the nature of these was not immediately elucidated, if reviewers are unconvinced by the existing clinical data for aducanumab and are looking for further clinical trials, this could set back any Japanese approval by years.
The companies stressed in the meantime that they “remain committed to bringing aducanumab to patients in Japan expeditiously.”
Potentially Large Market
Commercially, the decision also represents a major blow to the two firms, on top of the so far poor sales performance of the drug in the US, where it was controversially approved as Aduhelm in June. The impact of the decision was reflected in the 8.4% plunge in Eisai’s share price in morning trading in Tokyo on 23 December.
The number of Alzheimer’s patients in Japan is rising along with a rapidly ageing society, with around 60% of the country’s estimated six million dementia patients having the disorder, presenting a large potential patient population.
Eisai, which as a long history with the now genericized Alzheimer’s drug Aricept (donepezil), has pointed in the past to data putting the total direct and social costs of the disease in the country as Japan as JPY12,628bn ($110.6bn). Despite the obvious need however, regulators will still need to be convinced of the clinical utility of any new treatment.
Analysts had been forecasting substantial sales for aducanumab in Japan following any approval, with Citi for instance projecting a peak annual figure of JPY60bn ($526m) at reimbursement prices and Jefferies $878m in the fiscal year ending March 2030.
Multiple analysts in Japan had been positive on approval prospects before the meeting, albeit with potential strict use and monitoring requirements and prediction of a relatively low reimbursement price under Japan’s national health insurance system.
In the US, Biogen has just halved the drug’s list price to $28,200 and is also preparing to slash corporate costs by $500m given the low uptake of Aduhelm, which generated just $300,000 in the third quarter.
EU Negative Opinion, Other Plans
The new Japanese setback comes shortly after authorities in the EU rejected the drug over concerns around clinical efficacy and potential side effects.
Biogen is seeking a re-examination of the negative opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency in its submission for approval for use in mild cognitive impairment and dementia associated with early Alzheimer’s.
Aducanumab’s only other approval globally so far is in the United Arab Emirates.
The antibody, which targets the brain amyloid beta plaques characteristic of Alzheimer’s, was contentiously granted accelerated approved in the US based on limited data and observed reductions in amyloid beta plaques as a biomarker. (Also see "Biogen/Eisai Win On Aduhelm Approval Bet And Wager Next On Price" - Scrip, 7 Jun, 2021.)
A Phase IV confirmatory study in the US, to be conducted as part of the regulatory process there, is now set to start next May with results due in 2026. (Also see "Biogen Pledges Aduhelm Confirmatory Data By 2026, Renewing Spotlight On FDA’s Lengthy Original Plan" - Pink Sheet, 16 Dec, 2021.)
In Japan, Eisai does have a back-up in the Alzheimer’s sector in the form of lecanemab (BAN2401), an amyloid beta protofibril-targeting antibody now progressing through domestic Phase III trials for mild cognitive impairment/early disease and asymptomatic Alzheimer’s.
A rolling submission for the candidate in the US was initiated by Eisai in September for the treatment of early disease under an accelerated approval pathway; lecanemab also has US breakthrough therapy designation.