Biogen, Eisai double down on Alzheimer's with lecanemab filing

Biogen and Eisai's first Alzheimer's disease drug Aduhelm is facing an uphill battle in the US market, but the partners are forging ahead with their second candidate lecanemab, starting a rolling submission to the FDA.

Like Aduhelm (aducanumab) lecanemab – also known as BAN2401 – is another amyloid-directed antibody but has a slightly different mechanism, targeting soluble amyloid beta protofibrils which haven't yet aggregated together to form the characteristic plaques in Alzheimer's brains.

The rolling submission follows an FDA breakthrough designation for lecanemab awarded in June on the back of a phase 2b trial – Study 201 – in 856 patients with mild cognitive impairment (MCI) due to Alzheimer's and amyloid pathology.

The placebo-controlled study showed a reduction of clinical decline across several clinical and biomarker endpoints at the highest doses of the antibody, according to Biogen and Eisai.

The trial measured 12-month change from baseline in the ADCOMS composite of cognitive tests, and while it missed the mark at that timepoint, reported in 2017, subsequent follow-up showed that a twice-monthly 10 mg/kg dose slowed progression on the ADCOMS and reduced brain amyloid accumulation.

Eisai and Biogen are also running a phase 3 trial of lecanemab called CLARITY AD in early symptomatic Alzheimer's, which has completed enrolment and is due to read out in 2024, as well as the late-stage AHEAD 3-45 trial in patients without symptoms but with elevated levels of amyloid.

The filing comes as Aduhelm continues to struggle to make headway since its controversial accelerated approval earlier this year that went against the advice of the FDA's own expert committee.

Take-up has been slower than expected, with a number of clinics refusing to administer Aduhelm and one even going so far as to ban Biogen reps from its premises, while some insurers have refused to cover the $56,000-per-year drug.

The antibody made second-quarter sales of $1.6 million in the first few weeks after its US launch, around half the amount expected.

The accelerated approval has inspired other companies developing amyloid-targeting drugs to press ahead with plans to file with the FDA.

Eli Lilly for example has said it will seek accelerated FDA approval of its candidate donanemab later this year, based on the results of the phase 2 TRAILBLAZER-ALZ study. Donanemab also has FDA breakthrough status.