With a meaningful Alzheimer's disease treatment, the demand for Cogstate's test can be expected to accelerate above the minimum sales royalties in coming years (around US$2 million a year over the next three years). It will also strongly support continued interest in Alzheimer's disease drug development, which makes up around 70% of the company's core business.

Lecanemab will be commercialised by Eisai with Biogen to share in the profits. Eisai's share price is up 32% (up US$3.6 billion) since the data was released, Biogen's share price is up 35% (up US$10.1 billion), and Cogstate's share price jumped similarly by 49%.

There are quite a few differences with Aduhelm, the Alzheimer's disease drug therapy that was also developed by Biogen and Eisai but has been a commercial failure. Data for lecanemab has been consistently very good. In a Phase II study in 856 patients, cognitive decline was slowed by 47% and 30% using the ADAS-Cog and ADCOMS tests respectively.

Lecanemab Phase III Results
In the Phase III study, lecanemab achieved a statistically significant result on the primary endpoint (p=0.00005), using the CDR-CB test. Cognitive decline was slowed by 27% at 18 months over placebo. Across all time points after six months there was a statistically significant difference with the placebo group (p<0.01 at all time points).

What was also impressive is that all secondary endpoints were met with statistical significance (P<0.01 across all measures).

With respect to safety, lecanemab delivered a far improved profile over Aduhelm. The main issue with this class of drugs is that they can cause brain swelling (ARIA-E) with the antibody drugs binding to beta amyloid in the brain.

Aduhelm caused ARIA-E in 35% of patients compared to an incidence of just 12.5% with lecanemab. Symptomatic (that observed by patients) ARIA-E incidence was only 2.8% for lecanemab compared to 9.1% for Aduhelm.

ARIA-E usually resolves over time. In some cases ARIA-H occurs, which is small spots of bleeding in or on the surface of the brain. For lecanemab, the incidence was 17% compared to 8.7% in the placebo group although symptomatic ARIA-H was observed in just 0.7% of patients. ARIA-H occurred in around 22% of patients in the Aduhelm studies.

Another difference with lecanemab is that Eisai, not Biogen, is leading the commercialisation of this therapy.

Eisai's Development Plan
Eisai plans to file lecanemab for approval in the US, Japan and Europe by the end of March. The company has filed the drug for accelerated approval with the FDA, with a decision expected by January 6 next year (PDUFA date). However, it will also be filing for full approval based on this data.

Improved Delivery Studies
One of the constraints with lecanemab is that it needs to be infused every two weeks. Eisai has completed a bioequivalence study (in 60 healthy subjects) with lecanemab using a subcutaneous version that can be injected at home. It is also due to commence a bioequivalence study with a single use 'auto injector' for subcutaneous injection (in 160 healthy subjects).

Other Efficacy Studies
Eisai is conducting a 1,400 patient study in cognitively normal patients (over 55 years of age) with high brain amyloid levels. They will be treated for four years at half the dose trialled in the Phase III study with changes in cognition and tau levels being endpoints.

A two-year, open label, extension study in 250 patients from the Phase II study is continuing.

A 168-patient study in people with a genetic mutation for Alzheimer's disease started at the end of last year. The subjects are either cognitively normal or have early-stage disease. Patients will be followed over four years – with changes in tau levels the main endpoint and cognitive changes in symptomatic patients a secondary endpoint. All patients will receive lecanemab, with the active arm also receiving Eisai's tau binding antibody, E2814.

Summary
Eisai developed one of the first Alzheimer's disease drugs, Aricept, in the 1990s, launching the drug in over 100 countries. It has a firm commitment to this disease area.

The results from its Phase III study look likely to place lecanemab as the base building block for combination treatments for this disease.

Whilst some argue the cognitive benefit is moderate (a 27% slowing in cognitive decline), the compounded effect over five years is likely to be substantially greater, and some patients will benefit more than others, depending on their disease etiology and their stage of disease at time of treatment.

Combining lecanamab with a tau inhibitor will be of significant interest, as will be treating patients with high amyloid levels before cognitive decline has been detected and longer-term therapy.

Eisai has firmly wedged open the Alzheimer's disease treatment door, from which point cumulative improvements in treatment outcomes can now be expected. After two decades of late-stage trial disappointments, optimism with this disease area has finally emerged. For Cogstate, it's a very good time to be a technology service company for Alzheimer's disease R&D.

Cogstate is capitalised at $362 million.

Bioshares recommendation: Buy

 

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