Eisai says sub-Q Leqembi holds up against current infused version

2023-10-25

临床结果上市批准临床3期

Eisai on Wednesday reported that a weekly subcutaneous version of Leqembi (lecanemab) held its own against the currently approved infused form of the Alzheimer's disease drug when it comes to amyloid plaque removal. However, rates of serious side effects with the experimental new formulation were higher, according to an analysis presented by the Japanese drugmaker at the Clinical Trials on Alzheimer's Disease (CTAD) conference.

The original intravenous form of the anti-amyloid antibody was granted a full approval by the FDA in July based on Phase III Clarity AD study results showing that it slowed cognitive decline by 27% in people with early Alzheimer's. Eisai, which is partnered on the drug with Biogen, said its latest analysis compared data from 72 newly-treated patients with early Alzheimer's disease who were given Leqembi by subcutaneous injection to data from 322 patients who had received the drug by infusion in Clarity AD, followed by subcutaneous administration in this substudy.

A weekly shot formulation of Leqembi, given as two consecutive injections, could potentially simplify its use and allow the treatment to be taken at home, as opposed to requiring patients to travel to an infusion centre twice a month.

After six months of treatment, the subcutaneous form of Leqembi removed 14% more amyloid than the approved intravenous version, according to results presented at CTAD. The decrease from baseline in brain amyloid was measured to be -40.3 centiloids for the subcutaneous group, compared to -35.4 with intravenous administration. Blood concentration levels of the drug were also 11% higher with subcutaneous Leqembi than the currently-marketed version, Eisai said.

More serious side effects

Regarding safety, Eisai said rates of infusion- or injection-related side effects were lower for the subcutaneous formulation, but serious side effects typically occurred more often. The incidence of amyloid-related imaging abnormalities (ARIA) with oedema (ARIA-E) was 16.7% for the subcutaneous group, versus 12.6% for intravenous patients in the Clarity AD study. Meanwhile, ARIA-E along with ARIA characterised by cerebral microhaemorrhages (ARIA-H) occurred in 22.2% of the subcutaneous patients versus 17.3% of the intravenous group. Rates of ARIA-H alone were 8.3% and 8.9% for the two groups, respectively.

Still, Priya Singhal, Biogen's head of development, remarked "we believe that the safety is actually consistent." Referring to the 72-patient group, Singhal noted that "because it's a very small cohort…one or two cases can actually swing the numbers pretty significantly." Eisai and U Biogen said they plan to seek US approval of subcutaneous Leqembi by the end of March next year, based on data from 394 patients.

Tau substudy

Meanwhile, Eisai also presented findings from a Clarity AD substudy that used a tau positron emission tomography (PET) probe to identify patients with a low accumulation of tau in the brain, indicating they are in the earlier stage of early Alzheimer's.

According to the Japanese drugmaker, the post-hoc analysis found that 60% of patients at the very early stages of the disease showed a clinical improvement after taking the currently marketed version of Leqembi for 18 months based on the primary endpoint of Clinical Dementia Rating - Sum of Boxes (CDR-SB), compared to 28% for placebo. In addition, 76% of participants showed no decline in their condition, versus 55% in the placebo group.

Alex Scott, executive vice president of Eisai, said the company wanted to identify the earliest possible stage that patients could benefit from the drug. "We think this adds a dose of urgency to the system to identify these patients and treat these patients. It is sort of like with cancer, do you want to find cancer at stage three, or do you want us to find cancer in stage one or earlier?" Scott said.

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