Leqembi maintenance dose filed in US, but SC form delayed

Eisai has filed to extend the label for its Alzheimer’s disease therapy Leqembi to include a maintenance dosing regimen that would reduce the number of intravenous infusions needed to one per month.

The move is just part of the drugmaker’s original plan, however, which was to also submit a marketing application for a once-weekly, subcutaneous formulation of Leqembi (lecanemab), according to Eisai and Biogen, its partner for the drug. That has now been held up for procedural reasons.

Leqembi is currently approved by the FDA as a therapy to clear amyloid plaques from the brains of Alzheimer’s patients with mild cognitive impairment or mild dementia using twice-monthly infusions, but there have been questions about whether there is a continued benefit from staying on treatment in a maintenance phase.

The new marketing application would allow a step-down in dosing frequency for patients who complete an initial induction phase of treatment with Leqembi, the duration of which remains under discussion with the FDA.

Following a request for immunogenicity data, Eisai had planned to file a rolling application for the subcutaneous formulation last month under the existing fast-track and breakthrough therapy designations for intravenous Leqembi. However, that has been scuppered by the FDA requiring fast-track status that is specific to the subcutaneous form.

In a statement, Eisai and Biogen said a fast-track application has now been filed but kicks off a review period that could take up to 60 days to complete.

The filing of the less frequent intravenous dosing still gives the companies an opportunity to make one maintenance option available to patients. The filing draws on 24-month data from the clinical trials which suggests there is a benefit to staying on treatment even after amyloid plaques are resolved.

The idea is to maintain a concentration of Leqembi in the body that sustains the clearance of toxic amyloid ‘protofibrils’ which can continue to cause neuronal injury after the plaques are gone.

Studies have suggested that amyloid plaques start to reaccumulate after treatment with anti-amyloid stops – estimates are by around 3% to 4% per year – according to Biogen’s head of development Priya Singhal.

“Biomarkers…reflecting disease progression continue to accumulate as soon as patients are off drug,” she previously suggested on a conference call with analysts. She added: “Evidence points us to the fact that…continuing drug to some level is going to be important” while acknowledging that questions still remain about the frequency and duration of maintenance.

Leqembi is now approved in the US, Japan, and China, and is under regulatory review in Europe and other markets. In the EU, the review is also subject to a delay, after the EMA was forced to convene a new Scientific Advisory Group (SAG) on the drug after a legal ruling by the Court of Justice of the EU.

Sales have been slow to grow in the US, where it was approved first, and Eisai recorded just $7 million in sales in the last quarter of 2023. It has predicted that Leqembi could make almost $9 billion per year at its peak, but the pace of uptake has led some analysts to rein in their forecasts.