Biogen, Eisai Begin Submission of Subcutaneous Leqembi

Biogen and Eisai have begun a rolling submission of a biologics license application (BLA) to the FDA for a subcutaneous autoinjector for weekly dosing of Leqembi (lecanemab-irmb). The FDA has granted this a fast track designation. If approved, the Leqembi autoinjector could be used to administer the medication at home or at medical facilities.

An intravenous formulation of Leqembi is indicated to treat adults with early Alzheimer’s disease (AD). Leqembi has been on the market since January 2023 when it received an accelerated approval. It has a list price of $26,500 a year. The IV formulation of Leqembi received full approval in July 2023 based on phase 3 data from Eisai’s global Clarity AD clinical trial. In March 2024, Biogen and Eisai announced they had submitted a supplemental application for a monthly maintenance dose of the IV formulation of Leqembi.

The companies originally had aimed to submit the weekly subcutaneous formulation to the FDA in March 2024. But the FDA required an additional three-month immunogenicity data at the proposed maintenance dose of 360 mg

Weekly subcutaneous administration of Leqembi removed 14% more amyloid plaque in patients with Alzheimer’s disease than the biweekly intravenous formulation, according to data released at the annual Clinical Trials on Alzheimer’s Disease (CTAD) conference in October 2023. Additionally, 60% of the patients with early stage Alzheimer’s disease and who have low levels of the protein tau achieved cognitive improvement when treated with Leqembi.

The new data come from the open-label extension of the Clarity AD study. In a substudy, 72 patients received Leqembi for the first time as the subcutaneous formulation, and 322 patients received the IV formulation followed by subcutaneous administration. Amyloid in the brain was measured by PET scan at six months.

In addition, researchers conducted a post hoc analysis assessing patients with high vs. low levels of the tau protein in the brain, which indicates an earlier stage of the disease. In the patients with low levels of tau, 76% showed no deterioration of cognition after treatment with Leqembi, and 60% showed clinical improvement after 18 months of treatment in the primary endpoint.

In the Tau PET substudy, Leqembi suppressed the accumulation of tau in the medial temporal brain region in low-tau subpopulations, and in a broader range of brain regions in patients with higher levels. Researchers said this suggests that Leqemb treatment may have different effects on brain regions depending on the stage of the disease.

Systemic injection/infusion reactions are uncommon and mild with subcutaneous administration, and 8.1% of patients in the subcutaneous first administration had injection site reactions. Most were mild and moderate in severity consisting of redness, irritation, or swelling. Rates of amyloid-related imaging abnormalities (ARIA) were similar in both arms.

Related: Biogen to Stop Selling Alzheimer’s Drug Aduhelm

In January 2024, Biogen announced that stopped selling its Alzheimer’s drug Aduhelm (aducanumab-avwa) and will focus its resources on Leqembi and research of other treatments for Alzheimer’s disease.

Aduhelm had received accelerated approval from the FDA in June 2021, and Biogen was conducting post-marketing confirmatory ENVISION study. The company said in a press release it will stop the ENVISION and direct resources toward other Alzheimer’s programs, including an antisense oligonucleotide licensed from Ionis that targets tau (BIIB080) and an oral small molecule inhibitor of tau aggregation (BIIB113).

Biogen officials said it closed out the Aduhelm program in the fourth quarter of 2023 and ended the license with Neurimmune. In a Securities and Exchange Commission filing in November 2023, Biogen indicated that it had already eliminated is commercial infrastructure for Aduhelm, deprioritized of certain research and development programs. It had previously written off $275 million of inventory related to Aduhelm.