Leqembi OK’d as under-the-skin autoinjector for early Alzheimer’s
Approval applies to those receiving at least 1.5 years of intravenous dosing
The U.S. Food and Drug Administration (FDA) has approved Leqembi Iqlik (lecanemab-irmb), an under-the-skin autoinjector formulation for maintenance dosing in early Alzheimer’s disease.
The approval, announced by co-developers Biogen and Eisai, applies to those who first receive at least 1.5 years of the intravenous version.
The approval gives patients the option to continue infusions into a vein once every four weeks or start a weekly subcutaneous injection with the Leqembi Iqlik autoinjector, beginning in the U.S. on Oct. 6. Administered in about 15 seconds, the Leqembi Iqlik autoinjector has the potential to reduce the time and healthcare resources associated with intravenous dosing.
Eisai has now started a rolling application to approve Leqembi Iqlik for initiation dosing, the company announced in a second press release. With a rolling application, individual sections can be submitted when they’re ready, instead of a full application, which can help speed a drug’s approval. The application has been granted fast track status, which shortens the review process.
Alzheimer’s features a toxic buildup of amyloid-beta, which is thought to drive neurodegeneration and its related symptoms.
Leqembi is an antibody-based therapy that’s designed to promote the immune system’s clearance of amyloid-beta and slow disease progression. It targets insoluble clumps of the protein called amyloid plaques, but also amyloid protofibrils, which are soluble amyloid clumps believed to play a role in cognitive decline.
Leqembi won full approval in 2023 as an intravenous therapy for Alzheimer’s patients with mild cognitive impairment or who are in mild stages of dementia, collectively referred to as early Alzheimer’s. The agency this year approved a monthly intravenous maintenance dosing regimen for those who completed the twice-monthly initiation phase. The company asked the FDA to approve a weekly subcutaneous autoinjector version, dubbed Leqembi Iqlik (pronounced “I Click”), for maintenance dosing last year. With subcutaneous dosing, patients or trained caregivers can use the device at home, requiring less treatment time and no visit to an infusion center.
“The [subcutaneous] formulation also has the potential to reduce healthcare resources associated with [intravenous] maintenance dosing, such as preparation for infusion and nurse monitoring, while increasing infusion capacity for new eligible patients to begin initiation treatment and streamlining the overall [Alzheimer’s] treatment pathway,” the companies stated in their release.
Results of subcutaneous Leqembi testing
The application for subcutaneous Leqembi was based on data from the open-label extension of the Phase 3 Clarity AD trial (NCT03887455). That study, which served as the basis for Leqembi’s initial FDA approval, showed it slowed the decline in cognition and functional ability relative to a placebo.
A sub-study from Clarity AD evaluated a range of subcutaneous doses. Data showed transitioning to the weekly Leqembi Iqlik autoinjector (360 mg) after 1.5 years of the initiation dose maintained clinical and biomarker benefits comparable to continued intravenous dosing, according to Eisai and Biogen. Of the 49 patients who received a weekly subcutaneous maintenance dose, none had any local or bodywide injection-related adverse events.
While the safety profile across all subcutaneous doses was similar to that of the intravenous maintenance treatment, systemic reactions were much less common with subcutaneous dosing (1% vs. 26%). About 11% of patients had mild to moderate local reactions, such as redness, swelling, or itching at the injection site, which didn’t interfere with ongoing treatment. Moreover, less than 1% had mild systemic symptoms such as headache, fever, or fatigue.
Those receiving Leqembi, either subcutaneously or intravenously, had similar rates of amyloid-related imaging abnormalities, or ARIA, to the background rates in patients without treatment. ARIA, which are usually asymptomatic, can potentially have serious or life-threatening side effects that can include brain swelling or bleeding.
The companies also conducted additional studies, including a human factors study and a tolerability assessment of the device, to confirm its safety and effectiveness in the expected environments.
If the FDA approves Leqembi Iqlik for initial dosing, the autoinjector could be used to administer a once-weekly 500 mg starting dose as an alternative to biweekly intravenous dosing.
“This would expand the option for patients and care partners to receive Leqembi treatment from initiation to maintenance at home, offering a choice between [intravenous] and [subcutaneous] administration,” the company said.
Injection support will be available for Lequembi Iqlik. In addition, Eisai’s Patient Assistance Program (PAP) will help ensure access by providing the medicine at no cost to eligible patients. This includes uninsured and underinsured individuals, as well as Medicare beneficiaries, who meet financial need and other requirements.
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