Eisai Submits sBLA for Monthly Intravenous Maintenance Dosing of Alzheimer Therapy Lecanemab
The company also submitted a request for a fast track designation specific to a subcutaneous version of lecanemab and is expected to hear back within 60 days from March 2024.
Reisa Sperling, MD
According to an announcement from Eisai and Biogen, the companies have officially submitted a supplemental biologics license application (sBLA) for a new monthly intravenous (IV) maintenance dosing for lecanemab-irmb (Leqembi), its FDA-approved therapy for early-stage Alzheimer disease (AD). Those who’ve already completed the biweekly IV initiation phase are now eligible to receive a monthly IV does that maintains effective drug concentration to sustain the clearance of highly toxic protofibrils.1
Lecanemab, a humanized immunoglobulin gamma 1 monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid-ß, was approved in July 2023 in 100 mg/mL injections for IV use. In the newly submitted sBLA, the companies included data from Study 201 (NCT01767311), a phase 2 trial, and its open-label extension (OLE), as well as the phase 3 Clarity AD trial (NCT03887455), the study that lecanemab was traditionally approved on, and its OLE.
The companies also planned to submit a BLA for a weekly maintenance therapy dose of 360 mg using a subcutaneous (SC) administration; however, the FDA brushed back, claiming it needed a fast track designation specific for the SC formulation to proceed with the review. Following the guidance, Eisai submitted a request for fast track designation for the SC formulation and noted it will initiate a rolling submission should the FDA grant this designation. A decision on this designation is expected to come within 60 days of the March 2024 submission.
At the 2023 Clinical Trials on Alzheimer’s Disease (CTAD) Conference, data from the OLE of Clarity AD showed that a novel SC form of lecanemab resulted in greater amyloid plaque removal than biweekly IV administration. After 6 months of treatment, a subgroup of patients demonstrated a 14% increased amyloid plaque removal with the SC method than IV administration, the administration for which it was FDA-approved under.2
Presented by Reisa Sperling, MD, a neurologist at Brigham and Women’s Hospital, Harvard Medical School, the data comprised of 72 patients with early AD who received lecanemab for the first time in a subcutaneous way and 322 patients who received IV lecanemab in the Clarity AD core study followed by SC administration in the substudy. All told, investigators observed reductions of –40.3 (±2.27) centiloids at 6 months for newly treated paitents on SC lecanemab vs reductions of –35.4 (±1.14) centiloids for those on IV administration. In addition, the weekly SC pharmacokinetic area under the curve were 11% higher than the biweekly IV formulation.
In the Clarity AD core study, 12.6%, 17.3%, and 8.9% of patients reported ARIA-edema, ARIA-H (cerebral microhemorrhage because of ARIA, cerebral hemorrhage, and brain surface hemosiderin deposition) and ARIA-H alone, respectively, with intravenous lecanemab. Among the subgroup of 72 patients on subcutaneous lecanemab in the new analysis, investigators observed incidence rates of 16.7%, 22.2%, and 8.3%, respectively; however, Eisai noted that no exact comparison was made because of the sample size of individuals.
