09 January 2023 | Monday | News
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BioArctic AB's (publ) (Nasdaq Stockholm: BIOA B) partner Eisai announced today that under the Accelerated Approval pathway the U.S. Food and Drug Administration (FDA) has approved lecanemab-irmb (Brand Name in the U.S.: LEQEMBI™) 100 mg/mL injection for intravenous use, a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble ("protofibrils") and insoluble forms of amyloid beta (Aβ) for the treatment of Alzheimer's disease (AD). The accelerated approval is based on Phase 2b data in early AD patients which demonstrated that LEQEMBI reduced the accumulation of Aβ plaque in the brain, a defining feature of AD. Using the recently published data from the large global confirmatory Phase 3 clinical trial, Clarity AD, Eisai will work quickly to file a Supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway. The approval of lecanemab-irmb by the FDA entitles BioArctic to a milestone payment of MEUR 25 from Eisai.
LEQEMBI is indicated for the treatment of Alzheimer's disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
Dosage and administration (patient selection, dosing instructions, monitoring and dosing interruption for ARIA)
The recommended dosage of LEQEMBI is 10 mg/kg administered intravenously once every two weeks to eligible patients with confirmed presence of Aβ pathology prior to initiating treatment. Enhanced clinical vigilance for amyloid-related imaging abnormalities (ARIA) is recommended during the first 14 weeks of treatment with LEQEMBI. Baseline, recent (within one year) brain MRI prior to initiating treatment with LEQEMBI and periodic monitoring with MRI prior to the 5th, 7th, and 14th infusions are obtained.
The safety of LEQEMBI has been evaluated in 763 patients who received at least one dose of LEQEMBI. The most common adverse reactions reported in at least 5% of patients treated with LEQEMBI 10 mg/kg biweekly (N=161) and at least 2% higher incidence than patients on placebo (N=245) were infusion-related reactions (LEQEMBI, 20%; placebo, 3%), headache (LEQEMBI, 14%; placebo, 10%), ARIA-E (LEQEMBI, 10%; placebo, 1%), cough (LEQEMBI, 9%; placebo, 5%) and diarrhea (LEQEMBI, 8%; placebo, 5%). The most common adverse reaction leading to discontinuation of LEQEMBI was infusion-related reactions which happened in 2% (4/161) of patients treated with LEQEMBI compared to 1% (2/245) of patients on placebo.
Concomitant antithrombotic medication and other risk factors for intra-cerebral hemorrhage
In Phase 2b, patients who received LEQEMBI and an antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) did not have an increased risk of ARIA-H compared to patients who received placebo and an antithrombotic medication. The majority of exposures to antithrombotic medications were to aspirin; few patients were exposed to other antiplatelet drugs or anticoagulants, limiting any meaningful conclusions about the risk of ARIA or intracerebral hemorrhage in patients taking other antiplatelet drugs or anticoagulants. Because intracerebral hemorrhages greater than 1 cm in diameter have been observed in patients taking LEQEMBI, additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI. Additionally, patients were excluded from enrollment in Phase 2b for the following risk factors for intracerebral hemorrhage: prior cerebral hemorrhage greater than 1 cm in greatest diameter, more than 4 microhemorrhages, superficial siderosis, evidence of vasogenic edema, evidence of cerebral contusion, aneurysm, vascular malformation, infective lesions, multiple lacunar infarcts or stroke involving a major vascular territory, and severe small vessel or white matter disease. Caution should be exercised when considering the use of LEQEMBI in patients with these risk factors.
"The FDA's approval of LEQEMBI under the Accelerated Approval pathway is an important milestone not only for BioArctic and our partner Eisai, but for the whole field as well as for patients, families and caregivers who can now benefit from the more than 20 years of research and development that lies behind this achievement. We are impressed by our partner Eisai's excellent work with LEQEMBI and are proud of our long-standing relationship that has led us to today's announcement," said Gunilla Osswald, CEO at BioArctic.
LEQEMBI's access and initiatives to support people living with Alzheimer's disease
The Eisai Patient Support Program will be available to offer several support programs to help patients and care partners. Dedicated Patient Navigators will work directly with patients and families to navigate treatment and coverage for eligible and appropriate patients and to help with what to expect regarding insurance coverage, co-pay and patient access programs. To learn more visit LEQEMBI.com, call 1-833-4-LEQEMBI (1-833-453-7362), Monday-Friday, 8 a.m. to 8 p.m. Eastern Time or by fax at 1-833-770-7017.
In addition, to support access to LEQEMBI for certain financially disadvantaged patients, Eisai's Patient Assistance Program (PAP) will provide LEQEMBI at no cost, for eligible uninsured and underinsured patients, including Medicare beneficiaries, who meet financial need and other program criteria.
Eisai has stated that they will continue to engage constructively with various payors, including the Centers for Medicare and Medicaid (CMS), TRICARE, the U.S. Veteran's Health Administration and private health insurance companies to ensure appropriate beneficiaries have access to this new therapy. Currently Medicare patients do not have access to LEQEMBI. Medicaid sole beneficiaries who are diagnosed by a healthcare professional with early AD and with confirmed presence of amyloid plaque in the brain will have access to LEQEMBI under the Medicaid program post accelerated approval, depending on individual state processes.
Furthermore, Eisai is developing a multi-faceted educational initiative to further advance the understanding in the AD healthcare community of the real-world management and monitoring of ARIA. This initiative, Understanding ARIA™, will provide resources and programs that will include peer-to-peer education, individual and group educational sessions and subject-matter-expert evaluation of historical case studies. Understanding ARIA will include engagements with leading experts in medical imaging as well as major professional societies. Initial resources will be available by January 2023.
LEQEMBI will be available during or before the week of January 23, 2023. Eisai has announced the U.S. pricing and rationale for LEQEMBI today in a separate news release. Eisai has based on a health economic analysis estimated the yearly societal value of Leqembi to be 37,600 USD per patient in the US. Eisai has decided to set the US launch price for Leqembi to 26,500 USD per year for the average patient, aiming to promote broader patient access, reduce overall financial burden and support health system sustainability.
Eisai has also issued a separate news release today regarding Eisai´s commitment to scientific evidence and patient safety. Both these news releases can be found on Eisai's website.
Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority. BioArctic has right to commercialize lecanemab in the Nordic under certain conditions and is currently preparing for commercialization in the Nordics together with Eisai.
INDICATION, dosage and administration, and important safety information in the U.S.
LEQEMBI is indicated for the treatment of Alzheimer's disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Amyloid Related Imaging Abnormalities
LEQEMBI can cause amyloid related imaging abnormalities-edema (ARIA-E) and -hemosiderin deposition (ARIA-H) ARIA-E can be observed on MRI as a brain edema or sulcal effusions, and ARIA-H as microhemorrhage and superficial siderosis. ARIA is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time.
ARIA monitoring and dose management guidelines
Incidence of ARIA
Apolipoprotein E ε4 (ApoE ε4) carrier status and risk of ARIA
Concomitant antithrombotic medication and other risk factors for intra-cerebral hemorrhage