Breakthrough Alzheimer’s Treatment LEQEMBI Receives FDA Approval for Traditional Use, Thanks to Eisai and BioArctic Partnership

BioArctic AB’s partner Eisai announced today that they have submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) in order to convert the Accelerated Approval of LEQEMBI™ (lecanemab-irmb[1]) 100 mg/mL injection for intravenous use to a traditional approval. The FDA granted Accelerated Approval of LEQEMBI on January 6, a groundbreaking monoclonal antibody designed to treat Alzheimer’s disease (AD) by targeting aggregated soluble and insoluble forms of amyloid beta (Aβ). LEQEMBI’s traditional approval is based on data from the confirmatory Phase 3 Clarity AD clinical trial, and it is recommended for patients with mild cognitive impairment or mild dementia stage of disease and confirmed presence of Aβ pathology.

The FDA granted accelerated approval to LEQEMBI, a medication for Alzheimer’s Disease, based on its ability to reduce the accumulation of Aβ plaques in the brain. Continued approval for this indication rested on the results of the Phase 3 Clarity AD clinical trial, which yielded highly statistically significant results that met both the primary and key secondary endpoints. These results, presented at the 2022 Clinical Trials on Alzheimer’s Disease conference and simultaneously published in the New England Journal of Medicine, further validated LEQEMBI’s potential in the fight against Alzheimer’s Disease.

Eisai is taking a major step forward in the global effort to provide access to lecanemab, a potential new treatment for a variety of diseases. In December 2022, the company began submitting data to the National Medical Products Administration (NMPA) of China for a Biologics License Application (BLA). Eisai is aiming to have filed marketing authorization applications for lecanemab in Japan and the European Union by the end of the first quarter of 2023 at the latest.

BioArctic is thrilled with their partner Eisai’s incredible commitment to making progress with their LEQEMBI sBLA submission to the FDA for accelerated approval. Alzheimer’s disease is a heartbreaking condition, and the sBLA submission for LEQEMBI brings us all closer to the possibility of a full FDA approval, and to finally being able to offer a new treatment option to the millions of people and families affected by this devastating disease.



LEQEMBI is an innovative treatment option for those with Alzheimer’s disease. Approved under an accelerated approval process, LEQEMBI helps to reduce amyloid beta plaques in patients with mild cognitive impairment or mild dementia stage of the disease. To ensure its effectiveness, clinical trials were conducted in this population. Those looking to start treatment with LEQEMBI should consider these stages of the disease; safety and effectiveness data are not available for earlier or later stages. To maintain approval, LEQEMBI must be proven to have a clinical benefit in a confirmatory trial.



Amyloid Related Imaging Abnormalities

Leukoencephalopathy due to Immunotherapy with Anti-CD20 Monoclonal Antibodies (LEQEMBI) can cause two types of amyloid-related imaging abnormalities: Edema (ARIA-E) and Hemosiderin Deposition (ARIA-H). ARIA-E appears on MRI as brain edema or sulcal effusions, while ARIA-H manifests as microhemorrhage and superficial siderosis. Although ARIA is typically asymptomatic, serious and even life-threatening events, such as seizure or status epilepticus, can arise as a result. Other symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Thankfully, these symptoms usually resolve over time.

ARIA monitoring and dose management guidelines

  • Before beginning treatment with LEQEMBI, it is important to have up-to-date brain magnetic resonance imaging (MRI) within the past year. To ensure the best outcomes, make sure to obtain an MRI prior to the 5th, 7th, and 14th infusions.
  • When managing ARIA-E and ARIA-H in patients, determining the appropriate dose can be tricky. Clinical symptoms and radiographic severity must be considered to assess whether the treatment should continue, be altered, or discontinued altogether. At the end of the day, it is up to the clinician to use their best judgment in deciding the most suitable course of action for the patient.
  • During the initial 14 weeks of LEQEMBI treatment, extra care should be taken to monitor for signs of ARIA, such as symptoms indicative of the condition. If any symptoms are noticed, a medical evaluation, including an MRI if necessary, should be carried out. In the event of ARIA being detected, further medical examination should be conducted before continuing with the treatment.
  • Patients who have continued dosing through symptomatic ARIA-E or through asymptomatic yet radiographically severe ARIA-E have had no experience. However, for those who have continued dosing through asymptomatic yet radiographically mild to moderate ARIA-E, there is limited experience. Additionally, for those who have experienced recurrent ARIA-E, there are also limited data regarding dosing.

Incidence of ARIA

  • In Study 1 (Phase 2b), symptomatic ARIA-E was observed in 3% (5/161) of LEQEMBI-treated patients. Fortunately, the clinical symptoms associated with ARIA were found to resolve in 80% of patients during the period of observation.
  • In the LEQEMBI group, ARIA was observed in 12% of cases (20/161), including those who were asymptomatic. In the placebo group, ARIA was observed in 5% of cases (13/245). Similarly, ARIA-E was observed in 10% of LEQEMBI cases (16/161), and just 1% of placebo cases (2/245). For ARIA-H, 6% of LEQEMBI cases were observed (10/161), which was the same as the placebo group (5%, 12/245). There was no difference in isolated ARIA-H between LEQEMBI and placebo.
  • In the LEQEMBI treatment study, one patient experienced an intracerebral hemorrhage of 1 cm or more in diameter, while there were no reported cases in the placebo group. Other studies have also documented the occurrence of intracerebral hemorrhage, including fatal events, in patients who took LEQEMBI.

Apolipoprotein E ε4 (ApoE ε4) carrier status and risk of ARIA

  • In a Phase 2b study, only 6% (10/161) of patients in the LEQEMBI group were homozygous for the ApoE ε4 gene, with 24% (39/161) being heterozygotes and 70% (112/161) being non-carriers.
  • Patients treated with LEQEMBI were found to have a higher incidence of ARIA when compared to those who did not carry the ApoE ε4 gene. Out of the five LEQEMBI-treated patients who experienced symptomatic ARIA, four were ApoE ε4 homozygotes, two of whom reported severe symptoms. This increased incWhen it comes to managing ARIA, there is no difference between ApoE ε4 carriers and non-carriers – the same recommendations apply to both.idence of symptomatic and overall ARIA in ApoE ε4 homozygotes compared to heterozygotes and noncarriers in LEQEMBI-treated patients has been supported by other studies.
  • When it comes to managing ARIA, there is no difference between ApoE ε4 carriers and non-carriers – the same recommendations apply to both.
  • When considering treating with LEQEMBI, it may be beneficial to test for ApoE ε4 status in order to gain a better understanding of the risk of developing ARIA. By knowing this information, you can make an informed decision about your treatment options.

Radiographic findings

LEQEMBI treatment has been associated with ARIA-E (edema) and ARIA-H (microhemorrhage) events in a small number of patients. Of those affected with ARIA-E, the maximum radiographic severity was mild in 4% (7/161), moderate in 4% (7/161), and severe in 1% (2/161). Fortunately, resolution on MRI was witnessed in the majority of those affected, with 62% resolved by 12 weeks, 81% resolved by 21 weeks, and 94% overall after detection. For those affected with ARIA-H, the maximum radiographic severity was also mild in 4% (7/161) and severe in 1% (2/161); 1 of the 10 patients with ARIA-H had mild superficial siderosis.

Concomitant antithrombotic medication and other risk factors for intra-cerebral hemorrhage

Patients were excluded from enrolling in Study 1 (Phase 2b) at baseline if they had been taking anticoagulant medications. However, those using antiplatelet medications such as aspirin and clopidogrel were still eligible. If anticoagulant medication was needed to treat an existing medical event that required treatment for no more than four weeks, treatment with LEQEMBI was to be put on hold.

Aspirin was the most common antithrombotic medication prescribed, but few patients were exposed to other antiplatelet drugs or anticoagulants. This makes it difficult to draw conclusions about the risk of ARIA or intracerebral hemorrhage with these other medications. However, intracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI, so extra caution should be taken when considering combining antithrombotic medications or a thrombolytic agent with LEQEMBI.

Patients with a prior history of 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, or severe small vessel or white matter disease were not eligible to participate in Study 1 (Phase 2b). Therefore, these risk factors should be taken into consideration when considering the use of LEQEMBI.

Infusion-related reactions

Patients treated with LEQEMBI experienced infusion-related reactions in 20% of cases (32/161), in comparison to only 3% (8/245) for placebo. Of the reactions, 88% (28/32) occurred with the first infusion, and were generally mild to moderate in severity. In rare cases, these reactions caused patients to discontinue treatment (2%, 4/161). Symptoms included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.

LEQEMBI-treated patients showed a marked difference in their blood cell count levels compared to those on placebo – 38% of LEQEMBI patients had a transient decrease in lymphocyte counts to less than 0.9 x109/L, while only 2% of those on placebo had the same decrease. Similarly, 22% of LEQEMBI-treated patients had a transient increase in neutrophil counts to greater than 7.9 x109/L, compared to just 1% of those on placebo.

In the event of an infusion-related reaction, appropriate therapy may be initiated and the infusion rate reduced or discontinued. To avoid such reactions in the future, prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids can be considered before the next infusion.


In Study 1 (Phase 2b), LEQEMBI-treated patients experienced an adverse reaction rate of 15%, compared to only 6% of placebo-treated patients. Infusion-related reactions were the most common cause of discontinuation, leading 2% (4/161) of LEQEMBI-treated patients to stop treatment, compared to just 1% (2/245) of placebo-treated patients.

Patients treated with LEQEMBI experienced much higher rates of adverse reactions than those taking the placebo. The most common adverse reactions reported in more than 5% of LEQEMBI patients, and more than 2% higher than placebo patients, were infusion-related reactions (20% vs. 3%), headache (14% vs. 10%), ARIA-E (10% vs. 1%), cough (9% vs. 5%) and diarrhea (8% vs. 5%).

About LEQEMBI™ (lecanemab-irmb)

LEQEMBI™ (lecanemab-irmb) is a groundbreaking treatment for Alzheimer’s Disease (AD). It is a humanized IgG1 monoclonal antibody that targets aggregated forms of amyloid-beta (Aβ) to help ameliorate the effects of AD. Based on the results of the Clarity AD clinical trial, LEQEMBI has been approved under accelerated approval as a treatment for mild cognitive impairment or mild dementia in the U.S. Not only did LEQEMBI meet its primary endpoint and all key secondary endpoints with highly statistically significant results, but it also demonstrated an expected profile of Amyloid-Related Imaging Abnormalities (ARIA) incidence. LEQEMBI is an exciting new development in the fight against Alzheimer’s Disease.

In December 2022, Eisai took the monumental step of submitting data to the National Medical Products Administration (NMPA) of China for the BLA of lecanemab, a strategically developed research alliance between Eisai and BioArctic. With plans to file for marketing authorization applications of lecanemab in Japan and the EU by the end of the first quarter of 2023, this is expected to be a groundbreaking development that could revolutionize the industry.

Eisai is currently conducting a groundbreaking Phase 3 clinical study, AHEAD 3-45, to explore the potential of a new treatment for preclinical Alzheimer’s disease. This public-private partnership between the Alzheimer’s Clinical Trial Consortium, the National Institute on Aging, and the pharmaceutical giants Eisai and Biogen is targeting individuals with clinically normal brains but intermediate or elevated levels of amyloid. It is hoped that this study will bring new hope to those who have been diagnosed with preclinical Alzheimer’s.

The DIAN-TU, led by Washington University School of Medicine in St. Louis, is currently conducting the Tau NexGen clinical study for Dominantly Inherited Alzheimer’s Disease (DIAD) since January 2022. Eisai has already completed a LEQEMBI subcutaneous bioavailability study and is now assessing subcutaneous dosing in the Clarity AD open label extension study. This is an exciting step forward in the medical world’s understanding of DIAD and its treatment.

About Amyloid-Related Imaging Abnormalities (ARIA)

ARIA is an important adverse event of amyloid-lowering therapies that must be closely monitored and managed during treatment. It is most commonly seen as temporary swelling/effusion (ARIA-E) in certain areas of the brain, which usually resolves over time. Some individuals may also experience small spots of bleeding in or on the surface of the brain (ARIA-H). While many with ARIA-E do not experience any symptoms, others may suffer from headaches, confusion, dizziness, vision changes, and nausea. It is important to be aware of the effects of ARIA and to seek medical attention if any symptoms arise.

About the collaboration between BioArctic and Eisai

BioArctic and Eisai have been collaborating since 2005 to develop and commercialize drugs that treat Alzheimer’s disease. In December 2007, the two companies signed a Development and Commercialization Agreement for the lecanemab antibody. Additionally, in May 2015, they signed a Development and Commercialization Agreement for the antibody BAN2401 backup for Alzheimer’s disease. In March 2014, Eisai and Biogen entered into a joint development and commercialization agreement for lecanemab, with Eisai taking the lead on clinical development, market approval, and commercialization. BioArctic has the rights to commercialize lecanemab in the Nordic region and is in the process of preparing for such commercialization with Eisai. As part of the agreement, BioArctic has no development costs for lecanemab in Alzheimer’s disease and is entitled to payments in connection with regulatory filings, approvals, and sales milestones, as well as royalties on global sales.

About BioArctic AB

BioArctic AB (publ) is a Swedish biopharma company on a mission to develop disease-modifying treatments for neurodegenerative diseases such as Alzheimer’s, Parkinson’s and ALS. With innovative research from Uppsala University as its foundation, BioArctic is dedicated to creating treatments that address high unmet medical needs. The company’s collaborative partnerships with universities and global pharmaceutical companies, as well as its strategic partnership with Eisai in Alzheimer’s disease, are essential to its research efforts. Its project portfolio combines fully funded initiatives with its own innovative projects with promising market and out-licensing potential. BioArctic’s Class B share is traded on Nasdaq Stockholm Mid Cap (ticker: BIOA B).

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