Last week Esai and Biogen (Esai/BIIB) moved a step closer to getting full approval for their Alzheimer Disease (AD) therapeutic, Leqembi (lecanemab) (FIG. 1), with a vote of confidence from an FDA Advisory Committee (AdCom).^1
Leqembi is the second beta amyloid antibody that received accelerated conditional approval by the FDA for the treatment of AD. The first beta amyloid antibody to receive accelerated approval by the FDA, Esai/BIIB's Aduhelm turned out to be a commercial and public relations disaster for BIIB and the FDA, and to a certain extent, beta amyloid antibodies for the treatment of AD. However, Leqembi's recent Phase 3 data report outs, as well as Phase 3 data released by Eli Lilly on its competing amyloid beta antibody therapeutic, donanemab, appear to establish that at least some beta amyloid antibodies can slow the progression of AD in patients with mild to moderate disease (See FIG. 2 below (from Esai FDA AdComm Briefing doc June 2023).
Amyloid beta therapeutics come with an increased risk of brain swelling (ARIA-E) and bleeding (ARIA-H), which can be serious, and occasionally is fatal. The current prescribing information for lecanemab includes a warning for the risk of ARIA and provides recommendations for monitoring and dose management guidelines.^2 It also describes the increased risk of ARIA in ApoE ε4 homozygotes compared to heterozygotes and noncarriers (See FIG. 10 below from the Esai AdComm presentation), and the need to exercise additional caution when considering the administration of antithrombotics or a thrombolytic agent with lecanemab.
However, at least the FDA and its recent Leqembi AdCom appear convinced that at least for Leqembi, the benefits outweigh the risks.
The likely full approval of Leqembi by the FDA later this month, and the possible approval of donanemab over the next year or so if things go as planned for LLY with their FDA review, should be game changers for the use of these drugs by AD patients.^3 This is because CMS has acknowledged that unlike conditionally approved beta amyloid drugs, they will cover the majority of the cost of beta amyloid drugs if they get full approval for U.S. Medicare patients. Thus, it is expected to 1,000s and likely 10,000s of U.S. AD patients will likely be taking lecanamab or donanemab in the coming years, generating billions of dollars of revenue for these drugs. This will be the start of a new and exciting era in the treatment of AD with the first widely used drugs that slow the progression of this debilitating disease.
This new era for AD treatment, opens up a set of opportunities for antibody discovery companies, biotherapeutics companies, clinical diagnostics companies, clinical research organizations, and patient recruitment companies. To read about 8 opportunities that we've identified from this fundamental change in Alzheimer's care, CLICK HERE to sign up to get our free report.
^1 The AdCom voted a 6-0 that clinical efficacy was sufficiently demonstrated by Esai/BIIB's Phase 3 trial and in their discussion of genetic factors and safety, appeared to endorse the current label of Leqembi, or something similar. Leqembi was conditionally approved in January under an accelerated pathway using a surrogate marker (removal of beta amyloid plaques).
^2 From current Leqembi label: “17 PATIENT COUNSELING INFORMATION
Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide). Amyloid Related Imaging Abnormalities
Inform patients that LEQEMBI may cause Amyloid Related Imaging Abnormalities or “ARIA”. ARIA most commonly presents as a temporary swelling in areas of the brain that usually resolves over time. Some people may also have small spots of bleeding in or on the surface of the brain. Inform patients that most people with swelling in areas of the brain do not experience symptoms, however, some people may experience symptoms such as headache, confusion, dizziness, vision changes, nausea, aphasia, weakness, or seizure. Instruct patients
to notify their healthcare provider if these symptoms occur. Inform patients that events of intracerebral hemorrhage greater than 1 cm in diameter have been reported infrequently in patients taking LEQEMBI, and that the use of antithrombotic or thrombolytic medications while taking LEQEMBI may increase the risk of bleeding in the brain. Notify patients that their healthcare provider will perform MRI scans to monitor for ARIA [see Warnings and Precautions (5.1)]. Inform patients that although ARIA can occur in any patient treated with LEQEMBI, there is an increased risk in patients who are ApoE ε4 homozygotes, and that there is a test available to determine ApoE ε4 genotype.
Advise patients that the Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET) is a voluntary provider-enrolled patient registry that collects information on treatments for Alzheimer’s disease, including LEQEMBI. Encourage patients to participate in the ALZ-NET registry [see Warnings and Precautions (5.1)].”
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Article History Original published: 6/13/23