LuMind IDSC issues statement following FDA full approval of Leqembi™ to treat early-stage Alzheimer’s disease
July 7, 2023
In a groundbreaking decision that signals new hope for people with Alzheimer’s disease, yesterday the U.S. Food & Drug Administration (FDA) granted full approval for Leqembi, a drug that slows the progression of Alzheimer’s disease.
Leqembi, which was co-developed by biopharmaceutical companies, Eisai and Biogen, is approved to treat patients in the early dementia stage of Alzheimer’s disease who also have “confirmed presence of amyloid beta pathology” in the brain. Read more about Leqembi’s conditional approval in January 2023 here.
For the 1.5 million people in the early stages of Alzheimer’s disease, the FDA decision is a reason to celebrate. Not only is Leqembi the first anti-amyloid drug to receive full approval from the FDA, this drug has also demonstrated better and more consistent clinical trial results than its predecessor, Aduhelm™, which was conditionally approved for use in June 2021.
Safety trials of Leqembi within the general population showed treatment with the drug was generally safe, although all antibodies that clear amyloid plaques from the brain are associated with risks of brain bleeding and brain swelling. Determining the safety of a newly developed drug is always complex, especially for drugs that impact the brain.
What does this important FDA decision mean for people with Down syndrome and their families?
While the approval of Leqembi is an unequivocal high point in the 20-year trajectory of Alzheimer’s disease research, questions persist as to whether the new drug is safe for, or will someday be accessible to, people with Down syndrome. No one with Down syndrome was included in the Leqembi clinical trials to date, so researchers cannot conclusively determine the drug’s safety for the Down syndrome population, and clinicians warn that doctors should not prescribe Leqembi to someone with Down syndrome until specific safety trials are complete.
The absence of people with Down syndrome from the Leqembi trials is significant, because trial data showed that some neurotypical Alzheimer’s disease patients who took Leqembi experienced an increase in brain swelling and bleeding due to the existence of cerebral amyloid angiopathy (CAA). CAA means that there are amyloid plaques in the brain’s blood vessels, a condition that is more common among people with Down syndrome.
CAA is caused by amyloid plaque adhering to blood vessels in the brain and it occurs naturally, to some degree, as a person ages. But because people with Down syndrome produce more amyloid, they are at a significantly higher risk of developing higher levels of CAA and therefore could be at higher risk for brain bleeds and swelling, especially after anti-amyloid drug treatment.
The risk of CAA is particularly important, because anti-amyloid drugs like Leqembi are designed to remove amyloid plaques. When amyloid plaques are removed from the cerebral blood vessels, the vessels are weakened. CAA can cause the weakening of blood vessels and subsequent microhemorrhages, which often go undetected and can, over time, cause severe cognitive decline and more frequent brain hemorrhages.
Earlier this year, LuMind IDSC and the National Task Group on Intellectual Disabilities and Dementia (NTG) convened a panel of 20 international Down syndrome and Alzheimer’s experts who called for safety studies to be conducted as soon as possible to specifically address the risk associated with CAA in the brain of a person with Down syndrome being treated with an anti-amyloid drug such as Leqembi.
ASSESSMENT TOOL ADAPTATIONS
The assessment tools currently used to measure cognitive and functional changes related to Alzheimer’s disease in the general population are not applicable for adults with Down syndrome. Specific assessments, that have already been adapted for Down syndrome and are available now, should be used in safety clinical trials and to identify individuals with Down syndrome in the early stages of Alzheimer’s disease who would benefit from Leqembi therapy.
ONCE SAFETY IS DETERMINED: ACCESS & REIMBURSEMENT
If/when Leqembi or another anti-amyloid drug is determined by clinical trials to be safe to administer to people with Down syndrome, the community will face policy and procedural hurdles before doctors can prescribe the drugs to people with Down syndrome.
Drug formulary committees in each state decide under what circumstances new drugs can be prescribed by doctors. The formulary committees issue “prior authorization” standards that vary from state to state. The prior authorizations include things like: the age of the patient in order to receive the drug, what their diagnosis and prognosis are, as well as other factors that determine the eligibility of a patient to receive the drug.
Currently, the “prior authorization” criteria, issued by state formulary committees to guide doctors as they prescribe these drugs, excludes adults with Down syndrome. The current criteria do not mention adaptations or reasonable adjustments to be made that would enable adults with Down syndrome access to these treatments once they are deemed appropriate for use.
LuMind IDSC and NTG convened a panel of international experts to formally request policy changes from state and federal agencies. Read more about the panel and the consensus statement demanding change here.
In addition to the issue of eligibility is the complex issue of reimbursement for individuals covered by Medicare or Medicaid. Immediately following the FDA’s approval announcement on Thursday July 6, 2023, the federal Centers for Medicare and Medicaid (CMS) provided some clarification as to the establishment of federal a registry requirement, which compels doctors prescribing Leqembi to submit data to a central registry.
Additional CMS policies will determine how insurance companies and state-funded systems Medicaid and Medicare will cover the very high cost of administering Leqembi.
If I am an adult with Down syndrome who is eligible for Leqembi therapy, does LuMind IDSC recommend I take the drug?
As with any medical and therapeutic treatments, the ultimate decision to take a drug should be made by individuals, their families, and their trusted medical team. Due to the potential safety considerations outlined above, LuMind IDSC does not recommend people with Down syndrome take Leqembi at this time, except in the case of a safety clinical trial. This guidance aligns with the recommendations of the LuMind IDSC/NTG expert panel of medical doctors and clinicians, and with recently published appropriate use criteria for Leqembi.
LuMind IDSC and our collaborators will continuously advocate with the pharmaceutical industry and with federal agencies for Down syndrome safety trials to be conducted as soon as possible with anti-amyloid treatments.
We will provide updates if and when a safety trial for Leqembi or another Alzheimer’s disease therapy is confirmed.
What are the next steps?
LuMind IDSC and the Down syndrome community will continue to advocate for clinical research and policy/protocol adaptations in adults with Down syndrome for Leqembi and other anti-amyloid antibody therapies.
Adaptations and adjustments will ensure that future studies include adults with Down syndrome, and that people with Down syndrome receive the same levels of access to this groundbreaking treatment as will every other American with early Alzheimer’s disease.
LuMind IDSC will update the community as we learn how Leqembi will be reimbursed, the potential for safety trials for people with Down syndrome, and what access our community will have to this therapy.
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