The controversial anti-Alzheimers drug aducanumab may have just started the assessment process for TGA approval in Australia but there is already an application for public funding of the tests for amyloid positivity that will decide who is eligible for the drug if and when it is listed on the PBS.
The Medicare Service Advisory Committee (MSAC) has released preliminary details of the model in which patients with a diagnosis of early stage Alzheimer’s Disease (AD) would be eligible for access to PBS subsidised aducanumab treatment if they have amyloid beta (Aβ) deposition in the brain confirmed by PET scanning or CSF AD biomarker testing.
The TGA accepted Biogen’s aducanumab for evaluation in April 2021, and it received accelerated approval by the US Food and Drug Administration (FDA) in June 2021.
However the decision was disputed by several members of the FDA’s Peripheral and CNS Advisory Committee who resigned and described the approval as “the culmination of a highly unusual regulatory process” because it was based on the surrogate outcome of beta amyloid lowering rather than the drug’s “highly uncertain clinical impact”.
Meanwhile as the drug undergoes the Australian regulatory process, the application for testing foresees a model in which specialists will assess patients for aducanumab treatment if they have a diagnosis of “early stage” Alzheimer’s disease (AD), comprising mild cognitive impairment (MCI) due to AD/prodromal AD, or mild AD dementia.
The proposed treatment algorithm see patients with suspected AD referred by GPs to a memory clinic, gerontologist, or specialist in dementia.
Patients would be eligible for either Aβ PET scanning or CSF AD biomarker testing after having undergone clinical assessment by a specialist to establish a diagnosis of early stage AD.
“The tests are proposed to confirm the presence of Aβ deposition in the brain and hence AD pathology as the underlying cause of the condition. The two proposed tests are presented as alternative options to determine eligibility for aducanumab treatment and are intended to be mutually exclusive. Only one test option per patient would be reimbursed to determine aducanumab treatment eligibility and testing frequency is once per lifetime,” the application notes.
Patients who were “amyloid-positive” would be eligible for aducanumab, which the application describes as a human, anti-Aβ immunoglobulin G1 monoclonal antibody that selectively binds to Aβ fibrils and soluble oligomers reducing the amount of Aβ, including the number of amyloid plaques, present in the brain.”
“It is proposed that this may slow neurodegeneration and reduce disease progression,” it adds.
Aducanumab would be administered via intravenous infusion once a month.
The application notes that patients would require gradual drug dose escalation with aducanumab rand MRI monitoring to reduce the risk of amyloid-related imaging abnormality-(o)edema (ARIA-E) and amyloid-related imaging abnormality-haemorrhage (ARIA-H).
“The MRI signal changes in the brain observed in ARIA-E are thought to represent vasogenic oedema, while those observed in ARIA-H range from haemosiderin deposits to microhaemorrhages and macrohaemorrhages,” it notes.
In its report, MSAC notes that there are currently 85 Medicare eligible PET scanning facilities in Australia, but Aβ PET scanning is not currently funded on the MBS.The proposed fee is $918.
The numbers early stage AD patients in Australia who would likely access the testing services are redacted from the report.
A recent report by the ABC stated that aducanumab was estimated to cost $72,000 a year, and adding on regular MRIs to monitor the risk of ARIA would significantly increase the costs to taxpayers.