Alzheimer disease infusion clinic booking request

Overview

This clinic is for patients referred by specialist neurologists, geriatricians and psychiatrists. It is a triage clinic for patients who are to be considered to be potentially eligible for the new Alzheimer disease anti-amyloid antibody therapies. Patients will also need a GP referral but GP assessment will not be sufficient to be seen.

Please note that at a minimum, patients need to:

• Have mild cognitive impairment or mild dementia due to Alzheimer disease
• Atypical presentations due to Alzheimer disease will be considered if still fulfil the MCI or mild dementia functional conditions
• Apolipoprotein genotyping status done and NOT be homozygous for E4 (ie E4E4 status)
• Have had a recent brain MRI done (within 6 months of our assessment) to exclude significant white matter disease (Fazekas 3), infarctions, haemorrhages (ie > 5 microhaemorrhages on SWI, > 2 on GRE, lobar, siderosis or subarachnoid haemorrhage) or contraindications to further MRIs (especially pacemakers, etc)
• Do not have unstable medical conditions including active cancer, liver, renal, heart disease, etc

It is estimated that only about 10-15% of patients who are referred will actually be eligible for infusions through our service, since there are significant risks of this treatment. Please review the detailed eligibility criteria below carefully before considering requesting an appointment.

The therapy to be offered is donanemab (Kisunla) which was approved by the Australian TGA on 22/5/2025, though other therapies may be available (eg lecanemab [Lequembi] which may be available under a Special Access Scheme or if an appeal is upheld in future).

A patient handout summarising this information is available here: Patient information brochure.

Donanemab

Donanemab is for people with early stages of Alzheimer disease before symptoms require much daily support, i.e. patients with mild cognitive impairment or mild dementia. Once Alzheimer disease progresses, donanemab may no longer be effective so consideration of treatment as soon as possible is important. The USA FDA and now Australian TGA has set guidelines on who will be eligible to receive this treatment. Only individuals who meet these criteria will be considered to receive it in our service. These guidelines are based on the trials undertaken with this medication and the criteria set by the TGA (which excludes patients with 2 copies of the apolipoprotein E4 gene).

Donanemab Trailblazer AD trial

Donanemab underwent several trials including the phase 3 TRAILBLAZER trial published in the JAMA on 8 Aug 2023. It was a double-blind placebo-controlled randomized trial of 1736 participants with ~50% on 10mg/kg donanemab and 50% on placebo every 4 weeks for 18 months. Amyloid is the target of the antibody.

It is given by infusion (into a vein via an intravenous drip) over about 30 minutes (+ 1 hour post-infusion observation). See Prescribing Information.

Participants were eligible if:

• They had mild cognitive impairment or mild dementia due to Alzheimer disease
• Were age 60-85 years
• There was minimal functional impairment
• Mini-mental state examination (MMSE) score was 20-28 or above

Participants were NOT eligible if:

• There was MRI evidence of significant brain haemorrhages (including ≥ 4 microbleeds, siderosis), strokes, severe white matter disease (related to small vessel ischaemia)
• There were significant other neurological, psychiatric or medical conditions

Results of the TRAILBLAZER ALZ 2 trial:

• Doses were 700mg x 3, then 1400mg monthly
• All participants continued to decline, ie treatment did not stop decline
• Donanemab treated patients declined slightly slower (35% reduction for low tau burden patients and 22% reduction for combined tau burden patients, with modelling showing an "average" of 5 months less decline over the 18 months)
• On treatment, 6 monthly amyloid-PET scans showed return to normal levels of amyloid in 30% at 6 months, 70% at 12 months and 80% at 18 months.
• A marker of neurodegeneration (plasma ptau217) showed reduced tau production in the donanemab treated group (significant from 3 months onwards).
• Subgroups: Some groups did not show statistical benefit including patients with apolipoprotein E4 homozygosity, and if less than 65 years of age. These groups had smaller numbers of participants so it is not certain if they would individually respond to treatment. There is another TRAILBLAZER 5 study currently evaluating some of these groups, including patients of Asian background who were also underrepresented.

Adverse effects:

• ARIA stands for "amyloid related imaging abnormalities" which are either oedema (ARIA-E, reversible brain swelling) or haemorrhages (ARIA-H, typically small microbleeds in the cortex or outer layers of the brain, but also on the surface ['siderosis'] or within the lobes ("lobar")).
• ARIA is detectable using MRI (including special sequences sensitive to haemorrhage).
• MRIs are recommended for detecting ARIA at routine safety check points during the first year.
• ARIA also occurred in the placebo treated group (ARIA-E 2%, ARIA-H 14%) so is a part of Alzheimer disease in some people even without anti-amyloid antibody therapy.
• ARIA-H occurs in treated people also within areas of ARIA-E.
• ARIA usually (2/3) occurs without any symptoms and does not cause persisting impairment. The ARIA-E resolves, but the result of any haemorrhage (residual tissue iron deposits) remain permanently and are detected on MRI also.
• ARIA usually occurs in the first 3-6 months, and typically resolves within 2-4 months.
• Management depends on severity, and presence of symptoms. Most ARIA is without symptoms. Management can include continuing, postponing or stopping infusions, and sometimes medication (steroids) to reduce swelling.
• ARIA occurred in 37% of patients overall (ARIA-E 24%) but only 6% had symptoms
• ARIA occurred more in those with apolipoprotein E4/E4 status - 40% (non-carriers 15%)
• Mild symptoms: headache, confusion, nausea, dizziness
• Serious symptoms: focal "stroke-like" deficits, seizures, more marked brain impairment or death
• There were 3 deaths in this trial thought due to the drug causing ARIA, and one further death in a participant who was on placebo. For lecanemab, it is worth noting that there was 1 death of treated patient who suffered a stroke, and was given clot-busting therapy (tPA) leading to massive intracerebral haemorrhage.
• There have been deaths in the Open Label Extension as well which were not always thought related to drug but emphasizing that this is not a benign treatment (and patients are generally older so more prone to co-morbid conditions that might lead also to death).
• Infusion reactions occurred in only 9% of patients (self-limited allergic reactions, headache, fever, flu-like symptoms, nausea and vomiting).

Results of the TRAILBLAZER ALZ 6 Trial

This was a subsequent trial with more slowly escalating dosage regimen (ie 350mg increments to the final dose of 1400mg). It showed a lower incidence of ARIA (ARIA-E 14%) with a comparable amyloid clearance. This is the regimen we will be using at Epworth Freemasons.

Eligibility for this triage clinic

Potentially eligible if:

• Symptoms are caused by Alzheimer disease
• There is a "rapid forgetting" pattern of memory impairment, or isolated cognitive impairment syndromes caused by Alzheimer disease (eg primary progressive aphasia, posterior cortical atrophy, etc)
• There is mild cognitive impairment or mild dementia due to Alzheimer disease
• Age is < 90 years
• MMSE ≥ 20/30
• Patients are willing to pay for ApoE status test (~$200), donanemab (estimated to be $4700 per infusion = $56,400 per annum + GST), typically for 18 months, amyloid-PET scans are $2000 each and one 6 monthly (to determine whether therapy can be ceased due to amyloid levels returning to normal) and safety MRIs (3-4 per year). Please note that none of these are subsidized by Medicare or private health funds
• Patients have private health cover (to pay for hospital visits, infusions, IV sets, etc)
• Participants on treatment should consider wearing a Medi-Alert bracelet (or similar) all the time in case they have a heart attack or stroke needing urgent medical care (to avoid having clot-busting drugs). You will be given a card with treatment information on it for you to carry with you in case of stroke or heart attack.
• Patients have a reliable partner or support person to ensure attendance at visits and reporting of possible side effects.

NOT Eligible if:

• Are E4/E4 homozygotes
• Symptoms are caused by another brain disease (e.g. fronto-temporal dementia, Dementia with Lewy bodies, Parkinson's disease dementia, Alzheimer disease mimics, vascular dementia, etc)
• Laboratory studies have found a significant contributing condition (see below)
• MRI FLAIR sequences show severe small vessel ischaemic disease (Fazekas 3)
• MRI GRE/SWI sequences show 3 or more cortical microhaemorrhages, ≥ 1 area of superficial siderosis, prior lobar haemorrhage or ≥ 3 lacunar or cortical infarctions

Patients will be required to have the following done by their specialist/GP before their appointment and consideration of infusions:

• MMSE ≥ 20 (using serial subtraction, not reverse spelling)
• Laboratory studies: minimum U&E, Cr, LFTs, Ca, Mg, TSH, FBE, ESR, HbA1c, RPR, HIV, clotting profile
• MRI scan (3T): with 3D MPRAGE (or equivalent) with coronal reconstructions, axial FLAIR, axial GRE/SWI sequences minimum within 6 months of referral.
• FDG-PET scan: to show typical symptomatic Alzheimer disease regional changes. This is usually arranged by your specialist (neurologist, geriatrician, psychiatrist) but must include a NeuroStat quantitative analysis. This is in part Medicare subsidized.

• Preferred:
• Apolipoprotein E status testing: this is required to alert us to E4 status, which requires more intensive monitoring. We prefer this to be arranged by your specialist (eg via Dorevitch or Melbourne Pathology for about $154) since if homozygous E4E4, you would not be eligible.
• Amyloid-PET scan: within 2 years. This is required to show excess amyloid (private cost is $2000, but some patients will have had these done in trials, by ADNeT, or other means). This can be arranged by your specialist, or we can arrange if not yet done.

If considered to be eligible after your assessment, all infusions will be done at the Epworth Freemasons Day Unit (124 Grey St, East Melbourne VIC 3002).

Doses will use the TRAILBLAZER ALZ 6 dose escalation (TGA approved) of 350mg, 700mg, 1050mg, then maintenance 1400mg monthly (see Wang et al 2024) which reduces risk of ARIA.

Each vial contains 350mg and costs $1170 at present, with total cost over 18 months about $77,220.

A patient handout summarising this information is available here: Patient information brochure.

Request a new triage clinic appointment

MRIs will be done at the routine safety check points (typically after the 2,3,4 and 7 infusions).

Prescribing information (Australian recommendations for Kisunla) are available HERE.

If you consider the patient fulfills the above eligibility criteria, you can request an appointment by tapping the "Triage Booking Request Information" button below and filling in the form.

Please note also that all identifying personal information is encrypted in our database.

If you have already been seen at MCS by one of our specialists, please use the normal booking request form and include your request for a "triage assessment" please. You can use this link: Go to booking request page.

Triage Booking Request Information (tap to toggle open)

Select the details of your request below, and then click the submit button for verification of your request to this specialist.

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If you wish to Upload a zipped archive of a referral letter or other documents relevant to your appointment, please CLICK HERE. Otherwise, please bring these documents to your appointment.