Aducanumab-avwa

Amyloid-plaques Model

What is Aducanumab-avwa?

It is the first drug for Alzheimers.

What are the uses of this medicine?

ADUHELM is indicated for the treatment of Alzheimer's disease. Treatment with ADUHELM should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with ADUHELM. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

Who Should Not Use this medicine?

Pregnant women and people who do not have Alzheimer's should not take this medication.

Is this medicine FDA approved?

Yes, Aducanumab-avwa is FDA approved.

What side effects can this medication cause?

The most common observed during clinical trials were brain swelling and tiny brain bleeds. Headaches, falls, diarrhea and confusion were also reported

Amyloid Related Imaging Abnormalities

ADUHELM can cause amyloid related imaging abnormalities-edema (ARIA-E), which can be observed on MRI as brain edema or sulcal effusions, and amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis.

Obtain recent (within one year) brain magnetic resonance imaging (MRI) prior to initiating treatment. The safety of ADUHELM in patients with any pre-treatment localized superficial siderosis, 10 or more brain microhemorrhages, and/or with a brain hemorrhage greater than 1 cm within one year of treatment initiation has not been established.

In clinical studies of ADUHELM, the severity of ARIA was classified by radiographic criteria, as shown in TABLE 2.

Table 2: ARIA MRI Classification Criteria

ARIA Type	Radiographic Severity
	Mild	Moderate	Severe
ARIA-E	FLAIR hyperintensity confined to sulcus and or cortex/subcortical white matter in one location < 5 cm	FLAIR hyperintensity 5 to 10 cm, or more than 1 site of involvement, each measuring < 10 cm	FLAIR hyperintensity measuring > 10 cm, often with significant subcortical white matter and/or sulcal involvement. One or more separate sites of involvement may be noted.
ARIA-H microhemorrhage	≤ 4 new incident microhemorrhages	5 to 9 new incident microhemorrhages	10 or more new incident microhemorrhages
ARIA-H superficial siderosis	1 focal area of superficial siderosis	2 focal areas of superficial siderosis	> 2 focal areas of superficial siderosis

In Studies 1 and 2, ARIA (-E and/or -H) was observed in 41% of patients treated with ADUHELM with a planned dose of 10 mg/kg (454 out of 1105), compared to 10% of patients on placebo (111 out of 1087).

ARIA-E was observed in 35% of patients treated with ADUHELM 10 mg/kg, compared to 3% of patients on placebo. The incidence of ARIA-E was higher in apolipoprotein E ε4 (ApoE ε4) carriers than in ApoE ε4 non-carriers (42% and 20%, respectively). The majority of ARIA-E radiographic events occurred early in treatment (within the first 8 doses), although ARIA can occur at any time. Among patients treated with a planned dose of ADUHELM 10 mg/kg who had ARIA-E, the maximum radiographic severity was mild in 30%, moderate in 58%, and severe in 13% of patients. Resolution occurred in 68% of ARIA-E patients by 12 weeks, 91% by 20 weeks, and 98% overall after detection. 10% of all patients who received ADUHELM 10 mg/kg had more than one episode of ARIA-E.

ARIA-H in the setting of ARIA-E associated with the use of ADUHELM 10 mg/kg was observed in 21% of patients treated with ADUHELM 10 mg/kg, compared to 1% of patients on placebo. There was no imbalance in isolated ARIA-H (i.e., ARIA-H in patients who did not also experience ARIA-E) between ADUHELM and placebo. There was no imbalance in hemorrhage greater than 1 cm between ADUHELM and placebo.

Clinical symptoms were present in 24% of patients treated with ADUHELM 10 mg/kg who had an observation of ARIA (-E and/or -H), compared to 5% of patients on placebo. The most common symptom in patients treated with ADUHELM 10 mg/kg with ARIA was headache (13%). Other frequent symptoms were confusion/delirium/altered mental status/disorientation (5%), dizziness/vertigo (4%), visual disturbance (2%), and nausea (2%). Serious symptoms associated with ARIA were reported in 0.3% of patients treated with ADUHELM 10 mg/kg. Clinical symptoms resolved in the majority of patients (88%) during the period of observation.

Enhanced clinical vigilance for ARIA is recommended during the first 8 doses of treatment with ADUHELM, particularly during titration, as this is the time the majority of ARIA was observed in Studies 1 and 2. If a patient experiences symptoms which could be suggestive of ARIA, clinical evaluation should be performed, including MRI testing if indicated. If ARIA is observed on MRI in the presence of clinical symptoms, careful clinical evaluation should be performed prior to continuing treatment.

Obtain brain MRIs prior to the 7^th infusion (first dose of 10 mg/kg) and 12^th infusion (sixth dose of 10 mg/kg) of ADUHELM to evaluate for the presence of asymptomatic ARIA. For patients with radiographic findings of ARIA, enhanced clinical vigilance is recommended. Additional MRIs may be considered if clinically indicated. If radiographically severe ARIA-H is observed, treatment may be continued with caution only after a clinical evaluation and a follow-up MRI demonstrates radiographic stabilization (i.e., no increase in size or number of ARIA-H). For ARIA-E or mild/moderate ARIA-H, treatment may continue with caution. If dosing is temporarily suspended, dosing may resume at that same dose and titration schedule. There are no systematic data on continued dosing with ADUHELM following detection of radiographically moderate or severe ARIA. In Studies 1 and 2, temporary dose suspension was required for radiographically moderate or severe ARIA-E and radiographically moderate ARIA-H. In Studies 1 and 2, permanent discontinuation of dosing was required for radiographically severe ARIA-H. The benefits of reaching and maintaining the 10 mg/kg dose should be considered when evaluating a potential dose suspension.

5.2 Hypersensitivity Reactions

Angioedema and urticaria were reported in one patient in the placebo-controlled period of Studies 1 and 2, and occurred during the ADUHELM infusion. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction, and initiate appropriate therapy.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Pregnancy

Risk Summary

• There are no adequate data on ADUHELM use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
• In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
• The background risk of major birth defects and miscarriage for the indicated population is unknown.

Can this medicine be used in children?

It should not be used on children

How Supplied

• ADUHELM (aducanumab-avwa) injection is a preservative-free, sterile, clear to opalescent, and colorless to yellow solution. ADUHELM is supplied one vial per carton as follows:
• 170 mg/1.7 mL (100 mg/mL) single-dose vial (with red flip cap) – NDC 64406-101-01
• 300 mg/3 mL (100 mg/mL) single-dose vial (with blue flip cap) – NDC 64406-102-02

Storage and Handling

Unopened Vial

• Store in original carton until use to protect from light.
• Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Do not freeze or shake.
• If no refrigeration is available, ADUHELM may be stored unopened in its original carton to protect from light at room temperature up to 25°C (77°F) for up to 3 days.
• Prior to dilution, unopened vials of ADUHELM may be removed from and returned to the refrigerator if necessary, when kept in the original carton. Total combined time out of refrigeration with protection from light should not exceed 24 hours at room temperature up to 25°C (77°F).

• Dailymed label info on Aducanumab-avwa
• FDA Aducanumab-avwa

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