BRIEF SUMMARY

ADUCANUMAB- (June 2021)

Indn-  For treatment of Alzheimerr's disease  

Comp-  Injection: • 170 mg/1.7 mL (100 mg/mL) solution in a single-dose vial

 • 300 mg/3 mL (100 mg/mL) solution in a single-dose vial  The recommended maintenance dosage is 10 mg/kg administered as an intravenous infusion over approximately one hour every four weeks.

ADR-  Most common adverse reactions and higher incidence compared to placebo): ARIA-Edema, headache, ARIA-H microhemorrhage, ARIA-H superficial siderosis, and fall

Pat Inform-

Amyloid Related Imaging Abnormalities-                                                               Inform patients that may cause Amyloid Related Imaging Abnormalities or “ARIA”. ARIA most commonly presents as 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, or nausea.

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U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 27

Name of the Drug-    ADUHELM

Active Ingredient -   Aducanumab

Pharmacological Classification-    For treatment of Alzheimerr's disease                                                                                                                                                                   Date of Approval-          6/7/2021                      

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                             ADUHELM™ safely and effectively.

See full prescribing information for ADUHELM. ADUHELM™ (aducanumab-avwa) injection, for intravenous use

Initial U.S. Approval: 2021

INDICATIONS AND USAGE-

 ADUHELM is an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease.

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).

ADVERSE REACTIONS-

 Most common adverse reactions (at least 10% and higher incidence compared to placebo): ARIA-Edema, headache, ARIA-H microhemorrhage, ARIA-H superficial siderosis, and fall. 

 CONTRAINDICATIONS-

 None.

WARNINGS AND PRECAUTIONS-

 • Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 8 doses of treatment with ADUHELM, particularly during titration. If a patient experiences symptoms which could be suggestive of ARIA, clinical evaluation should be performed, including MRI testing if indicated.

 • Hypersensitivity Reactions: Angioedema and urticaria have occurred. If a hypersensitivity reaction occurs, promptly discontinue the infusion of ADUHELM and initiate appropriate therapy.

DOSAGE AND ADMINISTRATION-

 • Titration is required for treatment initiation. 

 • The recommended maintenance dosage is 10 mg/kg administered as an intravenous infusion over approximately one hour every four weeks.

 • Obtain a recent (within one year) brain MRI prior to initiating treatment.

 • Obtain MRIs prior to the 7th and 12th infusions. If radiographic 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).

 • Dilution in 100 mL of 0.9% Sodium Chloride Injection, USP, is required prior to administration.

 • Administer as an intravenous infusion over approximately one hour via a 0.2 or 0.22 micron in-line filter. 

DOSAGE FORMS AND STRENGTHS

 Injection: • 170 mg/1.7 mL (100 mg/mL) solution in a single-dose vial

 • 300 mg/3 mL (100 mg/mL) solution in a single-dose vial

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 ADUHELM may cause Amyloid Related Imaging Abnormalities or “ARIA”. ARIA most commonly presents as 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, or nausea. Instruct patients to notify their healthcare provider if these  symptoms occur.

Notify patients that their healthcare provider will perform MRI scans to monitor for ARIA

Hypersensitivity Reactions-                                                                                        Inform patients that ADUHELM may cause hypersensitivity reactions, including angioedema and urticaria, and to contact their healthcare provider if hypersensitivity reactions occur 

Manufactured by: Biogen Inc. Cambridge, MA 02142 US License #1697 ADUHELM is a trademark of Biogen. © 2021 Biogen and Eisai

 CLINICAL PHARMACOLOGY -

1. Mechanism of Action-                                                                                           Aducanumab-avwa is a human, immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.

The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease. 

Pharmacodynamics- Effect of ADUHELM on Amyloid Beta Pathology ADUHELM reduced amyloid beta plaque in a dose- and time-dependent manner, compared with placebo.

3. Pharmacokinetics -The pharmacokinetics (PK) of ADUHELM were characterized using a population PK analysis with concentration data collected from 2961 subjects with Alzheimer’s disease who received ADUHELM in single or multiple doses.

Steady-state concentrations of ADUHELM were reached by 16 weeks of repeated dosing with an every 4-week regimen, and the systemic accumulation was 1.7-fold. The peak concentration (Cmax), trough concentration (Cmin), and area under the plasma concentration versus time curve at steady state (AUCss) of ADUHELM increased dose proportionally in the dose range of 1 to 10 mg/kg every 4 weeks

Distribution- The mean value (95% CI) for volume of distribution at steady state is 9.63 L (9.48, 9.79).

Elimination- ADUHELM is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. ADUHELM clearance (95% CI) is 0.0159 (0.0156, 0.0161) L/hr. The terminal half-life is 24.8 (14.8, 37.9) days.

4.Specific Populations- Body weight, age, sex, and race were found to impact exposure to ADUHELM. However, none of these covariates were found to be clinically significant.

Patients with Renal or Hepatic Impairment No studies were conducted to evaluate the pharmacokinetics of ADHUELM in patients with renal or hepatic impairment. ADUHELM is not expected to undergo renal elimination or metabolism by hepatic enzymes.

 USE IN SPECIFIC POPULATIONS-

1. Pregnancy Risk Summary There are no adequate data on ADUHELM use in pregnant women to evaluate for a drugassociated 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.

2. Lactation Risk Summary-                                                                                              There are no data on the presence of aducanumab-avwa in human milk, the effects on the breastfed infant, or the effects of the drug on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ADUHELM and any potential adverse effects on the breastfed infant from ADUHELM or from the underlying maternal condition.

3. Pediatric Use-                                                                                                               Safety and effectiveness in pediatric patients have not been established.

4. Geriatric Use-                                                                                                                In Studies 1 and 2, the age of patients ranged from 50 to 85 years, with a mean age of 70 years; 79% were 65 and older, and 32% were 75 and older. There were no notable differences in the incidence of adverse reactions between these age groups, and no additional safety concerns in patients 65 years of age and older compared to younger patients.