Approval of Aducanumab for Alzheimer Disease—The FDA’s Perspective

The FDA granted accelerated approval to aducanumab and stated that reduction of amyloid is reasonably likely to predict clinical benefit.

“The FDA has controversially granted accelerated approval to aducanumab and has opined that the reduction of amyloid is reasonably likely to predict clinical benefit 7,9,[98][99][100][101][102][103][104][105][106][107] .”

Aducanumab was given FDA approval under the expedited approval pathway to treat moderate AD.

“Aducanumab has been given FDA approval under the expedited approval pathway to treat moderate AD [134,135,136].”

Lecanemab is a humanized IgG1 monoclonal antibody specifically targeting aggregated forms of amyloid beta and was given fast approval by the FDA.

“Lecanemab (LEQEMBI, brand name), a different monoclonal antibody known as humanized immunoglobulin G1 (IgG1), which specifically targets aggregated forms of amyloid beta, was also given fast approval by the FDA earlier in the year [134,135,136].”

Reduction in amyloid-beta brain plaques and encouraging clinical outcomes in one of two pivotal Phase III trials were factors cited for aducanumab's expedited approval.

“The reduction in amyloid-beta brain plaques, a purported surrogate endpoint that indicates the “progression” of AD, and the encouraging clinical outcomes in one of the two pivotal Phase III trials were two of the factors cited for aducanumab’s expedited approval [130,134,135,136].”

Both EMERGE and ENGAGE trials presented evidence of an intermediate effect of aducanumab on biomarkers, indicating amyloid removal, which is likely linked to the clinical benefit of aducanumab.

“Both trials presented evidence of an intermediate effect of the drug on biomarkers, indicating amyloid removal, which is likely linked to the clinical benefit of aducanumab.”

In the EMERGE trial, the findings reached statistical significance.

“However, the findings of the EMERGE trial reached statistical significance, whereas the primary endpoint was not reached in the ENGAGE trial.”

In the ENGAGE trial, the primary endpoint was not reached.

“However, the findings of the EMERGE trial reached statistical significance, whereas the primary endpoint was not reached in the ENGAGE trial.”

An exploratory analysis revealed that a subgroup of participants in the ENGAGE trial who received a high dose of aducanumab exhibited slow decline similar to that observed in the EMERGE trial.

“An exploratory analysis revealed that a subgroup of the participants in the ENGAGE trial who received a high dose of aducanumab exhibited slow decline, which was similar to that observed among the participants in the EMERGE trial.”

Aducanumab, a monoclonal antibody against Aβ aggregates, obtained FDA approval as an Alzheimer's drug for its ability to reduce the level of Aβ plaques in patients with early AD or MCI.

“Aducanumab, a monoclonal antibody against Aβ aggregates, has obtained the FDA’s approval as an Alzheimer’s drug for its ability to reduce the level of Aβ plaques in patients with early AD or mild cognitive impairment (MCI).46–48”

Two antibody-based drugs, aducanumab and lecanemab, have been approved by the FDA.

“So far, two antibody-based drugs aducanumab and lecanemab have been approved by the FDA”

Aducanumab is the first FDA-approved therapy for Alzheimer's.

“Aducanumab is the first FDA-approved therapy for Alzheimer’s.47,48”