- Jul 14, 2023
- 2 min read

Finally... Therapeutics that slow Alzheimer’s

Updated: Aug 16, 2023

But, which is the best?

• Some anti-beta amyloids (ABs) made it

⇒ thru pos Ph3

⇒ 1 full FDA approval

But lots of ABs have died in clinical trials!

• gantenerumab, bapineuzumab, solanezumab, etc.

⇒ Benefit vs. Risk = Efficacy vs. ARIA (brain swelling)

⇒ Precise binding props (& more?) are important 🫶

See comparison image (thx ABOS)

For those ABs that made it thru Ph3… which is best?

Lecanemab (Leqembi)

• Full FDA approval

• Eisai et al.

• Binding props:

⇒ Strongest: protofibrils

⇒ Some binding: oligomers & insoluble fibrils

• Symptomatic ARIA: 4%

• Efficacy*: -27%

• Commercial success?

Aducanumab (Aduhelm)

• Conditional FDA approval

• Eisai et al.

• Binding props:

⇒ Strongest: amyloid plaque

⇒ Other binding: protofibrils

• Symptomatic ARIA: 10-29%

• Efficacy*: -22%, +2%, -27%**

• Commercial & PR disaster!

Donanemab

• BLA filed?

⇒ Will confirm at #AAIC investor call next week?

• LLY

• Binding props:

⇒ Strongest: amyloid plaque

⇒ Other binding: None?

• Symptomatic ARIA: 6%

• Efficacy*: -36%

• Pre-commercial

⇒ Pos Phase 3

⇒ Will FDA approve full BLA?

Caution:

The table comparing ARIA and efficacy across Leqembi, Aduhelm, and donanemab is a cross-trial comparison.

There is some side-by-side data from LLY of donanemab and Aduhelm.

Brain amyloid plaque clearance @ 6 months:

37.9% for donanemab

1.6% for Aduhelm

ARIA comparison @ 6 months

Aduhelm: total ARIA = 26.1% ; Symptomatic = 4.3%

Donanemab: total ARIA = 25.4%; Sympt = 2.8%

all symptomatic was ARIA-E