Kisunla (Donanemab-azbt) Comparison to Other Alzheimer Treatments

Donanemab-azbt (Kisunla) demonstrates distinct advantages and trade-offs compared to other Alzheimer's treatments, particularly monoclonal antibody therapies like lecanemab and aducanumab. Here's a structured comparison:

Mechanism of Action

Donanemab: Targets mature, aggregated amyloid-beta plaques (N-terminal pyroglutamate Aβ).
Lecanemab: Binds soluble Aβ protofibrils earlier in plaque formation.
Aducanumab: Recognizes both fibrillar and soluble Aβ aggregates.

Cognitive & Functional Efficacy

Treatment	Cognitive Decline Reduction (vs placebo)	Key Trial Findings
Donanemab	35% (low/medium tau group)	39% lower disease progression risk; 47% halted progression at 1 year
Lecanemab	27% (ADAS-Cog)	Slower decline in daily living scores vs donanemab
Aducanumab	22% (ADAS-Cog)	Less effective than donanemab/lecanemab in network meta-analyses

Donanemab showed 3× greater effect size than lecanemab/aducanumab on the Clinical Dementia Rating scale (CDR-SB) in head-to-head analyses.

Amyloid Clearance

Speed: Donanemab clears plaques faster (84% reduction at 18 months vs lecanemab’s 59% at 18 months).
Dosing Protocol:
- Donanemab: Monthly infusions with potential treatment cessation upon plaque clearance
- Lecanemab: Biweekly indefinite infusions

Safety Profile

Adverse Event	Donanemab	Lecanemab	Aducanumab
ARIA-Edema (ARIA-E)	24%[1]	12.6%[3]	35%[4]
Microhemorrhages	25%[1]	17%[3]	19%[4]
Treatment-related deaths	0.3%[1]	0.7%[3]	0.4%[4]

Donanemab has higher ARIA risk than lecanemab but lower mortality risk[1][3]. All three antibodies show worse tolerability than placebo.

Practical Considerations

Patient Selection:

Donanemab works best in low/medium tau populations (no significant effect in high tau)
Requires APOE ε4 testing due to ARIA risk stratification

Monitoring Burden:

Donanemab: Frequent MRIs (5 scans in first 7 months)
Lecanemab: Less intensive monitoring but lifelong dosing

Cost/Workflow:

Donanemab’s potential finite treatment duration (6-18 months) may reduce long-term costs
Both require specialized infusion centers

Emerging Comparisons

Lithium: Outperformed donanemab on MMSE in meta-analyses but lacks large-scale AD validation.
Combination Therapies: Research ongoing with tau-targeting drugs to address donanemab’s limited efficacy in high-tau patients.

Donanemab offers a time-limited treatment option with strong cognitive benefits for early AD patients, but requires careful risk-benefit analysis due to monitoring demands and ARIA risks. Lecanemab may be preferable for patients needing lower ARIA risk tolerance, while aducanumab lags in efficacy comparisons.