# Donidalorsen for Long-Term Prophylaxis of Hereditary Angioedema Attacks: Results from the OASISplus Open-Label Extension Cohort at Year 1.

- **DOI:** [10.2147/jaa.s592079](https://doi.org/10.2147/jaa.s592079)
- **Rating:** Sound (3.6 out of 5)
- **Verdict:** One-year extension data strengthen donidalorsen’s durability and safety case, but the uncontrolled rollover design limits independent efficacy inference.
- **Framework version:** v5.9
- **Pipeline version:** v0.4
- **Evaluation date:** 2026-09-18
- **Evaluation page:** https://www.nabu.science/paper/10.2147%2Fjaa.s592079

## Key claims

1. From Weeks 0 to 52, reductions in mean HAE attack rate from OASIS-HAE baseline were 94% (Q4W) and 95% (Q8W)
   - Support: Supported
   - Type: Primary finding
   - Basis: large descriptive reductions in an uncontrolled rollover cohort without a concurrent comparator
   - Location: Abstract, Results; Results, Efficacy
2. Donidalorsen demonstrated sustained reductions in HAE attack rate, improvements in QoL, and an acceptable safety profile after 1 year of treatment.
   - Support: Supported
   - Type: Secondary
   - Basis: consistent one-year outcomes, though the open-label design limits independent efficacy attribution
   - Location: Abstract, Conclusion
3. patients reported clinically meaningful improvements in mean AE-QoL total score at Week 52 (Q4W, 28.1 points; Q8W, 26.7 points)
   - Support: Supported
   - Type: Secondary
   - Basis: validated scores exceeded the clinical threshold, but the uncontrolled comparison limits attribution
   - Location: Abstract, Results; Results, QoL, Disease Control, and Treatment Satisfaction
4. Twenty-two (27%) patients reported treatment-related TEAEs; none were serious, and injection-site reactions were the most frequently reported.
   - Support: Well-supported
   - Type: Secondary
   - Basis: directly documented adverse-event counts and classifications in the full treated cohort
   - Location: Abstract, Results; Results, Safety; Table 2

## Strengths

- **Detailed one-year safety characterization** Table 2 reports adverse-event incidence, seriousness, severity, treatment relationship, and discontinuations, while the Safety section provides narratives for serious events and laboratory abnormalities.
  - Dimension: methodological rigour
  - Location: Results, Safety; Table 2
- **Clinically relevant durability evidence** The study extends follow-up beyond the parent trial and reports attack rates, quality of life, disease control, treatment satisfaction, and median exposure through Year 1.
  - Dimension: contribution
  - Location: Results, Efficacy; Results, QoL, Disease Control, and Treatment Satisfaction
- **Limitations tied to interpretation** The Discussion identifies selection bias, racial homogeneity, the small Q8W subgroup, and the absence of a placebo comparator, including their implications for inference and generalisability.
  - Dimension: positioning
  - Location: Discussion, Limitations

## Limitations

- **No concurrent efficacy comparator** All Year-1 analyses are descriptive within an open-label rollover cohort, so the extension cannot independently separate treatment effects from selection, carryover, or temporal influences.
  - Dimension: methodological rigour
  - Location: Materials and Methods, Statistical Analysis; Discussion, Limitations
- **Sparse evidence for Q8W dosing** Only 14 participants received Q8W dosing, and eligibility for that schedule favored patients without recent breakthrough attacks, limiting regimen-specific conclusions.
  - Dimension: contribution
  - Location: Results, Patients; Table 1; Discussion, paragraph 2 and Limitations
- **Limited demographic transferability** The cohort was 91.6% White and included only seven adolescents, restricting confidence across racial, ethnic, and age subgroups.
  - Dimension: application pathway
  - Location: Table 1; Discussion, Limitations

## Reliability checks

Caveats (4 of 4 checks).

- **Internal coherence:** Clean. Participant disposition, exposure, efficacy denominators, and adverse-event totals reconcile across the abstract, Results, and Tables 1–2. The descriptive analysis matches the stated uncontrolled open-label design.
- **Research conduct:** Noted. Ethics approval and trial registration are declared, and the Data Availability Statement specifies conditions for access through Vivli. No conflict-of-interest disclosure statement appears in the supplied full text.
- **Reference integrity:** Clean. 22 of 22 checkable references verified
  - 28 references in manuscript
  - 6 are books, websites or datasets — counted, but not index-checkable
  - References not verified automatically are resolved manually within 24 hours.

## Post-publication record

- **Status:** Clean
- **Summary:** No retraction or expression of concern found in Crossref (includes Retraction Watch).
- **Last checked:** 2026-10-17