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2024 AAAAI HAE Conference Coverage

CE / CME

Key Updates on Hereditary Angioedema: CCO Independent Conference Coverage of the 2024 AAAAI Annual Meeting

Physician Assistants/Physician Associates: 0.50 AAPA Category 1 CME credit

Nurses: 0.50 Nursing contact hour

Physicians: maximum of 0.50 AMA PRA Category 1 Credit™

Released: March 22, 2024

Expiration: March 21, 2025

Marc Riedl
Marc Riedl, MD, MS
CME/CE Information

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Donidalorsen for HAE: OLE of Phase II Trial

Donidalorsen, another agent being studied for long-term prophylaxis in HAE, is a subcutaneous (SC) 2′-O-methoxyethyl–modified antisense oligonucleotide that degrades mRNA in the liver. By reducing the translation and expression of plasma prekallikrein, donidalorsen reduces excessive bradykinin release, thereby preventing HAE attacks. The randomized phase II trial reported a 90% mean reduction in HAE attacks per month and fewer AEs compared with placebo.3

At AAAAI 2024, additional data were reported from the OLE study following the phase II CHARTER-1 trial. This study enrolled adults with type I or II HAE who completed the initial phase II trial through Week 17. In total, 17 patients were enrolled to receive SC donidalorsen 80 mg every 4 weeks for 13 weeks. If patients were attack free at Week 13, they were permitted to switch to SC donidalorsen 80 mg every 8 weeks based on the investigator’s judgement. Other fixed-dosing schedules included maintaining SC donidalorsen 80 mg every 4 weeks or switching to 100 mg every 4 weeks. This extension ended at Week 109.4,5

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Donidalorsen in HAE—OLE of Phase II Trial: 1 Year vs 2 Years

Efficacy results for this study compared Year 1 vs Year 2 data. Among the 17 patients enrolled on the OLE trial (Year 2), 14 completed ≥2 years of treatment.

Mean attack rate reduction was sustained through Year 2—94.6% at Year 1 and 96.0% at Year 2. Furthermore, donidalorsen improved angioedema-related quality of life in 86% of subjects at Year 1 and 100% at Year 2.

Additional data illustrate the impact of donidalorsen from Year 1 vs Year 2, respectively, on mean HAE attack-free days (99.6% vs 99.7%), percentage of attack-free patients for ≥6 months (82.4% vs 94.1%), and mean monthly attack rate needing acute therapy (0.05 vs 0.03). Therefore, there was durable efficacy data throughout 2 years of treatment with donidalorsen.

Regarding safety, there were no major concerns observed. Two patients reported injection-site reactions or skin discoloration at the injection site. Of importance, no serious AEs or TEAEs led to treatment discontinuation through the OLE study period.5

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Donidalorsen Q8W for HAE: Efficacy, AE-QoL, and Safety

Another poster at AAAAI 2024 presented details on the 8-week dosing schedule of SC donidalorsen 80 mg during the OLE study (Year 2). Eight patients were included in this cohort, with 5 patients continuing this dosing schedule to the end of the study.

SC donidalorsen 80 mg every 8 weeks decreased the overall attack rate by 82.9% over 2 years of treatment. This attack rate reduction was durable for those who maintained the 8-week dosing schedule, with an 83.6% reduction in the first year and 98.2% reduction in the second year compared with baseline. Of interest, most patients (6 of 8 in Year 1 and 5 of 6 in Year 2) were attack free after treatment with donidalorsen. Finally, investigators reported continued improvements in angioedema-related quality-of-life scores.

Regarding safety, there were no major concerns seen in this cohort. One patient reported abdominal pain that investigators report was possibly related to donidalorsen. No serious AEs or TEAEs that led to treatment discontinuation were observed over the 2 years of the study. Therefore, evidence suggests that 8-week dosing of donidalorsen is durably effective for some patients.4

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Donidalorsen: Summary

The collective data of donidalorsen illustrated significant reductions in attack rates during Years 1 and 2 of treatment for those who continued through the OLE study period. These findings correlated with clinically significant improvements in angioedema-related quality of life through Year 2. As noted, a cohort of patients on the 8-week 80-mg dosing schedule maintained an effective reduction in attack rates and improvement in quality of life. Finally, no serious AEs or TEAEs that led to treatment discontinuation were observed.

Overall, these abstracts provide reassuring efficacy and safety data for long-term prophylaxis with donidalorsen in patients with HAE.4,5

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