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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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Multistudy Program Evaluating Anti-FXIIa mAb Garadacimab as Long-term Prophylaxis for HAE Attacks

Next, I discuss SC garadacimab—a monoclonal antibody (mAb) targeting activated factor XII (FXIIa)—which is being studied for long-term prophylactic therapy in patients with HAE due to C1-INH deficiency (HAE-C1-INH). Of importance, FXIIa initiates the contact activation system and kallikrein-kinin pathway, resulting in bradykinin overproduction in this patient population because of an unregulated pathway.6

Researchers’ presentation at AAAI 2024 integrated garadacimab data from its phase II, pivotal phase III, and OLE trials. This is a unique way to look at the collective data to assess efficacy and safety of SC garadacimab monthly to prevent HAE attacks.

Patients aged 12 years or older with type I or II HAE and ≥1 attack per month were enrolled on each study (N = 205). The phase II trial evaluated various dosing schedules of SC garadacimab vs placebo, with 35 patients later enrolling on the phase III OLE trial. Then, the pivotal phase III evaluated SC garadacimab 200 mg monthly vs placebo, with 26 patients later enrolling on the phase III OLE trial. Finally, 69 new patients were enrolled on the phase III OLE trial that evaluated long-term prophylaxis with SC garadacimab with an initial loading dose and then 200 mg monthly for ≥12 months.

Based on specific inclusion criteria, there was some heterogeneity among included patients in this analysis. Patients from the phase II and pivotal phase III placebo groups were also included in this analysis (NCT04739059).7

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Garadacimab Multistudy Program: Baseline Characteristics

Looking at baseline characteristics of this integrated analysis, most patients received garadacimab (n = 172) vs placebo (n = 33). There was a slight predominance of females, and most patients were White and had type I HAE. Six patients (3%) had HAE with normal C1 inhibitor (HAE nC1-INH) confirmed by genetic testing.

The median exposure to treatment was 1.3 years vs 0.5 years for garadacimab vs placebo, respectively. Furthermore, 83.1% of patients were exposed to garadacimab for ≥1 year; 19.2% were exposed to garadacimab for ≥2 years.7

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Garadacimab Efficacy: Mean Monthly Attack Rate Reduction

Whereas placebo resulted in very little change in mean monthly attack rate, garadacimab resulted in an overall 94% reduction compared with the run-in period. These data show strong efficacy results that are consistent with each individual study, particularly the pivotal phase III trial.6-8

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Garadacimab Efficacy: Time to First HAE Attack

In evaluating efficacy, HAE prophylaxis with garadacimab resulted in a median time to first attack >1.9 years vs 0.03 years (or 11 days) with placebo. As seen in this analysis, <50% of patients had an attack at time of data cutoff. Therefore, the median time to first attack is beyond 1.9 years.7

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Garadacimab Efficacy for Long-term Prophylaxis in HAE

During a median garadacimab exposure of 1.2 years, 97% of patients had ≥50% reduction in attacks, 83% had ≥90% reduction in attacks, and 57% were 100% attack free compared with run-in.

A median 1.1 years was the longest duration that patients being treated with garadacimab were attack free vs a median 0.1 years for the placebo group. So there is a significant difference in median attack-free durations in this data set.7

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Garadacimab Safety With Long-term Prophylaxis in HAE

Evaluating the safety of a novel agent is always important. Looking across these studies of garadacimab, 86% of patients had ≥1 TEAE, but only 23% of those were identified to be related to garadacimab. Furthermore, most observed TEAEs (60% to 70%) were mild or moderate. No serious AE assessed as related to treatment was observed.

For AEs reported in ≥5% of patients, most AEs associated with garadacimab were injection-site reactions, in particular erythema. Rare reports of moderate swelling or irritation were observed. Only 1 TEAE led to study discontinuation, which was an injection-site reaction. Finally, 4% of patients experienced headaches that were potentially treatment related. No new or serious safety signals were reported.7

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Garadacimab Multistudy Program: Summary

In this multistudy data set of the garadacimab clinical program, efficacy data were high across all phases and OLE. HAE attacks were reduced by 94% vs run-in. This efficacy was maintained during a median of 1.2 years of treatment, and 57% of patients remained attack free during this time.

There were no reported significant safety concerns and no serious TEAEs; only 1 TEAE (injection-site reaction) led to discontinuation. Therefore, this large data set is helpful in evaluating the efficacy and safety of garadacimab for long-term prophylactic treatment of HAE.7

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Based on data presented at AAAAI 2024 by Craig and colleagues, which of the following outcomes would you describe to a patient considering using garadacimab if approved by the FDA for long-term prophylaxis of HAE attacks?

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