Garadacimab provides early protection against HAE attacks

Subcutaneous prophylactic treatment with garadacimab significantly reduced the monthly number of attacks and led to attack-free status as early as week 1 in patients with hereditary angioedema (HAE) in the post hoc analysis of the phase III VANGUARD study presented at ACAAI 2023.

Patients treated with garadacimab had a substantial reduction in HAE attacks compared with those treated with placebo as early as week 1 (0.11 vs 1.81) and was sustained through week 6 (0.27 vs 2.01). [ACAAI 2023, abstract P051]

As a result, the secondary endpoint of mean monthly HAE attack rate was significantly decreased by 87 percent (p<0.0001) with garadacimab at month 6.

The researchers analysed 64 patients aged ≥12 years with HAE who had ≥1 attack per month. After the run-in period of 1–2 months, participants were randomly assigned to receive subcutaneous garadacimab at an initial dose of 400 mg, followed by a dose of 200 mg once monthly for 6 months (n=39) or a placebo (n=25).

There was a substantial reduction in HAE attacks with garadacimab at week 1 compared to the run-in period (0.11 vs 3.07). Garadacimab consistently reduced the mean monthly number of attacks over the 6-month study period, said Dr Raffi Tachdjian from David Geffen School of Medicine at the University of California Los Angeles, California, US.

In addition, the garadacimab group had a greater probability of being attack-free at week 1 than did the placebo group, with rates ranging from 97.4 to 92.3 percent with garadacimab vs 66.7 to 50 percent with placebo. The difference in attack-free status has been consistently observed with garadacimab throughout the study period, according to Tachdjian.

Overall, the findings suggest that the first injection of garadacimab provided early protection against HAE attacks within the first week of treatment, resulting in a substantial reduction in the mean monthly HAE attack rate that was sustained through the entire 6-month treatment period, said Tachdjian.

Additionally, patients treated with garadacimab remained attack-free for a longer period than those treated with placebo, an effect that was also observed as early as week 1, he added.

Long-term quality of life

In terms of quality of life (QoL), a lower AE-QoL* total score, indicating a better QoL, was observed in the garadacimab group vs the placebo group at month 6 (11.7 vs 40.3; mean change from baseline -26.5 vs -2.2), and this result was sustained through month 12 in the open-label extension (OLE) study. [ACAAI 2023, abstract P084]

“Clinically meaningful and long-term improvements in QoL and patient-reported outcomes were associated with garadacimab in both the pivotal phase III VANGUARD and ongoing OLE studies, consistent with the durable efficacy observed,” said the researchers.

“Overall, there was a positive, long-term impact to garadacimab prophylaxis in HAE patients,” they added.