Hereditary angioedema controlled in 4 weeks with deucrictibant
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Key takeaways:
- Deucrictibant is an orally administered bradykinin B2 receptor antagonist.
- 90% of the treatment groups achieved control by 12 weeks.
- Quality of life scores improved by 25.9 points at 12 weeks.
BOSTON — Patients with hereditary angioedema who used deucrictibant for 12 weeks experienced improved symptom control, according to a poster presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.
Patients also saw improved health-related quality of life and treatment satisfaction, Peng Lu, MD, PhD, chief medical officer, Pharvaris, and colleagues wrote.
Most prophylactic and on-demand treatments for hereditary angioedema (HAE) attacks are administered via intravenous or subcutaneous injection, Lu told Healio, with only one oral therapy approved for HAE attack prevention.
“Deucrictibant, an investigational, oral bradykinin B2 receptor antagonist, aims to offer injectable-like efficacy and placebo-like tolerability with the convenience of an oral therapy,” Lu said.
“By potentially bringing the promise of both a prophylactic and on-demand treatment options to people living with HAE, Pharvaris aims to enable those with HAE to have fewer minimal disruptions in their daily activities, resulting in an improved quality of life,” Lu continued.
The two-part, phase 2 CHAPTER-1 study enrolled 34 patients aged 18 to 75 years with type 1 or 2 HAE. They were not receiving any other prophylactic treatments when they were screened, but they had experienced three or more attacks within the previous 3 months or two or more attacks during the 8 weeks of the screening period.
Patients received 20 mg or 40 mg of deucrictibant or placebo each day for 12 weeks. The deucrictibant doses were delivered as pairs of 10 mg or 20 mg immediate-release capsules.
Mean Angioedema Control Test (AECT) scores at baseline included 7.1 for the placebo group (n = 8), 8.1 for the 40 mg group (n = 10) and 9.2 for the 20 mg group (n = 10).
At week 4, mean AECT scores included 9.4 for the placebo group and 13.9 for both the 20 mg and 40 mg groups. The mean AECT scores for week 8 included 10.8 for the placebo group, 14 for the 20 mg group and 14.7 for the 40 mg group. The week 12 scores included 8.4 for the placebo group, 14.1 for the 40 mg group and 14.2 for the 20 mg group.
Overall, 18.2% of 11 patients in the placebo group reported well-controlled HAE based on their AECT score at baseline. At week 12, 37.5% of eight patients in the placebo group reported well-controlled HAE.
In the treatment groups, 70% of 10 patients in the 20 mg deucrictibant group and 33.3% of 12 patients in the 40 mg group reported well-controlled HAE. These proportions increased to 90% of 10 patients for both the 20 mg and 40 mg groups at week 12.
Angioedema Quality of Life (AE-QoL) Questionnaire scores improved for eight patients in the placebo group by means of 7.4 points at week 4, 10.9 points at week 8 and 11.9 points at week 12.
In the 20 mg group, AE-QoL Questionnaire scores improved for 10 patients by means of 15.1 points at week 4, 20.4 points at week 8 and 19 points at week 12.
The scores for the 40 mg group improved for 10 patients by means of 21.1 points at week 4, 22.7 points at week 8 and 25.9 points at week 12.
The “fear/shame” and “functioning” domains had the greatest improvements in the treatment groups.
Effectiveness scores in the Treatment Satisfaction Questionnaire for Medication (TSQM) Version II tool included 50 for the placebo group, 90 for the 20 mg group and 86.7 for the 40 mg group.
Similarly, side effect scores in the TSQM tool included 100 for the placebo and 20 mg groups and 98.3 for the 40 mg group. Convenience scores included 70.8 for the placebo group, 80 for the 20 mg group and 73.9 for the 40 mg group.
Finally, global satisfaction scores included 59.4 for the placebo group, 89.2 for the 20 mg group and 85.8 for the 40 mg group.
Previously announced results from the CHAPTER-1 study indicated that the 40 mg doses were safe and well tolerated, with no serious or severe treatment-emergent adverse events and no adverse events that led to study discontinuation or withdrawal.
Based on these findings, the researchers concluded that deucrictibant improved control and health-related quality of life for patients with HAE while providing treatment satisfaction, with results as early as 4 weeks and improving through 12 weeks.
“The CHAPTER-1 phase 2 trial provides encouraging results on the effects of prophylactic treatment with oral deucrictibant for 12 weeks on HAE disease control, health-related quality of life, including both function and mental, and treatment satisfaction in people living with HAE,” Lu said.
Lu also called the rapid and sustained improvements in disease control and health-related quality of life (HRQoL), which occurred as early as week 4, significant and demonstrative of the fast onset effects of deucrictibant.
“Deucrictibant treatment resulted in much greater patient satisfaction with effectiveness and greater overall patient satisfaction vs. placebo, suggesting deucrictibant has the potential to meet current unmet needs in the treatment landscape,” Lu said.
“Deucrictibant not only provides strong disease control but also significantly improves the quality of life of those living with HAE, making it an important consideration for future prophylactic treatment plans,” Lu continued. “This is significant given people with HAE currently still have a need for more convenient treatment options without sacrificing efficacy and safety.” The researchers plan on presenting data showing maintained improvements in disease control and quality of life through a year of treatment with deucrictibant at upcoming scientific conferences as their studies continue.
“Confirmation of these phase 2 data in the planned phase 3 pivotal study may provide further evidence of deucrictibant as a potential best-in-class treatment to address existing unmet needs in HAE disease control and HRQoL,” Lu said.
Pharvaris is now enrolling patients in its RAPIDe-3 trial and expects to initiate CHAPTER-3 by the end of 2024.
“Data from those studies will inform submission timelines to the FDA in the coming years,” Lu said.