Persistent Symptom Control with s.c. Supplementation of C1 Inhibitor in Prophylactic Treatment of HAE

HAE Therapy Options

Hereditary angioedema due to C1 inhibitor (C1-INH) deficiency is a rare genetic disorder characterized by episodes of swelling in the face, limbs, trunk, and submucosal tissues of the gastrointestinal, genitourinary, or respiratory tracts. The attacks are painful and can be fatal if the upper respiratory tract is affected.

Treatment involves managing acute attacks and long-term prophylaxis aimed at reducing their frequency and severity. American guidelines list plasma-derived C1-INH supplementation in i.v. or s.c. form or the administration of a monoclonal antibody against plasma kallikrein as first-line prophylactic treatments for this condition.

Open-Label Extension of the COMPACT Study

The long-term efficacy of s.c. C1-INH prophylactic supplementation in patients with HAE was evaluated in the open-label extension of the phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Patients with HAE ages 6 and older who experienced at least four attacks in the two months prior to treatment initiation were included. These included previously untreated patients and those pre-treated in the COMPACT study. Participants were randomized to receive s.c. C1-INH at 40 or 60 IU/kg twice a week for 52 weeks, with a subgroup treated for more than 12 months.

The primary parameter monitored was long-term safety. Secondary efficacy parameters included the frequency of attacks, the proportion of patients responding to treatment (defined as a ≥ 50% decrease in attack frequency), the use of rescue medication, the duration of attacks, and the number of days with angioedema symptoms.

Results

A total of 126 patients were enrolled, with 63 receiving s.c. C1-INH at 60 IU/kg and 63 at 40 IU/kg.

Safety Profile

The most common adverse effect was an injection site reaction (0.06 events per injection in the 60 IU/kg group). Other events included nasopharyngitis, headache, and upper respiratory tract infections. 99% of adverse events were non-serious, 87% were mild, and 97% resolved.

Efficacy Profile

The published study indicates the efficacy results for 63 patients treated with s.c. C1-INH at 60 IU/kg (the dosage approved by the U.S. Food and Drug Administration /FDA/), including 24 patients who were treated for over a year. Of this population, 50.8% were already treated with s.c. C1-INH in the baseline study. The frequency of attacks during treatment was 0.09 per month and 1.0 per year. Two-thirds of patients used rescue medication less than once a year. For the subgroup treated for > 12 months, the attack frequency was 0.017/month and 0.199/year. Half of the patients (12) were attack-free for the entire study duration, and 3 (12.5%) had < 1 attack per year.

Conclusion

s.c. C1-INH supplementation represents a significant advancement in the treatment of hereditary angioedema caused by C1-INH deficiency. As demonstrated by the COMPACT study extension, including patients treated for over a year, long-term prophylaxis with s.c. C1-INH leads to a sustained decrease in attack frequency and reduces the need for rescue medication. Many patients can live attack-free with this treatment, allowing them to achieve a relatively normal and high-quality life.

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Source: Craig T., Feuersenger H., Pragst I., Dang J. Prophylactic therapy with subcutaneous C1-inhibitor is associated with sustained symptom control in patients with hereditary angioedema. Allergy Asthma Proc 2022 May 1; 43 (3): 202−208, doi: 10.2500/aap.2022.43.220016.