PC2178: Long-term Efficacy, Safety, and Tolerability of a Subcutaneous Immunoglobulin 16.5% (cutaquig®) in the Treatment of Adult and Pediatric Patients with Primary Immunodeficiencies

Background: The current analysis presents data from a pivotal Phase 3 study with cutaquig® in children and adults with primary immunodeficiencies (PID; NCT01888484) and its long-term extension (NCT03907241). De novo patients (previously on SCIg treatment for at least 12 months) and patients from the main study were enrolled in the extension study.

Methods: The two studies investigated the long-term efficacy, safety, and tolerability of cutaquig® with a unique long-term follow-up of more than 4 years for nearly half of the patients. Cutaquig® was administered once weekly in the main study for up to 70 weeks and up to 168 weeks in the extension study, for a total of up to 238 weeks. The primary objective of the main study was to assess the efficacy of cutaquig® in preventing serious bacterial infections (SBIs). The main objective in the extension study was to examine the safety profile of long-term administration and confirm continued efficacy.

Results: Seventy-five patients received 4,462 infusions in the main study and 27 patients received 2,777 infusions throughout the extension study. The maximum rate of infusion per site was 25 mL/h in children and 52 mL/h in adults. In children and adults, the mean maximum infusion flow rate increased from the mean of 39.04 mL/h and 60.4 mL/h in the main study to 42.2 mL/h and 91.9 mL/h, respectively, in the extension, with no increase in tolerability issues
There were no incidences of SBIs, and the annual rate of other infections was 3.3 (95% CI 2.4, 4.5) in the main study. One unrelated SBI (high fever of unknown origin) was recorded in the extension study in an adult participant (rate of 0.02 [upper 99% CI 0.19]). The annual rate of all infections in the extension study was 2.2 (95% CI 1.2, 3.9), which was decreased compared with the main study (Fig. 1).
The plasma IgG trough levels were nearly constant during the study. No patient had IgG trough levels < 5 g/L. A population PK study confirmed every-other-week dosing regimen.
The incidence of related systemic AEs (excluding ISRs and infections) diminished from 14.7% to 7.4% in the extension study. Over both studies, the most common reactions in children were asthma, cough, and vomiting (10.5% each) and in adults headaches (18.6%).
Of the 7,239 infusions administered over the course of both studies, 85.0% (6151 infusions) were not associated with an infusion site reaction (ISR). Transient ISRs included mainly redness, swelling, and pain at site. The majority (88%) of ISRs were mild. The rates of ISRs declined over time (Fig. 2).

Conclusion: In conclusion, this unique prospective, up to 4-year long-term use of cutaquig® showed effective protection from SBIs, and low rates of local and systemic adverse reactions, supporting the favorable safety profile of cutaquig®.