Hizentra therapy effective for primary immunodeficiency patients

CSL BehringOct 7 2010

Hizentra® (IgPro20) provides primary immunodeficiency (PI) patients with a safe and effective alternative to other immunoglobulin therapies when given in equivalent doses, according to Phase III pivotal trial data presented today at the XIVth Meeting of the European Society for Immunodeficiencies (ESID). Hizentra, the first and only 20 percent SCIg developed for subcutaneous (i.e., under the skin) administration, can be stored at room temperature over its entire 24-month shelf life given its formulation with L-proline.

The data show that adult and pediatric patients who were administered Hizentra after being on other Ig therapies experienced similar or increased immunoglobulin (Ig) trough levels, were protected from infections, and that Hizentra was well-tolerated.  The trough represents the point at which levels of serum IgG - the antibody molecules needed to ensure the body's immune response functions properly - are at their lowest. Maintaining steady-state IgG levels without low troughs or high peaks is the goal of successful Ig treatment in PI.  

"These studies demonstrate that PI patients who switched to Hizentra from a dose-equivalent immunoglobulin therapy administered either intravenously or subcutaneously increased or maintained (Ig) trough levels and were protected against infections," said Stephen Jolles, M.D., University Hospital of Wales, Cardiff, U.K. and study investigator. "We see that Hizentra provides a therapeutic option as safe and effective as other treatments for PI. Further, the 20 percent concentration was infused without an increase in local side effects and may allow patients to infuse less volume more quickly, potentially enhancing its convenience."

Replacement immunoglobulin therapy with intravenous IG (IVIg) has long been considered the gold standard for lifelong treatment of primary immunodeficiency. In recent years, however, subcutaneously-administered Ig treatment (SCIg) has gained wide acceptance as an alternative therapy. Self-administered weekly, SCIg treatment offers patients convenience, while providing the body with sustained levels of serum IgG, the antibody molecules needed to ensure the immune response functions properly. SCIg can also reduce the need for costly healthcare resources often associated with intravenously-administered (IVIg) therapy.

Study Design

In the study, 51 PI patients (3 to 60 years old), previously treated with IVIg or SCIg therapies received weekly subcutaneous infusions of Hizentra at doses equivalent to those used in previous treatment. The primary endpoint was achievement of IgG trough levels similar to those associated with previous treatment, measured before infusions 12 through 17. The Phase III study consisted of a 12-week wash-in/wash-out period and a 28-week efficacy period.

Findings demonstrated that the mean trough level of 8.10 g/L achieved with Hizentra was similar to the overall mean IgG trough level of 7.49 g/L found in the study group pre-trial. The mean IgG trough level increased by 17.7 percent in patients previously treated with IVIg (from 6.78 g/L to 7.98 g/L), but remained similar in patients previously treated with SCIg (change from  8.43 g/L to 8.27 g/L). During the efficacy period, no serious bacterial infections (SBIs) were reported; 36 patients experienced a non-serious infection. Only half of patients reported local reactions, mainly after the first infusion. Almost all (98.7 percent) adverse events (AEs) were mild or moderate in intensity. Three patients discontinued due to related AEs. No related serious AEs were reported.

A sub-group of the study consisted of a pediatric cohort, children (age range 2-11 years) and adolescents (age range 12-15 years). 17 children and 5 adolescents previously treated with IVIg or SCIg therapies were recruited into the study and received weekly subcutaneous infusions of Hizentra at doses equivalent to those used in previous treatment. Findings demonstrated a 13.3 percent increase in mean IgG trough levels in children from 6.95 g/L to 7.86 g/L. However, two thirds of children had used IVIg before switching to Hizentra.  Adolescents, where 4 out of 5 patients were already SCIg-pretreated, showed similar IgG trough levels before and during the study (7.99 g/L versus 7.91 g/L, respectively). During the efficacy period, no SBIs were reported, however a child with a history of recurrent severe pneumonias experienced an SBI of pneumonia during the wash-in/wash-out period. Non-serious infections were experienced by 15 children and 3 adolescents. Related and temporarily associated AEs were observed in 7 children and 2 adolescents. Serious AEs (3) and AEs leading to discontinuation (2), all unrelated, were reported only in the children.