Data Support Hizentra® Efficacy, Safety After Dose-Equivalent Switch in Adult and Pediatric Patients with Primary Immunodeficiency

ISTANBUL, Oct. 7 /PRNewswire/ -- 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.

About Primary Immunodeficiency

Primary immunodeficiency (PI) is a group of more than 150 diseases that affect the cells, tissues and proteins of the immune system. In people with PI, the immune system is either absent or functioning inadequately, leaving them more susceptible to infection. For individuals with PI -- many of them children -- infections may not improve with treatment as expected, and may keep returning. As a result, patients may face repeated rounds of antibiotics or be hospitalized for treatment. Repeated infections can lead to organ damage, which, over time, can become life-threatening. Collectively, PIs affect an estimated 10 million people worldwide, and the incidence is estimated to be 1 in 10,000.

About Hizentra

Hizentra® (Immune Globulin Subcutaneous [Human]), the first and only 20 percent SCIg developed for subcutaneous use, is already approved in the US and in registration in the EU and Switzerland. It is stable at 25 degrees C for at least 24 months due to formulation with L-proline. In the US, Hizentra is indicated for the treatment of patients with primary immunodeficiency (PI), and contraindicated in individuals with a history of anaphylactic or severe systemic response to immune globulin preparations or components of Hizentra, and in persons with selective immunoglobulin A deficiency who have known antibody against IgA and a history of hypersensitivity. The most common drug-related adverse reactions, observed in 5 percent or more of subjects in the US clinical study, were local injection-site reactions, headache, vomiting, pain and fatigue. For more information, including full US prescribing information, visit http://www.hizentra.com/.

About CSL Behring

CSL Behring is a leader in the plasma protein therapeutics industry. Committed to saving lives and improving the quality of life for people with rare and serious diseases, the company manufactures and markets a range of plasma-derived and recombinant therapies worldwide. CSL Behring therapies are indicated for the treatment of coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies and inherited respiratory disease. The company's products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic diseases in newborns. CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL Limited (ASX: CSL), a biopharmaceutical company headquartered in Melbourne, Australia. For more information, visit www.cslbehring.com.

SOURCE CSL Behring