PHILADELPHIA, PA – April 21, 2020 – Global biotherapeutics leader CSL Behring today announced that a clinical study examining faster infusion rates and higher volumes than currently approved for Hizentra® (Immune Globulin Subcutaneous [Human] 20% Liquid) (SCIg) in patients with primary immunodeficiency (PI) met its primary endpoint. The study also evaluated the feasibility of manual push administration with Hizentra, a new method that would eliminate the need for an infusion pump to administer the SCIg. The research, originally scheduled to be presented at the 2020 AAAAI Annual Meeting that was canceled due to coronavirus disease 2019 (COVID-19), was published in an online supplement to The Journal of Allergy and Clinical Immunology. Results of three analyses, all stemming from the HILO (Hizentra Label Optimization) study, conducted by CSL Behring, were also published in the American Academy of Allergy, Asthma & Immunology (AAAAI) online poster library: Poster 097, Poster 697 and Poster 699.
“People living with PI must carefully manage their health with regular infusions of Ig therapy. As such, we are looking for solutions to ease the treatment burden and simplify the process,” said John Anderson, M.D., Research Director, Alabama Allergy & Asthma Center. “With this new research, there is data to support that Hizentra can be safely infused at a faster flow rate or higher volume than previously approved, potentially offering patients shorter infusion times, a potential decrease in the number of needle sticks and greater flexibility for them to individualize their infusion experience.”
In the study, researchers evaluated patients in three cohorts, the pump-assisted flow rate cohort with a baseline infusion rate of 25 mL/hour per injection site, pump-assisted volume cohort with a baseline infusion volume of 25 mL per injection site and manual push flow rate cohort with a baseline infusion rate of 0.5 mL/minute (30 mL/hour per injection site). Positive results were observed from the expanded infusion parameters of Hizentra for most patients across all three cohorts.
“Understanding the needs of patients with PI and how we can improve their treatment experience by optimizing our therapies is a critical focus for us,” said Mittie Doyle, M.D., Vice President, Research and Development, Immunology Therapeutic Area at CSL Behring. “This study is yet another example of how we are delivering on our promise to patients with PI to help them better manage their health challenges.”
About the HILO Study
A multicenter, open-label, parallel-arm, non-randomized study, HILO enrolled 49 adult and pediatric patients with PI who were on a stable dose of Hizentra therapy. Patients were enrolled in either a pump-assisted volume cohort (n=15), pump-assisted flow rate cohort (n=18) or manual push administration flow rate cohort (n=16). Assignments were based on prior experience with pump-assisted infusions or manual push administration infusions. The primary endpoint was the responder rate within each cohort and for each infusion parameter level; secondary endpoints examined safety and tolerability. For the two pump-assisted cohorts, responder rates were defined as the percentage of patients who successfully completed ≥75% of planned infusions. For the manual push administration cohort, responder rates were defined as the percentage of patients who completed at least 60% of infusions at each flow rate and who completed the full dose per scheduled infusion without interruptions for any reason.
Each cohort tested increasing infusion levels of Hizentra. After four consecutive weeks of receiving the same infusion level, qualifying participants moved to the next higher infusion level. Each infusion parameter level was tested for four weeks, after which responders were switched to the next level. The cohorts included:
- Pump-assisted volume cohort (which consisted of weekly infusions, with volume per injection site of 25 mL, 40 mL and 50 mL)
- Pump-assisted flow rate cohort (which consisted of weekly infusions, with flow rate per injection site of 25 mL/hour, 50 mL/hour, 75 mL/hour and 100 mL/hour)
- Manual push administration flow rate cohort (which consisted of two to seven infusions per week, with flow rate per injection site of 0.5mL/minute (30 mL/hour), 1 mL/minute (60 mL/hour) and 2 mL/minute (120 mL/hour).
Researchers observed the following results and responder rates for the three cohorts.
- Pump-assisted cohort results:
- Responder rates for the pump-assisted volume cohort were 86.7% (25 mL) and 73.3% (40 and 50 mL), while responder rates for the pump-assisted flow rate cohort were 77.8% (25 and 50 mL/hour), 66.7% (75 mL/hour) and 61.1% (100 mL/hour).
- Dose and volume adherence rates were ≥90% in all patients of the volume cohort, and 83.3% in patients in the flow rate cohort (<90% in three patients).
- Mean serum immunoglobulin G (IgG) trough levels (g/L) were similar between Day 1 and end of the study for the volume cohort and the flow rate cohort.
- Manual push administration cohort results:
- Responder rates were 100% (0.5 and 1 mL/minute) and 87.5% (2 mL/minute), with 98.5-100% of infusions completed per the planned schedule.
- Compliance rates were ≥90% in all patients but one.
- Mean serum IgG trough levels were similar between Day 1 and the end of the study.
The final analysis examined the rate of treatment-emergent adverse event (TEAE) frequency, type, intensity or duration across all three cohorts. Low rates of TEAEs/infusion were observed across all cohorts, with mild to moderate infusion site reaction being the most common. Specifically, TEAE rates/infusion were 0.145, 0.228 and 0.085 in the pump-assisted volume cohort, pump-assisted flow rate cohort and manual push administration flow rate cohort, respectively. There was no clinically meaningful difference in TEAE frequency, type, intensity or duration among the three cohorts and rates of TEAEs/infusion did not increase with expanded infusion parameters.
About Primary Immunodeficiency (PI)
PI diseases are a group of more than 400 rare, chronic disorders in which part of the body's immune system is missing or malfunctioning. Patients with PI commonly have frequent infections, reoccurring infections, infections that won't go away or unusually severe infections. As a result, patients may face repeated rounds of antibiotics or be hospitalized for treatment. Many people living with PI have missed school, work or time with family and friends.
Registered in more than 60 countries, Hizentra is the world's most prescribed subcutaneous immune globulin to treat PI, and has a proven track record of safety, efficacy and tolerability, with more than 6.7 million exposures worldwide since 2010. Hizentra was first approved by the U.S. FDA in March 2010 for the treatment of patients with PI and was approved in March 2018 for the treatment of adults with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment. For more information about Hizentra, including the U.S. prescribing information, visit www.hizentra.com.
CSL Behring: Continuing to Innovate as a World Leader in Immune Globulin Therapies
CSL Behring is a world leader in immune globulin therapies with the longest-standing history in plasma-derived therapies of any immune globulin manufacturer. The company’s continuous pursuit of research and product innovation has been a catalyst for industry-wide breakthroughs, including the introduction of the first 20% subcutaneous immune globulin for patients with PI. That innovation continues today with the promise to continually better the treatment experience for patients.
Important Safety Information for the U.S.
Hizentra®, Immune Globulin Subcutaneous (Human), 20% Liquid, is indicated for:
- Treatment of primary immunodeficiency (PI) in adults and pediatric patients 2 years and older.
- Maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment.
- Limitation of Use: Maintenance therapy in CIDP has been systematically studied for 6 months and for a further 12 months in a follow-up study. Continued maintenance beyond these periods should be individualized based on patient response and need for continued therapy.
For subcutaneous infusion only.
WARNING: Thrombosis may occur with immune globulin products, including Hizentra. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors.
For patients at risk of thrombosis, administer Hizentra at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.
Hizentra is contraindicated in patients with a history of anaphylactic or severe systemic reaction to human immune globulin (Ig) or components of Hizentra (eg, polysorbate 80), as well as in patients with immunoglobulin A deficiency with antibodies against IgA and a history of hypersensitivity. Because Hizentra contains L-proline as stabilizer, use in patients with hyperprolinemia is contraindicated.
IgA-deficient patients with anti-IgA antibodies are at greater risk of severe hypersensitivity and anaphylactic reactions. Thrombosis may occur following treatment with Ig products, including Hizentra.
Monitor patients for aseptic meningitis syndrome (AMS), which may occur following treatment with Ig products, including Hizentra. In patients at risk of acute renal failure, monitor renal function, including blood urea nitrogen, serum creatinine and urine output. In addition, monitor patients for clinical signs of hemolysis or pulmonary adverse reactions (eg, transfusion-related acute lung injury [TRALI]).
Hizentra is derived from human blood. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), cannot be completely eliminated.
The most common adverse reactions (observed in 5% of study subjects) were local infusion-site reactions, as well as headache, diarrhea, fatigue, back pain, nausea, extremity pain, cough, upper respiratory tract infection, rash, pruritus, vomiting, upper abdominal pain, migraine, arthralgia, pain, fall, and nasopharyngitis.
The passive transfer of antibodies can interfere with response to live virus vaccines and lead to misinterpretation of serologic test results.
Please see full prescribing information for Hizentra, including boxed warning.
To report SUSPECTED ADVERSE REACTIONS, contact the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
About CSL Behring
CSL Behring is a global biotherapeutics leader driven by its promise to save lives. Focused on serving patients’ needs by using the latest technologies, the company develops and delivers innovative therapies that are used to treat coagulation disorders, primary immune deficiencies, hereditary angioedema, respiratory disease, and neurological disorders. The company’s products are also used in cardiac surgery, burn treatment and to prevent hemolytic disease of the newborn.
CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma. The parent company, CSL Limited (ASX:CSL;USOTC:CSLLY), headquartered in Melbourne, Australia, employs more than 25,000 people worldwide, and delivers its life-saving therapies to people in more than 70 countries. For inspiring stories about the promise of biotechnology, visit Vita at CSLBehring.com/vita and follow us on Twitter.com/CSLBehring.
Dana Lynch, CSL Behring
Office: (610) 878-4545
Mobile: (215) 532 5564