Continuous Relapse Prevention1-3
Relapse Data
After transitioning from IVIg
Hizentra helps patients continue to live relapse free2
Primary end point: Relapse or withdrawal was significantly reduced vs placebo2
- Relapse or withdrawal rate: 38.6% Hizentra 0.2 g/kg (n=22/57; P=0.007), 32.8% Hizentra 0.4 g/kg (n=19/58; P<0.001) vs 63.2% placebo (n=36/57)
MOST PATIENTS REMAINED RELAPSE-FREE DURING THE PIVOTAL PATH STUDY (N=172) AND DURING THE LONG-TERM EXTENSION STUDY (N=82)*
PATH STUDY2
Patients without CIDP relapse† sensitivity analysis
PATH EXTENSION STUDY3‡
*The 0.4 g/kg dose achieved a numerically lower rate of relapse compared to the 0.2 g/kg dose, but the difference was not statistically significant.
†Data shown only consider CIDP relapse based on the adjusted INCAT score (relapse sensitivity analysis). All patients who withdrew for reasons other than relapse were assumed not to have had a relapse.2
‡Relapse rates refer to all subjects in the extension study, irrespective of treatment and status at the end of the PATH study.3
Titrating up provided
symptom relief3
In the PATH extension study, patients on the 0.2 g/kg dose who experienced a relapse were titrated up to 0.4 g/kg, which provided symptom relief/improvement for 92% (24/26) of patients.
Study Design
PATH & OLE study design
§PATH Study Design: A randomized, multicenter, double-blind, placebo-controlled, parallel-group, Phase 3 study of 2 doses of weekly Hizentra vs placebo for the maintenance treatment of CIDP. Subjects who had completed the PATH study or who had successfully been rescued from a relapse could participate in the open-label study.
¶Extension Study Design: A 48-week, open-label, prospective extension study to PATH. 82 patients were enrolled: 62 were started on 0.4 g/kg weekly infusion of Hizentra, and 20 were started on 0.2 g/kg weekly. If clinically stable, patients on 0.4 g/kg were switched to 0.2 g/kg after 24 weeks. Upon CIDP relapse on 0.2 g/kg dose, 0.4 g/kg was either initiated or reinitiated. Due to the study design, the same subject could have received both doses during the study. Relapse was defined as a ≥1-point increase in adjusted INCAT score vs baseline.3
Mobility Data
Hizentra helps keep patients mobile2
Hizentra maintained patients’ functional ability across multiple secondary end points2
As demonstrated through I-RODS¶ scores vs placebo
Median change from baseline to last postdose observation was -3.0 points for the placebo group, -2.0 points for the 0.2 g/kg Hizentra group, and 0.0 for the 0.4 g/kg Hizentra group (P=0.0002 overall).#
¶The I-RODS measures a patient’s ability to perform a wide range of activities ranging from easy tasks, like reading a book, eating, and brushing teeth, to more difficult tasks such as standing for extended periods of time or running.
#Overall P values are based on both Hizentra dosing groups compared to placebo. The difference between the 0.2 g/kg Hizentra group and the placebo group was not significant.
With –1.7 kPa median change from baseline (P=0.0223).**
**Overall P values are based on both Hizentra dosing groups compared to placebo. Grip strength change was for dominant hand.
With no change in functional ability
- 0.0 median change from baseline (P=0.0026)†† for MRC
- 0.0 median change from baseline (P<0.0001)†† for INCAT
††Overall P values are based on both Hizentra dosing groups compared to placebo. The MRC sum score was assessed in the following 8 bilateral muscle pairs: shoulder abduction, elbow flexion, wrist extension, index finger abduction, hip flexion, knee extension, foot dorsiflexion, and great toe dorsiflexion. The INCAT score is a 10-point scale that covers the functionality of legs and arms.
||Statistically significant vs placebo at the last postdose observation.2
Quality-of-life results for patients on Hizentra‡‡
of patients surveyed (n=92/107) felt that Hizentra maintained or improved mobility vs 73% (n=32/44) for placebo2
‡‡Based on exploratory EQ-5D results, which found that 79% of patients (n=85/107) reported maintained mobility, while 6.5% (n=7/107) reported improved mobility.2
Abbreviations: CIDP, chronic inflammatory demyelinating polyneuropathy; EQ-5D, EuroQoL 5-Dimension Questionnaire; I-RODS, Inflammatory Rasch-built Overall Disability Scale; INCAT, Inflammatory Neuropathy Cause and Treatment; IVIg, intravenous immunoglobulin; MRC, Medical Research Council; OLE, open-label extension; SCIg, subcutaneous immunoglobulin.
References: 1. Tortorici MA, Yuraszeck T, Cornblath D, et al. CPT Pharmacometrics Syst Pharmacol. 2021;10(8):839-850. doi:10.1002/psp4.12647 2. van Schaik IN, Bril V, van Geloven N, et al. Lancet Neurol. 2018;17(1):35-46. doi:10.1016/S1474-4422(17)30378-2 3. van Schaik IN, Mielke O, Bril V, et al. Neurol Neuroimmunol Neuroinflamm. 2019;6(5):e590. doi:10.1212/ NXI.0000000000000590
IMPORTANT SAFETY INFORMATION
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.
Indications
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.
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.
Hizentra is manufactured by CSL Behring AG and distributed by CSL Behring LLC.
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