The treatment is the first patient-infused subcutaneous formulation of immunoglobulin to gain approval for CIDP.
Todd Levine, MD
The FDA has approved a subcutaneous immunoglobulin (Immune Globulin Subcutaneous; Hizentra) as a treatment for adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment, according to a statement from CSL Behring, the developer of the therapy.
The approval was based on findings from the phase III PATH study, wherein 2 doses of subcutaneous immunoglobulin (0.4 g/kg and 0.2 g/kg) cut the number of relapses in half compared with placebo. In the 0.4 and 0.2 g/kg groups, the rate of relapse or withdrawal was 32.8% and 38.6%, respectively, compared with 63.2% with placebo.
The approval marks the first for a subcutaneous formulation of immunoglobulin for CIDP. The treatment is self-infused at home by the patient.
“As a practicing neurologist treating patients with CIDP, I am excited to have a safe and effective subcutaneous treatment option to offer my patients who are interested in more treatment flexibility and control in their busy lives,” Todd Levine, MD, Phoenix Neurological Associates.
In the double-blind PATH study, patients were randomized in a 1:1:1 ratio to placebo (n = 57) or weekly doses of subcutaneous immunoglobulin at 0.2 g/kg (n = 57) or 0.4 g/kg (n = 58). Patients self-infused the treatment across 4 sites for 1 hour at 20 mL/hour. The median age of patients was between 55 and 59 years across arms. Prior to the randomized portion of the study, patients were stabilized with intravenous immunoglobulin.
The high-dose of subcutaneous immunoglobulin resulted in a 62% reduction in the risk of relapse or withdrawal compared with placebo (HR, 0.38; 95% CI, 0.22-0.67; P = .0005). in the low-risk group, treatment reduced the risk of relapse or withdrawal by 51% compared with placebo (95% CI, 0.29-0.84; P = .007). There was not a statistically significant difference between the two treatment arms (HR, 0.80; 95% CI, 0.43-1.49; P = .48).
The absolute risk reduction (ARR) compared with the placebo arm was 30% for the high-dose and 25% for the low-dose. The ARR was 6% between the high and the low dose. At the time of the analysis, 81% of patients in the high-dose group and 67% in the low-dose group remained relapse-free.
Overall, 9% of patients withdrew for reasons other than relapse. When these patients were excluded and only relapse was considered, the relapse-rate was 19% with the high dose and 33.3% with the low dose compared with 56.1% with placebo. In this analysis, 81% and 67% of those in the high- and low-dose groups, respectively, remained relapse-free at 24 weeks versus 44% with placebo.
“This new FDA approval for Hizentra marks a pivotal milestone for patients struggling with the disabling neurological effects of CIDP,” Andrew Cuthbertson, PhD, chief scientific officer and R&D director, CSL Limited, the parent company for CSL Behring, said in a statement.
“As the first and only subcutaneous immunoglobulin therapy approved to treat CIDP, and studied in the largest controlled clinical trial for CIDP, Hizentra offers patients a more convenient treatment option with proven efficacy and the flexibility and freedom to self-infuse at home," he said. "CSL Behring is deeply committed to delivering innovative therapies to patients with rare and serious diseases like CIDP, and today we are proud to now offer a portfolio of immunoglobulin therapies for CIDP.”
Treatment-emergent adverse events were experienced by 37% of patients in the placebo group compared with 58% and 52% in the low- and high-dose groups, respectively. The most common events were infusion site reactions, which were seen in 11% of patients in the placebo arm compared with 28% and 31% of those in the low- and high-dose groups, respectively. Other events with the subcutaneous immunoglobulin included infections and infestations (14% with placebo vs 23% and 10%) and musculoskeletal and connective tissue disorders (7% vs 18% and 10%).
“Despite available treatment options, many CIDP patients continue to struggle with daily disease and lifestyle challenges, making continued research and innovation critical,” Lisa Butler, executive director of the GBS|CIDP Foundation International, said in a statement. “The approval of Hizentra offers patients who were once burdened by traveling to the infusion center or hospital the flexibility to self-administer their treatment at a time, place, and on a schedule that’s convenient for them.”
The subcutaneous immunoglobulin infusion initially received FDA approval in 2010. The agent is also indicated for the treatment of patients with primary immunodeficiency in adults and pediatric patients 2 years of age and older.
van Shaik IN, Bril V, van Geloven N, et al. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2018;17(1):35-46.