FDA Approves CSL Behring's Immune Globulin Subcutaneous Prefilled Syringe for PI and CIDP

Lisa Butler

In recent news, the FDA approved CSL Behring's 50mL/10gm prefilled syringe for immune subcutaneous immunoglobulin (Hizentra) for patients living with primary immunodeficiency (PI) or chronic inflammatory demyelinating polyneuropathy (CIDP). The treatment is the first and only immune globulin (Ig) available in a ready-to-use prefilled syringe and comes in a full range of sizes to meet the needs of the patient.¹

In 2010, subcutaneous immunoglobulin was initially approved to treat PI, a genetic defect of the immune system which leads to frequent and severe infections in patients. Following the approval, in March 2018, the subcutaneous immunoglobulin received a new indication for use as maintenance therapy in adults with CIDP, a rare neurological disorder that causes weakness, paralysis, and sensory disturbance.

"When managing a lifelong rare disease or chronic condition, it is important to have treatment options that offer flexibility and convenience as a person's needs can change over time," said Lisa Butler, executive director, GBS|CIDP Foundation said in a statement.¹ "Having prefilled syringes available that allow people with conditions such as CIDP to administer their treatment at home, on their schedule, can help decrease treatment burden."

When subcutaneous immunoglobulin was approved for CIDP and PI, it was administered as an infusion in up to 8 different parts of the patient's body each time. The IG was administered as a treatment weekly for patients with CIDP and infused as often as every day up to every 2 weeks for patients with PI.

In one of the clinical trials conducted in the US, 49 adult and pediatric patients with PI were treated, and 38 of them were analyzed for efficacy with subcutaneous immunoglobulin. Initially, patients were treated with monthly treatments of immune globulin intravenous infusion (IGIV) and then switched to weekly doses of subcutaneous immunoglobulin. No serious bacterial infections were reported and the annual rate was 2.76 infections/year for any infection. The total number of patients requiring antibiotic use was 27, the number of days out of work or school because of infections was 71, and the total number of days hospitalized was 7.⁴

During the efficacy period, the average trough levels increased by 24.2% when comparing subcutaneous immunoglobulin to IGIV, accounting for the 49% increased dose of subcutaneous immunoglobulin from the previous IGIV dose. Similar studies were performed in Europe with 51 adult and pediatric patients with PI switching from monthly IGIV to subcutaneous immunoglobulin where none of the patients developed a serious bacterial infection, and the annualized rate of infections was 5.18 infections per patient.

In a phase 3 trial, subcutaneous immunoglobulin 0.4 g/kg and 0.2 g/kg versus placebo was investigated in 172 adult patients with CIDP who were previously treated with the IGIV. CIDP relapse or withdrawal from the study was the efficacy end point which was determined by at least 1-point increase in adjusted inflammatory neuropathy cause and treatment score compared with baseline.

Both doses of subcutaneous immunoglobulin (0.4 g/kg and 0.2 g/kg) were superior to placebo (P < .001 and P = .007, respectively) when considering withdrawal and CIDP relapse. Notbaly, subcutaneous immunoglobulin doses were significantly superior to placebo, with CIDP relapse rates of 19.0% for 0.4 g/kg subcutaneous immunoglobulin , 33.3% for 0.2 g/kg subcutaneous immunoglobulin , and 56.1% for placebo (P < .001 and P = .012, respectively) when considering only relapse. In addition, 81%, 67%, and 44% of patients who received subcutaneous immunoglobulin 0.4 g/kg, subcutaneous immunoglobulin 0.2 g/kg, and placebo, respectively, remained relapse-free for up to 24 weeks.⁴

In the clinical trials, adverse events reported in at least 5% of patients were local reactions, headache, diarrhea, fatigue, back pain, nausea, upper respiratory tract infections, rash, vomiting, pruritis, migraine, abdominal pain, arthralgia, falls, and nasopharyngitis.³

"As part of our promise to meet the needs of people who rely on our life-saving therapies, we recognize the important value of offering people with PI or CIDP a larger prefilled syringe size option to effectively manage their condition," said Bob Lojewski, senior vice president and general manager, North America, CSL Behring said in a statement.¹ "We are proud to be at the forefront of delivering effective treatment options that also provide flexibility by allowing those with PI or CIDP to self-administer their treatments based on their specific needs and lifestyles."

In the US, the treatment is the most prescribed self-infused subcutaneous immune globulin for PI in the US and the first and only SCIg treatment approved for CIDP. The company announced that the 50mL prefilled syringe is set to be available in early 2024. Until then, subcutaneous immune globulin will continue to be available in 5mL, 10mL-and 20mL prefilled syringes as well as in 5mL, 10mL, 20mL, and 50mL vials.¹

REFERENCES
1. CSL Behring Receives FDA Approval for Hizentra (Immune Globulin Subcutaneous [Human] 20% Liquid) 50mL Prefilled Syringe. News Release. CSL Behring. Published April 18, 2023. Accessed April 18, 2023. https://www.prnewswire.com/news-releases/csl-behring-receives-fda-approval-for-hizentra-immune-globulin-subcutaneous-human-20-liquid-50ml-prefilled-syringe-301799492.html
2. FDA approves subcutaneous immunoglobulin (immune globulin subcutaneous [human] 20% liquid) for the treatment of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). New Release. CSL Behring. Updated March 16, 2018. Accessed April 2023, 2023.
3. Subcutaneous immunoglobulin [prescribing information]. Bern, Switzerland: CSL Behring; 2010. Accessed April 18, 2023. www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM203150.pdf