In the phase 2 study, patients with Guillian-Barré syndrome will receive imlifidase on day 1, followed with intravenous immunoglobulin on days 3-7, with outcomes of safety and change in disability.
According to a recent announcement, enrollment for the phase 2, open-label, multicenter study (NCT03943589) of Hansa Biopharma’s imlifidase in patients with Guillain-Barré syndrome (GBS) has completed, with topline data expected to be released during the second half of 2023.1
GBS, a rare, acute, paralyzing, inflammatory disease of the peripheral nervous system, affects 1-2 in 100,000 people annually, and has been typically treated with intravenous immunoglobulin (IVIG). Developed by Hansa, imlifidase is a unique antibody-cleaving enzyme originating from Streptococcus pyogenes that specifically targets IgG and inhibits IgG-mediated immune response. The agent is designed to eliminate pathogenic IgG, inhibiting previously cleaved IgG antibodies within hours of administration.
The phase 2 study will include approximately 30 patients who are eligible for IVIG treatment based on current practice, essentially, a GBS disability score greater than 3 and within 10 days of onset of weakness. All patients will receive 1 dose of imlifidase 0.25 mg/kg on day 1, followed by 0.4 g/kg of IVIG, administered for 5 consecutive days, starting on day 3, at least 48 hours after imlifidase administration. Patients will be assessed on safety, as measured by adverse events (AEs), and change in disability at 4 weeks using the 6-point GBS disability score.
"This phase 2 study of imlifidase in GBS is an important next step in understanding the role of our antibody-cleaving enzyme technology in treating rare immunologic conditions,” Soren Tulstrup, president and chief executive officer, Hansa Biopharma, said in a statement.1 "We remain fully committed to advancing the science and delivering innovative therapies to the many patients affected by severe immunologic conditions."
Efficacy parameters will be compared with a control group consisting of up to 4 individuals from the International Guillain-Barré Syndrome Outcome Study (IGOS) database. Matching will be done on geographical locations, age, presence of diarrhea, and severity of condition. The outcome of the comparative efficacy analysis between the 2 cohorts is expected to be shared during 2024.
Investigators hope that a reduction of pathological antibodies caused by imlifidase will results in aborted progression, quicker recovery, and less severe disease. In addition to the primary outcomes, the trial will also assess secondary measures of mean change in disability based on GBS disability score, ability to walk unaided at 4, 8, and 26 weeks, time to improvement by at least 1 GBS disability score grade, and change in Rasch-built Overall Disability scale, among others.
"In the treatment of GBS, a timely diagnosis and treatment are crucial to reducing the severity of the symptoms and minimizing long term damage. With a unique treatment approach focused on rapidly and effectively reducing IgG levels, imlifidase represents a potentially new way to treat GBS patients,” international coordinating principal investigator Shahram Attarian, head, Department of Neuromuscular Diseases and ALS, Hopitaux Universitaires de Marseille, said in a statement.
In the US, the FDA previously granted imlifidase orphan drug designation for the treatment of antibody-mediated organ rejection in solid organ transplant patients in September 2015, and later received the same designation in February 2018 for GBS. Later that year, in July 2018, it received orphan drug designation for anti-GBM antibody disease, also known as Goodpasture’s disease.
Following a successful pre-investigational new drug application (IND) meeting with the FDA in late 2021, Hansa announced it would proceed with a phase 3 study assessing the agent in anti-GBM. The trial includes 50 patients with anti-GBM disease who are randomly assigned either standard of care or imlifidase plus standard of care, with the primary end point of renal function, assessed by means of eGFR, at 6 months.