Positive Phase 2 Analyses Highlight Therapeutic Potential of Imlifidase in Guillain-Barré Syndrome

Hitto Kaufmann

Newly announced data from 15-HMedldeS-09, a single-arm phase 2 study (NCT03943589) of imlifidase (Hansa Biopharma), showed that treatment with the immunoglobulin (IgG)-cleaving enzyme resulted in improved functional status among patients with Guillain-Barré syndrome (GBS). The company plans to publish data from the study, as well as from an indirect comparison analysis using sample data from the International Guillain-Barré Syndrome Outcome Study (IGOS).¹

In GBS, it is known that reducing IgG levels can deplete pathological antibodies, potentially halting disease progression, accelerating recovery, and lessening severity. In the study, patients with severe GBS treated with a single dose of imlifidase at 0.25 mg/kg with added intravenous immunoglobulin (IVIg) demonstrated rapid growth in recovery of muscle strength, fast return to independently walking, and a median time to independently walk—defined by Guillain-Barré Syndrome Disability Scale (GBS DS) scores of 2 or less—by 16 days of treatment.

The efficacy analysis included 27 confirmed GBS cases after 3 were re-diagnosed. After 1 week of treatment, 37% of patients were able to independently walk and the mean improvement in muscle strength was 10.7 points as assessed by Medical Research Council sum score. Patients treated with the investigational agent demonstrated a median improvement of at least 1 grade on the GBS DS in 6 days, with 67% walking independently and 40.7% regaining the ability to run by 8 weeks. At 6 months, 63% of patients could run or had no functional disability (GBS DS ≤1).

"Our Phase 2 study results and the indirect treatment comparison with IGOS are critically important. Together they demonstrate the significant role imlifidase may play in future treatment options for patients with GBS,” Hitto Kaufmann, chief research & development officer at Hansa Biopharma, said in a statement.¹ “Unlike other molecules, imlifidase can effectively and very rapidly remove IgG through enzymatic cleavage - halting the progression of nerve damage associated with GBS and stopping disease progression."

Kauffman added, “The main goal of improved GBS treatments is to stop nerve damage early, reducing the time of hospitalization and support patients in regaining independence sooner. These findings underscore the role pathogenic IgG plays in severity and progression of GBS, and the clear potential of imlifidase to address unmet need in IgG-driven autoimmune diseases where faster acting treatment options are needed."

Hansa Biopharma also released findings from an indirect treatment comparison analysis that pinned 15-HMedldeS-09 study data against that from the IGOS, a worldwide real-world prospective study. The study analysis featured 754 patients with severe GBS treated with IVIg from IGOS vs the 27 participants in 15-HMedldeS-09 who were treated with the combination of imlifidase and IVIG. Overall, results showed that those in the combined treatment group experienced significantly faster improvement in disability, as measured by the GBS DS.

When comparing the 2 treatment groups, those on the combination approach of imlifidase and IVIg improved by at least 1 step on the GBS DS, 3 weeks sooner (P = .002), and returned to independently walking 6 weeks sooner than the IGOS real-world comparator group (P = .03). This group was also 6.4 times more likely (95% CI, 2.3-17.5; P <.0001) to walk independently at 1 week and 4.2 times more likely (95% CI, 1.6-11.5; P = .005) at 4 weeks. For this comparison, investigators matched and weighted both groups for various prognostic factors including time from weakness onset to treatment initiation and baseline value for age, autonomic disfunction, cranial nerve involvement, GBS DS, and MRC sum score.

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"In the treatment of GBS and subsequent recovery process, early improvement and the ability to walk independently are important clinical milestones as they indicate a return to basic mobility and independence, and to an improved quality of life for patients," principal investigator Shahram Attarian, head of the department of neuromuscular diseases and ALS at the Hopitaux de Marseille, in France, said in a statement.¹ "This analysis supports the potential role of imlifidase followed by standard of care IVIg as a potentially new treatment option in GBS. These are important results for patients and clinicians in the GBS community."

Historically, DBS, an inflammatory disease affecting 1-2 in 100,000 people annually, has been treated with IVIg. Imlifidase, which remains in development for other conditions like kidney transplantation, is a unique antibody-cleaving enzyme originating from Streptococcus pyogenes that specifically targets IgG and inhibits IgG-mediated immune response. The drug candidate is designed to eliminate pathogenic IgG, inhibiting previously cleaved IgG antibodies within hours of administration.

Hansa also has another novel immunomodulating therapy, HNSA-5487, that is currently being assessed in the context of chronic autoimmune conditions. Recently, the company announced positive 12-month data from its NICE-1 trial, a first-in-human study of HNSA-5487 in healthy adult participants. All told, results from the double-blind, placebo-controlled trial revealed that treatment with the agent resulted in highly robust reduction of IgG levels by more than 95% within a few hours post treatment.²

In NICE-1, single ascending doses of HNSA-5487 were considered safe and well tolerated, with no serious adverse events (AEs) observed. Overall, the therapy demonstrated lower pre-treatment anti-drug antibody (ADA) levels and significantly reduced ADA responses when compared with imlifidase. Following a significant reduction of IgG levels, a 12-month follow-up showed that these levels returned to normal range 6 months after initial dosing.

REFERENCES
1. Hansa Biopharma announces positive full results from 15-HMedIdeS-09 Phase 2 study and comparative analysis of imlifidase in patients with Guillain-Barré Syndrome. News release. Hansa Biopharma. December 17, 2024. Accessed December 23, 2024. https://www.prnewswire.com/news-releases/hansa-biopharma-announces-positive-full-results-from-15-hmedides-09-phase-2-study-and-comparative-analysis-of-imlifidase-in-patients-with-guillain-barre-syndrome-302334285.html
2. Hansa Biopharma's HNSA-5487 Achieved Rapid and Highly Robust IgG Reduction by More Than 95% and Clear Redosing Potential in First-in-Human Trial. News release. Hansa Biopharma. October 7, 2024. Accessed December 23, 2024. https://www.prnewswire.com/news-releases/hansa-biopharmas-hnsa-5487-achieved-rapid-and-highly-robust-igg-reduction-by-more-than-95-and-clear-redosing-potential-in-first-in-human-trial-302268672.html