Octapharma has released results from its phase 3 superiority study evaluating PANZYGA® (immune globulin intravenous, human - ifas) 10% Liquid Preparation versus placebo in patients with pediatric acute-onset neuropsychiatric syndrome (PANS). While the trial missed its primary efficacy endpoint, it achieved statistical significance on a key secondary measure that reflects the broader impact of the condition.
Primary Endpoint Results
The study utilized the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score measured at 9 weeks as the primary endpoint for assessing PANZYGA effectiveness in reducing PANS symptom severity. From baseline to week 9, the PANZYGA group showed a mean improvement of 31.1% (SD 40.68) in CY-BOCS scores compared to 12.1% (SD 68.39) in the placebo group.
However, when researchers compared the CY-BOCS score ratio between the two groups at week 9, the difference was not statistically significant with a p-value of 0.072, failing to meet the primary endpoint threshold.
Significant Secondary Endpoint Achievement
Despite missing the primary endpoint, the study achieved statistical significance on the Clinical Global Impression-Improvement (CGI-I) score at week 9, a key secondary endpoint. The difference between groups was statistically significant with a p-value of 0.017, showing higher improvement in the IVIG group.
"While this Phase III trial did not meet its primary efficacy outcome of OCD symptom improvement measured by CY-BOCS, it revealed promising insights: the key secondary endpoint of Clinical Global Impression (CGI) showed statistically significant and clinically relevant improvement," said Principal Investigator Michael Daines, M.D., Division Chief of Pediatric Allergy and Immunology at the University of Arizona College of Medicine.
Crossover Analysis Reveals Sustained Benefits
The study incorporated a crossover design from week 9 to week 18, where PANZYGA group participants received placebo and placebo participants received PANZYGA. Researchers observed that mean total CY-BOCS scores continued to improve in both treatment arms. Notably, the improvement was more prominent in participants who initially received PANZYGA until week 9, which researchers attributed to a continued response to the PANZYGA treatment from the first half of the study.
Study Design and Patient Population
The prospective, randomized, double-blind, parallel group, placebo-controlled superiority study enrolled 71 patients aged 6 to 17 with confirmed moderate to severe PANS diagnosis. Participants received three infusions of PANZYGA or placebo over two days every three weeks for nine weeks, followed by an additional double-blind crossover phase of equal duration.
The study was conducted across approximately 30 sites and utilized a two-stage adaptive design with one interim analysis performed by an independent statistician after 40 patients completed the first nine-week treatment period.
Understanding PANS and Treatment Challenges
PANS is diagnosed in children who experience sudden dramatic, often overnight, onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms. According to the National Institutes of Health (NIH), brain inflammation can occur when the body's immune system mistakenly attacks healthy brain cells.
"PANS has been a very challenging disease to treat," said Michael Daines, M.D. "It is very hard on families to see their children afflicted with sudden onset, debilitating, and difficult to treat OCD as well as other cognitive and behavioral issues. These changes impact the ability of children to function in school and at home."
Clinical Significance and Future Directions
Dr. Daines emphasized that the CGI reflects the holistic impact of PANS on a patient's life, encompassing behavioral, cognitive, and physical symptoms. "These results suggest that PANZYGA may address the broader disease burden in pediatric acute-onset neuropsychiatric syndromes, offering a potential therapeutic pathway for families navigating this complex condition. Further research into this investigational use of PANZYGA is needed to confirm this suggestion."
"PANS is a very challenging disease for the medical community and families," said Octapharma USA President Flemming Nielsen. "Parents are confronted with the challenge of seeing their children afflicted with sudden-onset, debilitating, and difficult to treat OCD as well as other behavioral and cognitive issues. Octapharma looks forward to bringing relief to children and their families."
The PACE Foundation, which supported recruitment for the trial, expressed gratitude for Octapharma's commitment. "We're grateful to Octapharma for their compassion and ongoing commitment to families affected by this challenging disease," said Paul Ryan, PACE Foundation Co-Founder and President.
