Oryzon Genomics will seek the FDA’s advice after a psychiatric drug failed to impact the symptoms or severity of borderline personality disorder, but executives are keen to push forward with refreshed clinical endpoints.
Vafidemstat was being tested in the phase 2b PORTICO clinical trial among patients with borderline personality disorder. The treatment did not spur an improvement at weeks eight to 12 as measured by the Borderline Personality Disorder Checklist, which measures diagnostic criteria such as instability, recurrent suicidal behavior, gestures, threats or self-mutilating behavior, according to a Friday press release.
Oryzon claimed a win on the secondary endpoint of disorder severity across the same time span using a scale called Borderline Evaluation of Severity that similarly measures symptom severity and adaptive coping responses including negative behaviors, such as self-harm and suicidal thinking. The biotech said that reduction in the treated group was consistent throughout, reaching a maximum of 38% at week 10, compared to placebo.
A statistically significant improvement in agitation and aggression was also seen, reaching a maximum of 80% at week 10, according to the release.
Oryzon said that “all results favored vafidemstat treatment over placebo across the multiple independent primary and secondary efficacy endpoints.”
“Although we have not met the primary endpoints of the study, we still consider the trial results to be very positive and promising,” said CEO Carlos Buesa. “This is the first time, to the best of our knowledge, that a large, randomized phase 2 trial in BPD had two secondary endpoints that met statistical significance reflecting clinically meaningful improvements in overall BPD severity and in agitation/aggression.”
Vafidemstat was safe and well-tolerated, with safety results similar to the drug’s known profile. Treatment-emergent adverse events were slightly lower in the treatment arm at 57.5% compared to 65.4% in the placebo group. Discontinuations were low overall, Oryzon said.
“The results provide support and a path forward for vafidemstat’s future clinical development as a potentially promising treatment for overall BPD disease and agitation and aggression,” Chief Medical Officer Michael Ropacki, M.D., said in a statement.
The company is committed to further developing vafidemstat and will request a meeting with the FDA to determine next steps. The goal is to move forward into a phase 3 trial with slightly different endpoints based on the phase 2 results, CEO Buesa said.
“In a disease with no ‘gold standard’ measure, PORTICO achieved an important milestone by helping determine what endpoints should be carried forward, as well as establishing the effect size needed to design a well-powered future phase 3 BPD clinical trial,” Ropacki said.
Vafidemstat is also being tested in schizophrenia and was previously tested for complications of COVID-19, aggressiveness in Alzheimer’s disease and multiple sclerosis. Other clinical programs for the drug include Kabuki Syndrome and other neurodevelopmental syndromes.