Neuren Phase 2 trial shows major improvements in Pitt Hopkins syndrome

Neuren Pharmaceuticals, a biotechnology company based in Melbourne, Australia, has reported encouraging results from its Phase 2 clinical trial of NNZ-2591, a novel therapeutic candidate for Pitt Hopkins Syndrome (PTHS). This trial marks a significant step forward for an underserved patient population with no currently approved treatments.

Trial Design and Participants

The open-label Phase 2 trial involved 16 children aged 3 to 17 years (mean age 9 years) across five hospitals in the United States. The trial aimed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of NNZ-2591 over a 13-week treatment period. Participants received an oral liquid dose of NNZ-2591 twice daily, with dosages escalating in two stages up to a target dose of 12 mg/kg. An initial screening period of at least four weeks was conducted to establish baseline characteristics. The primary endpoints focused on safety and pharmacokinetics, while secondary endpoints included four efficacy measures specifically designed for PTHS, assessed by both clinicians and caregivers.

Safety and Tolerability

NNZ-2591 demonstrated a favorable safety profile and was well tolerated. All Treatment Emergent Adverse Events (TEAEs) were mild to moderate, with no serious adverse events reported. Most TEAEs were unrelated to the study drug. Eleven subjects completed the trial, and the discontinuations were primarily due to TEAEs that resolved over time. There were no significant trends observed in laboratory values, electrocardiograms (ECGs), or other safety parameters.

Efficacy Results

The trial showed statistically significant improvements from baseline in all four efficacy measures specifically designed for PTHS. Using the Wilcoxon signed rank test (p<0.05), the improvements were evident for participants who completed the trial (n=11) and when including those who discontinued (n=15).

Clinicians and caregivers reported meaningful improvements in global efficacy measures:
- Clinical Global Impression of Improvement (CGI-I): 9 out of 11 children showed improvement, with a mean score of 2.6.
- Caregiver Overall Impression of Change (CIC): 8 out of 11 children showed improvement, with a mean score of 3.0.

Additionally, clinically relevant improvements were noted in communication, social interaction, cognition, and motor skills. Improvements were also observed in the Clinical Global Impression of Severity (CGI-S) and the Caregiver Top 3 Concerns overall score, with language and communication being the most frequently noted concerns.

Expert Opinions

Neuren CEO Jon Pilcher expressed optimism about the trial results and emphasized the urgency of addressing the unmet needs of the PTHS community. Dr. Elliott Sherr, an investigator from the University of California San Francisco, highlighted the trial's promising outcomes and the potential of NNZ-2591 for other neurodevelopmental disorders. Dr. Nancy Jones, Neuren's Vice President of Clinical Development, pointed out the importance of syndrome-specific measures for assessing severe neurodevelopmental disorders.

Concluding Remarks

The positive results from this Phase 2 trial of NNZ-2591 strengthen confidence in its potential as a treatment for multiple neurodevelopmental disorders. Neuren Pharmaceuticals plans to continue its efforts in developing the first approved treatment for Pitt Hopkins syndrome, aiming to address a significant unmet medical need in this patient population.

Pitt Hopkins syndrome is a rare neurodevelopmental disorder caused by mutations in the TCF4 gene on chromosome 18. It affects approximately 1 in 34,000 to 1 in 41,000 people and is characterized by developmental delays, intellectual disability, and various behavioral and physiological issues.

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