Success for EIP Pharma’s two Phase 2a Alzheimer’s Disease clinical trials
Posted: 13 December 2016 | | No comments yet
The results of two recently completed Phase 2a clinical trials that demonstrated significant Alzheimer’s disease relevant pharmacological activity…
EIP Pharma has obtained proof-of-mechanism for neflamapimod (VX-745), with the results of two recently completed Phase 2a clinical trials that demonstrated significant Alzheimer’s disease relevant pharmacological activity.
Each trial was conducted in patients with Mild Cognitive Impairment due to Alzheimer’s disease, or mild Alzheimer’s disease.
Major efficacy findings from the clinical phase 2a studies are as follows:
- Statistically significant improvement in tests of episodic memory and learning; as assessed by Wechsler Memory Scale (WMS) immediate and delayed recall composite measures in Study 302, and Hopkins Verbal Learning Test – Revised (HVLT-R) in Study 303
- Reductions in brain amyloid plaque load, as assessed in Study 302 by quantitative dynamic amyloid PET scan
- Definition of 40 mg twice daily as the optimal dose for neflamapimod in the treatment of Alzheimer’s disease
In addition, neflamapimod at a dose level up to 125 mg twice daily for 12 weeks was very well tolerated in patients with Alzheimer’s disease, and neflamapimod was confirmed to be blood-brain-barrier penetrant in humans.
“Neflamapimod treatment showed improvement in memory tests that assess immediate and delayed recall in both Phase 2a studies, strongly suggestive of reversal of synaptic dysfunction. In addition, in our study, 12 weeks treatment at a 40 mg dose level led to a reduction in brain amyloid plaque load, as assessed by dynamic PET scanning,” said Professor Philip Scheltens, VU Medical Center in Amsterdam.
Biomarker and Cognitive Results
Study 302 (12-week treatment)
Amyloid PET: 40 mg dose level showed lowering of quantitatively measured brain amyloid plaque load with 12 weeks of neflamapimod treatment: 3 of 8 patients demonstrated greater than the pre-specified response criteria of 7% reduction (-11.6%, -11.9% and -40% in PET signal, respectively, for the 3 responder patients) and 2 patients were between 3 and 7% reduction. In addition, one patient at 125 mg with plasma drug concentration equal to that of 40mg also met the response criteria (-7.1%).
Cognition: Mean Wechsler Memory Scale (WMS) immediate recall composite scores increased from 48.4 (+/- 3.8) at baseline to 58.4 (+/-4.3) at Day 84 (n=15; p=0.005 by wilcoxen sign rank test for improvement). Mean WMS delayed recall composite scores increased from 13.2 (+/- 2.3) at baseline to 22.1 (+/- 4.1) at Day 84 (p<0.001). Seven of 8 patients in 40 mg group and 6 of 7 in 125 mg group showed improvement from baseline in immediate recall composite score; 8 of 8 patients in 40 mg group and 6 of 7 in 125 mg group showed improvement from baseline in delayed recall composite score. Median change in MMSE scores from baseline to Day 84 was +1.5 in the 40 mg group and 0.0 in the 125 mg group.
Study 303 (6-weeek treatment)
Cognition: Mean Hopkins Verbal Learning Test – Revised (HLVT-R) Total Recall improved from 19.1 (+/-1.5) at Baseline to 22.6 (+/-2.1) at week 6 (p=0.029 vs. Baseline; p=0.015 for improvement); Delayed Recall increased from 5.4 (+/-0.6) to 7.5 (+/-1.1) (p=0.055; p=0.028 for improvement). Median increase in Total Recall score was 4.5 (range: -2.5 to +9.5), with only one subject with a decrease during treatment. MMSE scores improved by mean of 0.5 (+/-0.7) and median of 1.0 point.
Cytokines: Of nine cytokines assessed, only CSF IL-8 quantifiable at all time points. CSF IL-8 at week 6 was significantly reduced compared to Baseline (p<0.001) in the three subjects who had the highest plasma drug levels.
CSF amyloid beta: A concentration dependent trend was seen: the three subjects with the highest plasma drug exposure had higher levels of Aβ peptides at week 6 compared to Baseline; while the remaining subjects had similar or lower levels of Aβ peptides at week 6 compared to Baseline.