News: Edge Therapeutics, Inc. (Nasdaq:EDGE) today announced updated results from its ongoing analyses of the Phase 3 NEWTON 2 study of EG-1962 in adults with aneurysmal subarachnoid hemorrhage (aSAH). As previously announced, upon the recommendation of a Data Monitoring Committee (DMC), Edge discontinued the NEWTON 2 study following a pre-specified interim analysis, conducted after 210 patients completed the Day 90 follow-up evaluation, that indicated a low probability of achieving a statistically significant difference compared to standard of care oral nimodipine in the study’s primary endpoint, were the study to be fully enrolled.
The Phase 3 multi-center, randomized, double-blind, placebo-controlled, NEWTON 2 study compared the efficacy and safety of EG-1962 to oral nimodipine in adults with aSAH. The NEWTON 2 study was designed to detect a 15% absolute improvement in favorable outcomes at Day 90 for the EG-1962 treatment group with a target enrollment of 374 subjects. Prior to discontinuation of the study, 283 subjects were randomized and treated. The current analysis includes 266 subjects who completed the Day 90 follow-up evaluation. This analysis showed that in the study’s primary endpoint, 45% (58/129) of subjects treated with a single intraventricular injection of EG-1962 experienced a favorable outcome (a score of 6 to 8 on the extended Glasgow Outcome Scale, or GOSE) at Day 90, compared to 41% (56/137) of subjects treated with oral nimodipine (see Table 1). The GOSE is a clinically validated scale to assess recovery for patients who have suffered a brain injury.
In the NEWTON 2 study, subjects were stratified at randomization by baseline severity as measured by the World Federation of Neurological Surgeons (WFNS) grade. In the pre-specified subgroup of subjects with WFNS grade 3 or 4 (severe aSAH subjects) 43% (29/67) of subjects treated with EG-1962 experienced a favorable outcome as measured by GOSE, compared to 29% (20/70) of subjects treated with oral nimodipine. While these results did not achieve statistical significance (as the NEWTON 2 study was not powered to provide statistical significance for subgroups), they suggest a clinically meaningful potential benefit for EG-1962 in subjects with WFNS grade 3 or 4. Further, these results are consistent with results from Edge’s Phase 1/2 NEWTON study. In that study, EG-1962 demonstrated a similar efficacy trend in favorable outcome rate compared to oral nimodipine in severe aSAH subjects with WFNS grades 3 or 4, with 37% (10/27) of the subjects treated with EG-1962 experiencing a favorable outcome, compared to 23% (3/13) of the subjects treated with oral nimodipine.
In the WFNS grade 2 subgroup (moderate aSAH subjects), favorable outcome rates from the the NEWTON 2 study (see Table 1) were inconsistent with those observed in the Phase 1/2 NEWTON study in both the EG-1962 and oral nimodipine treatment groups. In addition, the favorable response rate in the control group in NEWTON 2 was higher than, and inconsistent with, that reported in the medical literature.
