Edge Therapeutics Reports Positive Top-Line Phase I/II NEWTON Trial Results


Edge Therapeutics, Inc. recently announced that its recently completed North American Phase I/II NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) trial has met its primary and secondary endpoints of safety, tolerability, maximum tolerated dose (MTD), and pharmacokinetics of a single intraventricular injection of EG-1962. EG-1962, the company’s lead product candidate, is in development to treat patients who have suffered an aneurysmal subarachnoid hemorrhage (aSAH) resulting from a ruptured brain aneurysm.

The NEWTON trial evaluated six dose-cohorts (100, 200, 400, 600, 800, and 1200 mg). The primary endpoint was to establish the maximum tolerated dose, which has been determined to be 800 mg. Safety and tolerability data are available for all six cohorts, while EG-1962 efficacy results are reported for only five cohorts, as the sixth cohort (1200 mg) was not a tolerable dose. Safety results show that no patients (0 of 54) experienced EG-1962-related hypotension, while 17% of patients (3 of 18) treated with oral nimodipine, the current standard of care, experienced drug-related hypotension.
The secondary endpoint of characterizing the pharmacokinetics of EG-1962 was also met. The steady-state plasma concentration measured in patients treated with EG-1962 in the NEWTON trial were below 30 ng/ml, the level of plasma concentrations observed to cause systemic hypotension.

Exploratory endpoints measuring outcome results from the 90-day follow-up available demonstrated that 60% (27 of 45) of patients treated with EG-1962 experienced a favorable outcome (a score of 6-8) as measured by the extended Glasgow Outcomes Scale (GOSE). By contrast, the 90-day favorable outcome rate for patients treated with the current standard of care, oral nimodipine, was only 28% (5 of 18). (The GOSE is a clinically validated 8-point scale (1 = death, 8 = good recovery) used to assess recovery for patients who have suffered a ruptured aneurysm. A favorable outcome in the NEWTON trial protocol is defined as a GOSE score of 6 or greater as measured 90 days after aSAH.) In addition, improved efficacy was supported by a reduction in vasospasm, delayed cerebral ischemia and use of rescue therapies.

EG-1962 is a novel polymeric nimodipine microparticle containing nimodipine suspended in a diluent of hyaluronic acid that utilizes the Company’s proprietary PrecisaTM development platform designed to improve patient outcomes following aSAH. EG-1962 has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with aSAH.

An aneurysmal subarachnoid hemorrhage, or aSAH, is a brain hemorrhage after which blood from a ruptured aneurysm enters the subarachnoid space, the area between the middle and deepest protective layers of the brain. Approximately 600,000 individuals worldwide suffer an aSAH annually. In the US, approximately 35,000 aSAH patients, with an average age of 52, arrive alive at the hospital each year, and approximately 75% of these patients die or suffer permanent brain damage.

The NEWTON trial is a multicenter, randomized, controlled, open-label Phase I/II trial evaluating the safety, tolerability and pharmacokinetics of escalating doses of EG-1962 compared to the current standard of care, oral nimodipine, in subjects with aSAH. Of the total of 72 patients enrolled, 54 patients were randomized to receive EG-1962 and 18 patients were randomized to receive oral nimodipine.

EG-1962 and EG-1964 both utilize the company’s proprietary, programmable, biodegradable polymer-based development platform, known as Precisa. The Precisa platform allows the company to create therapeutics capable of delivering medicines directly to the site of injury, providing a novel delivery mechanism that enables targeted and sustained drug exposure while potentially avoiding the systemic, dose-limiting side effects often associated with current standards of care.

Edge Therapeutics is a clinical-stage biotechnology company that discovers, develops and seeks to commercialize novel, hospital-based therapies capable of transforming treatment paradigms in the management of acute, life-threatening conditions. EG-1962, our lead product candidate, has the potential to fundamentally improve patient outcomes and transform the management of aneurysmal subarachnoid hemorrhage, or aSAH, which is bleeding around the brain due to a ruptured brain aneurysm. EG-1964, our second product candidate, is being evaluated as a potential prophylactic treatment in the management of chronic subdural hematoma, to prevent recurrent bleeding on the surface of the brain. For more information, visit www.edgetherapeutics.com.

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