Marinus Pharmaceuticals reported that its Phase III RAISE trial of IV ganaxolone for status epilepticus will be delayed, thanks to the pandemic.
Radnor, Pennsylvania.-based Marinus Pharmaceuticals reported that its Phase III RAISE trial of IV ganaxolone for status epilepticus will be delayed and not completed until the second half of 2023.
The company cited the impact of the Omicron variant on hospital resources and an unexpected interruption of its clinical supply material related to IV ganaxolone. Early in the pandemic, numerous clinical trials were delayed or shifted to a decentralized “virtual” or hybrid format because clinics and hospitals were closed to non-urgent care.
The company temporarily paused the RAISE trial when it found it had to decrease the shelf life of its drug to meet product-stability testing specifications. As a result, it needed to resupply the clinical material, which is taking time, likely until the end of the second quarter. Marinus also said it was implementing improvements in its manufacturing processes to hit a 24-month or greater product shelf life for IV ganaxolone.
For the most part, clinical trials have resumed regular activity, even with trends toward decentralized or hybrid clinical trials that utilize, if appropriate, telehealth, remote monitors, apps and at-home visits. However, much of the RAISE trial is being run in intensive care units, overwhelmed by the recent Omicron variant surge. Both Phase III RAISE trial and the Phase II RESET trial of adjuvant use of ganaxolone in established status epilepticus are expected to be delayed by about six months.
Ganaxolone is a positive allosteric modulator of GABAA receptors. It acts on well-known targets in the brain that have anti-seizure, antidepressant and anti-anxiety effects. It is being developed in both IV and oral formulations.
According to Johns Hopkins Medicine, status epilepticus is defined as a seizure that lasts longer than five minutes or more than one seizure within a five-minute period without returning to an average level of consciousness between seizures.
Marinus indicated that its supply chain interruption affected the IV formulation of ganaxolone and the IV clinical trials, but not the oral suspension formulation or its New Drug Application (NDA) submitted in July 2021 to the U.S. Food and Drug Administration. The NDA is for seizures from CDKL5 deficiency disorder, a rare, genetic form of epilepsy. The target action date for the NDA is March 20, 2022.
As of March 2021, the pandemic had disrupted more than 1,200 clinical trials. In a February 2021 report by GlobalData, disrupted trials had been slowing since June 2020 but leveled off in October 2020. Most of those impacts were related to slow enrollment rather than specific supply chain issues.
Not all diseases or clinical trials are appropriate for a decentralized or hybrid clinical trial design. Some require face-to-face interactions between participants and physicians, while some require complex procedures and specialized efficacy and safety assessments. Studies have suggested at least a threefold increase in remote patient interactions as a response to the COVID-19 pandemic, and “patient-centricity” is an increasingly important concept in clinical trials, making the studies as convenient and easy as possible for the participants.
