The Umeå-based company reports new results from its phase 2a study of GR3027, a drug candidate being developed as a potential new treatment for a range of CNS-related disorders.
The primary study objectives were met in regard to safety and pharmacokinetics. The study also showed preliminary evidence of clinical efficacy in a subset of patients, but the data needs to be further analyzed before a decision to potentially move forward with the development of GR3027 in idiopathic hypersomnia or other sleep disorders. In parallel, Umecrine Cognition will continue the clinical development in hepatic encephalopathy.
GR3027 is a GABAA receptor modulating steroid antagonist (GAMSA) that has previously been shown to improve neurological impairments – including cognitive and sleep alterations – in animal models and mitigate the brain-inhibitory effects of intravenously administered neurosteroid, allopregnanolone, in humans.
The Phase 2a study
The exploratory phase 2a study of GR3027 in patients with idiopathic hypersomnia enrolled 10 patients, including 5 females and 5 males, at Sleep Centers in Finland, Denmark and Sweden. The study consisted of two parts; part one was an open-label trial to assess safety, tolerability and pharmacokinetics (PK) of a single oral 50 mg dose of GR3027 in female patients. Part two was a randomized, double-blind, placebo-controlled crossover study to assess safety, tolerability, and exploratory efficacy of twice daily 80 mg oral doses of GR3027 during two weeks in adult male and female IH patients. Patients were randomized to one of two-treatment sequences, starting with a 2-week treatment with either placebo or GR3027, followed by no treatment for 1 week and finally the alternate 2-week treatment with either GR3027 or placebo. Each patient therefore received either GR3027 or placebo during one of the two treatment periods.
The Maintenance of Wakefulness Test (MWT) and the Epworth sleepiness scale (ESS) were designated as the main exploratory efficacy measures. MWT objectively measures the patients’ ability to stay awake in a controlled setting while ESS is based on patients’ subjective assessment of sleepiness. Additionally, a number of other exploratory measures of efficacy were followed including the actigraphy that objectively record sleep/wake patterns, and some subjective measurements like the Clinician Global Impression of Change (CGIC), Patient Global Impression of Change (PGIC), Karolinska Sleepiness Scale (KSS), Sleep-wake diary and Chalder Fatigue Scale (CFS).
A complex disease
The results showed that the PK characteristics of GR3027 in females are similar to those previously observed in men. The safety profile, which has previously been studied for up to 5 days of multiple ascending doses in adult males, continues to be favorable with no dose-limiting toxicities or serious adverse events (SAEs) in either males or females. The results of the ability to stay awake, as determined by the objective measurement MWT, showed a favorable trend (p = 0.098). The drug candidate GR3027 had little effect on the subjective measurement ESS (p = 0.92). As expected in a small exploratory study, none of the results were statistically significant. A subgroup of 5 out of 10 subjects exhibited directionally favorable changes in 3 or more efficacy measures.
“We are pleased by the excellent safety profile of GR3027 in patients with idiopathic hypersomnia. It is also encouraging that we, already in this comparatively short and small Phase 2a study, were able to see indications of clinical benefit. Idiopathic hypersomnia is a complex disease with a heterogenic patient population, as demonstrated by the lack of approved treatments. We will therefore further analyze the results and evaluate the need for complementary studies to properly identify the right patient population before potentially proceeding with a larger trial. In parallel, the clinical development of GR3027 in hepatic encephalopathy continues, with Phase 2-data expected early 2020,” comments Magnus Doverskog, CEO, Umecrine Cognition.
Photo of Magnus Doverskog, CEO, Umecrine Cognition