STOCKHOLM. Umecrine Cognition AB, a Karolinska Development (Nasdaq Stockholm: KDEV) portfolio company focused on developing a new class of neurosteroid based drugs for CNS disorders, today announced positive data based on prespecified analyses of additional endpoint data from a phase 2a study of the safety, pharmacokinetics and exploratory efficacy of golexanolone (formerly GR3027) in patients with cirrhosis and evidence of mild cognitive impairment consistent with hepatic encephalopathy.
These complementary prespecified endpoint data build upon the company’s topline data from the UCAB-CT-02 study announced in April 2020, demonstrating favorable safety and tolerability profile of golexanolone in patients with liver cirrhosis and mild hepatic encephalopathy. Following three weeks of treatment with 10mg, 40mg or 80mg of golexanolone or placebo administered twice daily, subjects in all groups showed directionally favorable, non-significant changes in cognitive function assessed by CRT (continuous reaction time), PHES (psychometric hepatic encephalopathy scores) and ANT (animal naming test) with no difference between golexanlone and placebo. In addition to CRT, PHES and ANT, Epworth Sleepiness Scale (ESS; a commonly used self-assessment measure of sleepiness) and spectral EEG (MDF [mean dominant frequency] and DT/AB [the ratio of the relative powers of slow delta and theta frequencies to relative powers of fast alpha and beta frequencies]) were measured at baseline, 10 and 21 days and are the subject of this release. EEG abnormalities are a recognised accompaniment of covert/minimal HE1.
The additional study data confirmed that golexanolone exhibited a favorable safety and tolerability profile. AE’s (serious events), including SAE’s (serious adverse events) in one patient in the 80 mg group, were consistent with the patient population. As compared with placebo, golexanolone was associated with directionally favorable changes in ESS (p=0.047), and the EEG parameters, MDF (p=0.142) and ratio of DT/AB (p=0.021).
“Covert HE is a complex neurocognitive disease assessed using several different measures of cognitive domains”, said Magnus Doverskog, CEO of Umecrine Cognition. “While we remain disappointed not to have been able to document significant effects on cognition with CRT, PHES, and ANT in this small pilot study, we are excited about the clinical implications of our complementary findings with the subjective and objective measures; i.e., ESS and EEG, respectively. “The findings are consistent with a role for neurosteroids in the cognitive abnormalities characteristic of HE as well as a role for golexanolone in treatment of neurosteroid-mediated cognitive and vigilance disorders, and they are in line with those observed following a single oral dose in healthy adults following allopregnanolone challenge” 2.
For further information, please contact:
Magnus Doverskog, CEO, Umecrine Cognition AB
Phone: +46 (0)73 039 20 52, e-mail: [email protected]
TO THE EDITORS
About Umecrine Cognition AB
Umecrine Cognition, a Karolinska Development (Nasdaq Stockholm: KDEV) portfolio company, is developing a potential therapy that represents a new target class relevant for several major CNS-related disorders. For more information, please visit www.umecrinecognition.com.
References
1. Amodio, P., et al., 1999. Spectral versus visual EEG analysis in mild hepatic encephalopathy. Clin. Neurophysiol., 110; 1334-1344.
2. Johansson, M., et.al., 2018. GR3027 reversal of neurosteroid-induced, GABA-A receptor-mediated inhibition of human brain function: an allopregnanolone challenge study. Psychopharmacol., 235: 1533-43.