E-therapeutics Regulatory News (ETX)

e-Therapeutics plc('e-Therapeutics' or the 'Company')

e-Therapeutics reports top-line Phase IIb results in major depressive disorder

15 February 2016: e-Therapeutics plc (AIM: ETX), the drug discovery and development company, reports top-line results for its phase IIb trial of ETS6103 in major depressive disorder, evaluating its antidepressant activity and tolerance profile.

The trial evaluated dosing of ETS6103 as a potential second-line therapy for patients with major depressive disorder who do not respond satisfactorily or relapse when using the current first-line treatment, selective serotonin reuptake inhibitor (SSRI). The trial's aims were specially to determine whether ETS6103 is an antidepressant capable of treating the patients for whom SSRI treatment has not been successful, at a dose consistent with both improved compliance and a protectable position, with a more benign side effect and tolerance profile than a tricyclic, such as amitriptyline. The earlier Phase IIa trial had shown a surprisingly strong efficacy position for ETS6103 with respect to amitriptyline, and the Phase IIb trial was structured as a non-inferiority study.

The randomised, double-blind non-inferiority study was conducted in Glasgow on behalf of e-Therapeutics. The study enrolled a total of 383 patients into the trial. 164 patients who did not respond adequately to the first-line SSRI treatment were then randomised into one of three study arms which included two doses of ETS6103 and one of amitriptyline. Patients were dosed over an eight-week treatment period.

As regards efficacy alone, the ETS6103 arms did not meet the primary endpoint of establishing non-inferiority when compared to amitriptyline. Specifically, while many patients responded to ETS6103, fewer achieved remission (as defined in the protocol: MADRS score* below 11) than on amitriptyline. Responses were, however, observed in all three experimental arms of the study. In the two ETS6103 arms, some patients went into remission and there were fewer adverse event and side effect dropouts in the ETS6103 groups compared to amitriptyline.

We have previously indicated that if the trial was successful that we would look to out-licence ETS6103. Our initial conclusion is that, while ETS6103, in common with almost all other antidepressants, was not non-inferior to amitriptyline in efficacy terms, the results overall are pleasingly similar to the profile of ETS6103 that we hoped to have. Further analysis of the data is being undertaken and a fuller update will be provided at the preliminary results, due in March.

Commenting on the news, Steve Self, e-Therapeutics' Development Director, said: "The global antidepressant market is substantial and growing and there is an increasing need for effective and less toxic drugs. ETS6103's profile may offer benefit to patients who have not successfully responded to an SSRI and it may have fewer side-effects and superior tolerance when compared to a tricyclic antidepressant. We will analyse the datasets further, particularly in relation to these apparent benefits, to identify what further development and potential out licensing steps should be taken."

* The Montgomery-Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression.

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About e-Therapeutics plc

e-Therapeutics (AIM: ETX) is a drug discovery and development company with a proprietary discovery platform based on advances in network pharmacology and chemical biology.

The Company is applying its platform to the discovery of new drug candidates. The therapeutic focus of the Company's discovery activity is in immuno-oncology and addressing drug resistance in targeted cancer therapies. The platform is yielding multiple, highly potent, selective and diverse molecules at much higher yields than is reported for conventional drug discovery. 

e-Therapeutics is also advancing its most promising programmes through clinical trials. There is a phase IIb clinical stage drug candidate for major depressive disorder, ETS6103; and a phase Ib clinical stage candidate in hepatocellular and pancreatic cancer, ETS2101. The Company also has a variety of preclinical stage assets, including ETX1153c, a functionally resistance-less antibiotic; ETS2300, telomerase inhibition in anti-cancer; ETS3100, small molecule anti-TNFα; and ETS2400 Hedgehog pathway inhibition.

The Company is fully funded to advance its existing development programmes in cancer and depression and a further programme from its discovery platform. It is based at sites in Oxford and Newcastle, UK. For more information about the Company, please visit www.etherapeutics.co.uk