The lead molecule arising from our Fatty Acid Amide Hydrolase research programme, V158866 completed a phase II study in spinal cord injury patients in August 2015.  It is now available for partnering.


The FAAH enzyme metabolises the endocannabinoids (ECs) which are neurotransmitters acting on a range of different receptors. Inhibit FAAH, and elevated EC levels appear in the nervous system. Amongst the receptors which the ECs act upon are the CB1, CB2 and TRPV1 receptors, stimulation of which has been shown to relieve pain. ECs also act on the PPARα receptor which is known to reduce inflammation.

  • Generated from in-house research programme
  • Potentially profound analgesic response
  • Effective in pre-clinical pain models

FAAH inhibitors

May cause powerful analgesic response

Since endocannabinoids are only produced on demand, it may be that FAAH inhibitors, such as V158866, can selectively increase the local levels of neurotransmitter in tissues. This could deliver a powerful analgesic and anti-inflammatory response, without the side effects that more widespread cannabinoid receptor activation can generate.


Vernalis identified Fatty Acid Amide Hydrolase as a target that might be particularly amenable to our research techniques back in 2007. V158866 was the lead molecule to emerge from this research programme, demonstrating our ability to generate promising candidates that go on to full pipeline development.

Leading players in the pharmaceutical industry are paying particular interest to FAAH inhibitor molecules, with a number of them currently in development by the major companies. Additional possible indications for the class include the treatment of anxiety and depression.

Pre-clinical studies

V158866 has been shown to be a potent and selective slowly reversible inhibitor of human FAAH1 (IC50 24nM). It has been evaluated in a series of pre-clinical pain models and has been shown to have efficacy in:

  • Carageenan-induced thermal hyperalgesia
  • Carageenan-induced inflammation
  • Mono-iodoacetate model of osteoarthritis
  • Chronic constriction injury model of neuropathic pain


It has no significant effect on locomotor function in pre-clinical models, even at high doses.

A range of pre-clinical safety and pharmacokinetic studies were conducted on V158866.

Clinical studies

Positive results were announced in September 2011 for V158866 in a Phase I SAD and MAD study. The double-blind, placebo controlled study investigating single and multiple ascending doses was conducted in healthy male volunteers. The objective of the study, to identify doses of V158866 that are both safe and well tolerated and to measure the compound's effect on FAAH activity and endocannabinoid levels, was achieved. The study has confirmed V158866 is a potent inhibitor of human FAAH and has identified once daily doses to be tested in future studies in pain or other indications.

In August 2015, the Company announced results from a Phase II POC study in which the programme was being investigated in patients with neurophathic pain as a result of spinal cord injury.  Although the dosing of V158866 resulted in elevated endocannabanoid levels, on an intent-to-treat basis, the study failed to meet its pain reduction primary endpoint. Treatment did show a trend towards efficacy on a per protocol basis and was generally well tolerated.

We do not plan to make any further investment in this programme and seek to realise its potential value through partnering.

Project Status

Pre-clinical sudies completed, clinical studies were initiated in March 2011 and the positive results of the Phase I SAD and MAD study announced in September 2011. We initiated a Phase II proof-of-concept study in 2013 and clinical study results were announced in August 2015.

We do not plan to make any further investment in this programme and seek to realise its potential value through partnering

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To report SUSPECTED ADVERSE REACTIONS, contact Vernalis Therapeutics, Inc. at 1-855-705-9546 and drugsafety@propharmagroup.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch