BJP publishes data from ESTEVE's E-52862 preclinical studies on pain

ESTEVE announces the recent publication in the British Journal of Pharmacology of important preclinical data that furthers understanding of its highly potent and selective, once-daily, S1R antagonist E-52862, developed by the ESTEVE Research and Development (R&D) team.

José Miguel Vela, PhD, responsible for ESTEVE Drug Discovery and Preclinical Development, stated, "These data demonstrate the role of ESTEVE's E-52862, a NCE from our programme of sigma-1 receptor antagonists, as a novel modulator of pain sensitisation and relief.  It also highlights that the target of this new compound, the sigma-1 receptor, is correlated mechanistically with the compound's ability to relieve pain."

Key data reported in the publication highlight the pharmacological activity of the selective S1R antagonist E-52862, which acts on the central nervous system (CNS) in various preclinical models of pain.  Importantly, the data show E-52862's highly targeted mode of action (MOA) acts specifically on the S1R in relation to pain models evaluated, meaning normal perception and sensations remain unaffected.  In addition, not only was pain relief sustained with repeated administration of E-52862, but in specific models, some improvement was observed over time; likely due to the MOA of E-52862 and not to changes in concentrations of E-52862 in plasma and brain, which were similar after single and repeated E-52862 administration.

A close correlation was observed between the extent that E-52862 was able to enter the brain and bind with the S1R in the CNS and the level of pain relief exerted by E-52862.  In studies of CNS excitability, E-52862 significantly reduced the amplification of the message (hyperexcitability) coming from pain sensors, without affecting non-pain fibers that transmit other types of sensory stimuli.

The S1R also modulates another receptor - mu-opioid - and affects its activity.  As a result, E-52862 may enhance the pain relief effects of opioids (potentiation of opioid analgesia) without increasing opioid-related side effects.

The Phase I programme with E-52862 is complete and included more than 300 subjects (more than 250 received E-52862).  Results from the programme show good safety, tolerability, pharmacodynamic and pharmacokinetic profiles at all doses of E-52862 tested.

Today, ESTEVE's E-52862 clinical programme focuses on pain management - highlighting both neuropathic pain and the potentiation of opioid analgesia.  The Phase II clinical trial programme for E-52862 started in early 2012.

E-52862, whose MOA is both novel and complementary to that of other pain medications, could provide a much-needed addition to future pain management choices with, perhaps, the option to be used as monotherapy, as well as in combination with other pain relief compounds, depending on the type of patient and clinical indication.