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ESTEVE Announces Publication of Key Preclinical Data for a Novel Oral, First-in-class New Chemical Entity (NCE) Sigma-1 Receptor Antagonist (E-52862), that has Completed Phase I and Initiated its Phase II Clinical Trial Program

BARCELONA, July 17, 2012 /PRNewswire/ --

  • The sigma-1 receptor (S1R) is an important development target for innovative medications to treat neuropathic pain, for which new medications are much needed.
  • Developed by ESTEVE, E-52862 is a potent, highly selective NCE with a novel mechanism of action (S1R antagonism) currently being evaluated for the treatment of pain.
  • In studies conducted to date in preclinical models, a direct relationship between dose of E-52862, levels of E-52862 interacting with the S1R in the brain, and analgesic activity (pain-relieving effect) was demonstrated.
  • Importantly, in these models, the pain-relieving effect of E-52862 is maintained with repeated treatment.
  • E-52862 has completed a rigorous Phase I programme that included more than 300 subjects.  Results show good safety, tolerability, pharmacodynamic and pharmacokinetic profiles.
  • Phase II clinical trials evaluating E-52862 are ongoing.

ESTEVE announces the recent publication in the British Journal of Pharmacology[1] 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.


ESTEVE is a leading pharmaceutical chemical group based on Barcelona (Spain) with significant international presence.  Since it was founded in 1929, ESTEVE has been firmly committed to excellence in healthcare, dedicating its efforts to innovative R&D of new medicines for unmet medical needs and focusing on high science and credible, evidence-based research.  ESTEVE has a strong partnership approach to drug discovery, development and commercialisation.  The company works both independently and in collaboration to bring new, differentiated best-in-class treatments to patients who need them. ESTEVE currently has a team of about 2800 professionals, and has subsidiaries and production facilities in several European countries, USA, China and Mexico.

About E-52862 and Pain R&D at ESTEVE

ESTEVE's dedicated in-house R&D team is focused on the development of novel pain medications, an area of high unmet medical need.  Considerable progress in the knowledge of the biology and pharmacology of the S1R (a unique protein) during the last few years has re-energised research into the potential benefits of S1R ligands in a range of neurological and psychiatric conditions.

New data has addressed key questions on modulation, MOA and pathophysiology of the S1R.  The proprietary ESTEVE S1R knockout mouse demonstrated a direct role of the S1R in sensitisation phenomena associated with neuropathic pain mechanisms and behaviours.  E-52862 induces robust, dose-dependent analgesic activity in multiple preclinical neuropathic pain models.  E-52862 could have potential applications for other neurological and psychiatric indications.  Besides information reported here, an extensive preclinical regulatory safety package is available for E-52862 (including 13-week repeat dose toxicity studies in rats, dogs and monkeys).  E-52862 also has robust intellectual property protection.

ESTEVE's portfolio in pain also includes a technology platform-derived new co-crystal entity (E-58425) developed by the in-house R&D team at ESTEVE.  E-58425 has completed Phase I, with Phase II currently ongoing.  E-58425 is being developed for moderate to severe acute and chronic pain.


[1] Romero L et al.  Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitisation.  Br J Pharmacol 2012 Mar 9 [Epub ahead of print]. doi: 10.1111/j.1476-5381.2012.01942.x.

For more information and enquiries into partnership opportunities, please contact:

Mark Mayhew, PhD, Head of ESTEVE R&D Strategic Partnering, Tel. +34-93-446-6000,

For corporate communications/media enquiries, please contact:

Ma. Ángels Valls, Head of ESTEVE Corporate Communications, Tel. +34-93-446-6000,

Visit our new R&D website:

Follow us on Twitter: @ESTEVE_news

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