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,
- 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 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)
Jose 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
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.
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
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
 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,
communications/media enquiries, please contact:
Ma. Angels Valls,
Head of ESTEVE Corporate Communications, Tel. +34-93-446-6000,
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Posted: July 2012