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Merck and Neuromed feel the pain

By Dr Matt Wilkinson , 09-Aug-2007

Merck & Co's latest bid to fill the gap left by the withdrawal of Vioxx (rofecoxib) has hit another stumbling block as it has dropped NMED-160 that it was developing in collaboration with Neuromed.

NMED-160 (also known as MK-6721) is an orally available N-type calcium channel blocker that was in Phase II trials for the treatment of chronic pain and was pulled out of development after the firms decided it "did not demonstrate the ideal pharmaceutical characteristics considered necessary to advance the compound further into development".


Interestingly, no adverse effects were observed during the trials even when does of up to 1,600mg were administered.


"We are encouraged by what we have learned from MK-6721 and are continuing our productive collaboration with Merck with a focus on improving the pharmaceutical properties of our compounds to produce a best-in-class pain treatment," said Dr Christopher Gallen, CEO of Neuromed.


"We believe the N-type calcium channel is an important target for the development of new pain treatments and our studies to date support that. Our collaboration with Merck has resulted in the discovery of additional N-type calcium channel blockers that we continue to advance towards clinical trials."


Calcium channels control the entry of calcium into neurons, opening up to allow calcium into the cell on receiving a pain signal.


This leads to the release of neurotransmitters from synaptic vesicles which lead to the brain perceiving pain.


Calcium channels are involved in a variety of other signalling pathways, so the selective blocking of the specific channels that are responsible for pain signal transmission is important.


N-type calcium channel blockers are a novel class of analgesics that only block those channels involved with pain signal transmission.


Calcium-channel blockers became a target of interest at the end of last year with the approval of Elan Pharmaceutical's Ziconotide (PRIALT), a peptide that blocks the Cav(2.2) N-type channel.


However, Ziconotide needs to be administered by intrathecal injection directly into the spinal cord limiting the commercial use of the drug.


NMED-160 would have been the first orally available drug to target these channels and would have no doubt boosted the company after the hit its finances took after the withdrawal of Vioxx, which was once a $2.5bn drug.


The deal between Merck and Neuromed was valued at $475m, but this figure may be reduced dramatically if none of the other compounds developed during the collaboration make it into trials.


However the set back does not appear to have put off either company with Dr Darryle Schoepp, senior vice president of Neuroscience at Merck saying that companies were committed to further research and development of oral N-type calcium channel blockers for pain and that they were "pleased with the results of our ongoing collaboration".

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