Staff Writer

Putting together a new drug application for the extended-release pain drug Exalgo (hydromorphone), Neuromed Pharmaceuticals Inc. found out its longstanding deal with Merck & Co. Inc. for the same indication has fallen apart.

Merck said none of the compounds generated in the collaboration met the profile necessary to advance them.

Vancouver, British Columbia-based Neuromed entered the pact, valued at up to $475 million and centered on N-type calcium channel blockers, in 2006. The lead compound, NMED-160, was in Phase II trials, but fizzled more than a year later, and the partners moved on to others, hoping to find one that fulfilled the promise of the class. (See BioWorld Today, Aug. 9, 2007, and March 21, 2006.)

Approved, L-type calcium channel blockers are famous for treating cardiovascular conditions, but calcium channels - those of the N type - control the entry of calcium into the neuron, too, which triggers neurotransmitters and results in a pain signal. Dublin, Ireland-based Elan Corp. plc sells the N-type calcium channel blocker Prialt (ziconotide), which proves the mechanism of action but is administered directly into the spinal column by an implanted pump.

First envisioned as possibly grabbing as much of the $30 billion pain drug market as triptans or SSRIs, N-type channel blockers numbered three in the program, and the deal garnered $25 million up front from Merck, along with research funding for two years. Merck had an option to renew the deal for an extra two years.

But the larger bolus of hoped-for money was on the deal's back end. Success in launching NMED-160 or one of its alternatives for an initial single indication on a worldwide basis would have triggered milestone payments totaling $202 million. Those payments could have boosted to about $450 million if a further indication had been developed and approved, and if another compound had reached approval.

None of that will happen now, and attention has turned to a more immediate project. In March, privately held Neuromed disclosed positive Phase III data with Exalgo formerly NMED-1077, and once known as OROS Hydromorphone - from Johnson & Johnson subsidiary ALZA Corp., of Mountain View, Calif. The company had better luck with Exalgo, which earlier had failed in Phase III, probably because of the trial design. (See BioWorld Today, April 25, 2007.)

Neuromed's Phase III trial with Exalgo met a primary endpoint agreed upon by way of a special protocol assessment: the mean change from baseline to week 12 (or last visit) of average weekly pain intensity scores.

Hydromorphone is a widely available Schedule II opioid analgesic, but available versions are dosed several times per day, and Exalgo just once.

It's based on ALZA's OROS Push-Pull controlled-release drug delivery system. Janssen-Cilag, another J&J offshoot, markets the drug as Jurnista in Germany and other European countries. Neuromed expects to file the NDA in this quarter.