West Coast Editor
Merck & Co. Inc.'s decision to back away from the Phase II-stage, N-type calcium channel blocker NMED-160 for pain leaves intact its collaboration with privately held Neuromed Pharmaceuticals Inc., and the companies plan to keep working in the same pathway to find another compound.
Orally delivered NMED-160 (also known as MK-6721) failed to "demonstrate the ideal pharmaceutical characteristics" for advancing, the firms said in a press release, though researchers saw no adverse events in single doses of up to 1,600 mg.
The drug did not reach clinical trials in chronic pain, said Christopher Gallen, president and CEO of Vancouver, British Columbia-based Neuromed, so efficacy has yet to be proved, and the companies want to be certain they have just the right properties before pushing a molecule that far.
"Welcome to biotech," Gallen said. "Sometimes it's the first molecule; sometimes it's the second or third."
On signing their potential $475 million deal in the spring of 2006, Merck, of Whitehouse Station, N.J., and Neuromed said they hoped to target with NMED-160 the pain of inflammatory conditions, such as osteoarthritis, or neuropathic ailments, such as diabetic neuropathy.
Early work suggested the drug was as effective as morphine but without the side effects, and could be useful in chronic pain. (See BioWorld Today, March 21, 2006.)
"It's hard to give a time line" for next steps, Gallen said. "We're pretty comfortable with the safety profile we observed with the initial molecule, we've had an active research collaboration going on for the past year, and obviously we were working on the chemistry before that."
Most of the money lay at the back end of the Merck deal, with success in launching NMED-160 for an initial single indication on a worldwide basis triggering milestone payments totaling $202 million, a number that would increase to about $450 million if a further indication for NMED-160 were developed and approved, and if another compound were developed and approved for two indications.
More milestone payments would be paid if other compounds were developed.
Though approved calcium channel blockers of the L-type are well known for treating cardiovascular conditions, calcium channels also control the entry of calcium into the neuron, which triggers neurotransmitters and results in a pain signal.
Dublin, Ireland-based Elan Corp. plc, with its marketed Prialt (ziconotide) - the synthetic equivalent of a naturally occurring conopeptide found in a marine snail - has proved that hitting the N-type channels works. But Prialt is given by intrathecal infusion for severe chronic pain. The compound is administered directly into the spinal column by an implanted pump.
"As a biologic, it's commercially very limited," Gallen said.
Neuromed also is working on T-type calcium channel blockers, which act in yet a different way, and compounds in that class might be useful for acute and chronic pain.
"Those efforts are quite advanced," Gallen said. "We're expecting to move forward into man over the next year to 18 months. In the meantime, clinical and commercial groups are gearing up to handle OROS Hydromorphone," licensed earlier this year in the U.S. for $30 million from Johnson & Johnson subsidiary ALZA Corp. (See BioWorld Today, April 25, 2007.)
Hydromorphone is a widely available Schedule II opioid analgesic. Standard versions require dosing several times per day, but OROS is a once-daily formulation 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.
"Right now, we're designing the clinical trials and working through the initial activities," with a plan to talk with the FDA about a special protocol assessment, Gallen said.