Zalicus in agony after painkiller failure
To lose one drug candidate after disappointing phase II results may be regarded as a misfortune; to lose two looks like carelessness. Just over a year since halting its rheumatoid arthritis project Synavive, Zalicus has ceased development of Z160, the calcium channel blocker for pain that had, post-Synavive, become its lead candidate.
The failure is a blow to research into non-opioid painkillers, but is an even greater one to Zalicus. The company’s share price fell 72% yesterday to $1.30 – just six weeks after it completed a six-for-one reverse split to get its stock price back above Nasdaq's $1 minimum requirement. With just $19m of cash, and a clinical pipeline consisting of another calcium channel blocker, this time in phase I, the outlook is bleak.
Z160, an N-type calcium channel inhibitor, missed the primary endpoints of two phase II studies, one in lumbosacral radiculopathy and another in postherpetic neuralgia. While its safety profile was beyond reproach, it failed to demonstrate a better analgesic effect than placebo.
Flunking in postherpetic neuralgia, for which it had orphan designation, was a particular disaster, as a hit here would have enabled the company to move into larger and more important segments of the neuropathy market.
The failure underscores the near-unassailable position of opioid painkillers as the only drugs reliably capable of treating severe pain. Zalicus had good reason for trying something new, though, as steps are being taken particularly in the US to restrict the availability of abusable drugs.
The company also had some justification for its choice of target: one N-type calcium channel-blocking painkiller, Jazz Pharmaceuticals’ Prialt, has already made it to market. However, this is a peptide – a toxin derived from a cone snail, in fact – and must therefore be administered by injection directly into the spine. It has been shown to provide pain relief in patients who have failed all other therapies, but it is easy to see why sales have never really taken off.
Thus, an oral small-molecule N-type inhibitor could have been quite the money-spinner. But bioavailability has always been a concern with Z160. Zalicus reformulated the agent to improve its absorption profile after its former partner Merck returned rights to the original formulation in 2007, saying it did not have “the ideal pharmaceutical characteristics”.
A different kind
It is therefore clear why Zalicus is emphasising that, while its one remaining compound is also a calcium channel inhibitor, it is a different kind of calcium channel inhibitor.
Z944, a phase I-stage painkiller, blocks T-type calcium channels. Analysts from Piper Jaffray say this target has been validated for epilepsy but somewhat less so for pain. Zalicus says that it is now focusing its efforts on this project, and safety data are expected in late 2013 or early 2014 – already a delay, as it had been expected to enter phase II in mid-2013.
But no matter how close the focus and how great the efforts, Z944 will have to perform extraordinarily well to make up for the loss of the previous two leads. It is surely next to impossible for Zalicus to fund its development very far with what little cash it has.
The Synavive snafu had already left the company vulnerable (Zalicus precarious after loss of Synavive, September 11, 2012). Its future is now hanging by a thread.