Ziconotide (Elan Pharmaceuticals).

Elan Pharmaceuticals (formerly Neurex) is developing ziconotide, a neuron-specific N-type calcium channel blocker, for the potential treatment of severe pain and ischemia. A US NDA for the use of the compound in intractable pain is under review [351606,357600] and phase III trials for ischemia are ongoing [261455,292579]. Elan received an approvable letter from the FDA for pain in June 2000, and by October 2000, was responding to questions raised by the FDA in the letter [372580,386279]. In December 2000, DRAXIS filed an NDS for ziconotide with the Therapeutic Products Programme of Health Canada [393773]. The drug has Priority Review status in Canada [387218]. PAIN: In pivotal studies, ziconotide showed a significant reduction in pain compared to placebo. In the two trials, completed by December 1999, more than 700 patients received the drug for the treatment of intractable pain intrathecally. This included patients who had failed morphine therapy, or who had become intolerant of therapy due to side-effects. The drug was safe and well tolerated over periods as long as 3 years [351606]. ISCHEMIA: Elan and Pfizer (formerly Warner-Lambert) are also developing ziconotide for the treatment of ischemia associated with head trauma and stroke [292579]. In September 1997, Neurex and Warner-Lambert restarted a pivotal phase III head trauma study with no changes in the study design. In July 1997, patient enrollment had been halted pending analysis of clinical data from earlier studies to determine the relative risk/benefits of administering ziconotide with the current protocol [261455]. By April 1999, Parke-Davis (now Pfizer) was also working on the development of nonpeptide analogs of ziconotide, with the aim of developing an orally available agent for the treatment of chronic pain [325613,324954]. In July 2000, Merrill Lynch predicted FDA approval and launch in the third or fourth quarter of 2000 [375966], but in January 2001, the prediction of approval was revised to be in 2001 [395423].