Neurex/Warner-Lambert SNX-111 head injury pivotal trial resumes, with target completion date in two years.

NEUREX SNX-111 HEAD TRAUMA TRIAL SCHEDULED FOR COMPLETION IN TWO YEARS, the Menlo Park, Calif.- based company said following the Sept. 3 resumption of the 800-patient Phase III trial being conducted by marketing partner Warner-Lambert. The trial was suspended in July with very few patients enrolled after an analysis of Phase I/II studies found a "disparity" between the drug and placebo groups ("The Pink Sheet" Aug. 4, T&G-8).

"Detailed data analyses indicated that this [disparity] appeared to be due to small patient numbers and an unfortunate distribution of patients at randomization between the placebo and SNX-111 treatment groups," Neurex said. Phase II trials included 70 patients. Neurex pointed out that most head injury subjects have been in automobile accidents or similar events that cause substantial injuries to other parts of the body. Randomization occurred without taking other injuries into account and caused an artificial disparity between the groups, Neurex maintained. The company reviewed its conclusions with the Phase III data safety monitoring committee, the American Brain Injury Consortium and FDA before resuming the trial.

No changes have been made in the Phase III head trauma protocol. Neurex and Warner-Lambert expect that the higher number of patients in the trial will create a more equitable randomization.

The dose established in Phase II trials, 60 mg/day infused over three hours, will be used in the pivotal study. Safety data will also be retained from the earlier trials, although the ongoing study will be the only measure of efficacy.

The first indications for SNX-111 that could reach the NDA filing stage are malignant and chronic neuropathic pain syndromes. Neurex plans to complete enrollment in two 200-patient SNX-111 pain trials by year-end, followed by an NDA submission in three to six months. One trial involves patients with malignant AIDS- or cancer-related pain and the other examines non-malignant pain such as neuralgia or neuroma. The dose in the pain studies is 10,000 times lower than in the head trauma trial, Neurex pointed out, and the drug is given intrathecally rather than intravenously.

The NDA submission will include short-term efficacy data from the 200 patients with non-malignant pain and 100 of the malignant pain patients from an interim analysis. Long-term data from all patients will be included; the studies are of indefinite length. Neurex had a meeting with FDA and the Anesthetic & Life Support Drugs Advisory Committee in March to discuss the contents of the submission. The committee urged the company to obtain pediatric data and steady-state data from spinal fluid samples to look for gender-based dosing differences ("The Pink Sheet" April 7, T&G-9). The neuron-specific calcium channel blocker and non-opioid analgesic SNX-111 is also in Phase II trials to treat ischemia due to stroke or coronary graft bypass surgery.