LA JOLLA, Calif., Oct. 22 TorreyPinesTherapeutics, Inc. (Nasdaq: TPTX) today announced that tezampanel met theprimary endpoint in a 306-patient, Phase IIb clinical trial for the treatmentof a single, acute migraine attack. In the study, which evaluated tezampaneladministered subcutaneously, the 40 mg dose demonstrated statisticallysignificant improvement on headache pain response at two hours post-dosecompared to placebo (78.2 percent versus 58.7 percent; p=0.033, corrected formultiplicity) and the response was sustained through 24 hours post-dose.Although not powered to demonstrate statistical significance, improvement inkey secondary measures at 40 mg, nevertheless, were either statisticallysignificant (p<0.050) or trending (p<0.100) when compared to placebo andcorroborated the results for the primary endpoint of the study. These keysecondary measures included nausea or vomiting, photophobia, a sum of painintensity scores at three and four hours post-dose, sustained headacheresponse at 24 hours, functional disability and a composite score of coremigraine symptoms at two and four hours post-dose that included measures ofheadache severity, nausea, vomiting, photophobia, phonophobia and functionaldisability. Two other doses of tezampanel, 70 mg and 100 mg, were evaluatedand also demonstrated effects across various pain measures although neitherdose reached statistical significance on the primary endpoint. The companyintends to submit the data from this trial to the U. S. Food and DrugAdministration (FDA) in order to initiate a Phase III program in acutemigraine in the second half of 2008.
In this trial, all three doses of tezampanel were well-tolerated. Therewere no serious or medically important adverse events reported. The mostcommon adverse events associated with all doses of tezampanel, as well asplacebo, were dry mouth, somnolence, dizziness, injection site burning andinjection site pain. Injection site burning and injection site pain were morefrequently reported in the placebo group. For tezampanel, the overallincidence of reported adverse events was dose related with the lowestincidence at the 40 mg dose.
"These data demonstrate that tezampanel unequivocally relieved migrainepain at a dose that is safe and well-tolerated," said Neil Kurtz, M.D.,President and Chief Executive Officer of TorreyPines. "I am proud thatTorreyPines is in a position to potentially offer migraine patients the firstnovel treatment option in more than a decade. We look forward to meeting withthe FDA to discuss advancing tezampanel into a Phase III trial in 2008."
"This is the second placebo-controlled trial to establish efficacy fortezampanel as a treatment for acute migraine," said Michael Murphy, M.D.,Ph.D., Chief Medical Officer of TorreyPines. "Previously, in a Phase IIa,double-blind, placebo and active-controlled trial, tezampanel, administeredintravenously, was more effective than placebo in relieving both migraine painand associated symptoms. The clinical trial data are encouraging and allow usto appropriately design a Phase III program in migraine."
Clinical Trial Design
This Phase IIb trial was an in-clinic evaluation of tezampanel in patientssuffering a single migraine attack, with or without aura. The clinical trialwas designed as a randomized, double-blind, placebo-controlled,parallel-group, multi-center trial. A total of 306 patients were enrolled at23 centers in the United States. Patients were equally randomized at eachcenter to one of four treatment arms and received 40 mg, 70 mg, or 100 mg oftezampanel or placebo as a single, subcutaneous dose.
The primary purpose of the trial was to identify a dose that could be usedin a Phase III development program for tezampanel in acute migraine. Theprimary efficacy endpoint was headache pain response at two hours post-dose.Secondary efficacy endpoints included the traditional endpoint