Addex Pharmaceuticals, of Geneva, said it started a Phase I trial evaluating the interaction of a new formulation of ADX10059 with proton-pump inhibitors and food. In 2007, ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, achieved clinical proof of concept demonstrating clinically and statistically significant effects in separate Phase IIa trials for gastroesophageal reflux disease and migraine. In preparation for Phase IIb testing, starting later this year, Addex developed a more commercial formulation of ADX10059.
Akesis Pharmaceuticals Inc., of San Diego, has completed recruitment and dosing phases in its placebo-controlled Phase IIa trial to test the safety and efficacy of AKP-020, a vanadium compound, in patients with Type II diabetes. Akesis dosed 10 patients with either 20 mg of AKP-020 or placebo. It originally planned to recruit and dose 21 patients but elected to discontinue the trial prior to the original endpoint in favor of advancing to a larger, multicenter, double-blind, dose-ranging study. The initial findings were encouraging, the company said, and results of the 10-patient trial and the plans for the larger study will be submitted to the FDA for review.
Callisto Pharmaceuticals Inc., of New York, said its wholly owned subsidiary Synergy Pharmaceuticals Inc. initiated oral dosing of healthy volunteers in a Phase I trial of SP-304 in gastrointestinal conditions. The primary objective is to assess safety and tolerability of an oral dose of SP-304 in healthy adult volunteers.
Celator Pharmaceuticals, of Princeton, N.J., reported positive results from its CPX-1 Phase II trial in patients with advanced colorectal cancer. The multicenter, open-label, Phase II study had two arms, irinotecan-naïve (IRI-naive) and irinotecan-refractory (IRI-refractory). Patients received 210 units/m2 of CPX-1 every two weeks. Twenty-six patients were treated in the IRI-naive arm. The overall response rate was 8 percent, and the disease control rate (patients who achieved a response or stable disease) was 65 percent. Median progression-free survival was 3.9 months. Six patients had a less than six-month PFS. Those data compared favorably to results published from other studies with irinotecan, which have shown a 4 percent response rate and median PFS of 2.5 months. Thirty-three patients were treated in the IRI-refractory arm. The disease control rate was 45 percent; no patient achieved an objective response. The median PFS was 2.3 months. Three patients had a less than six-month PFS. The disease control and median PFS are similar to results achieved in that patient population for approved agents (panitumumab or cetuximab monotherapy). Safety data were qualitatively similar to that of irinotecan and a fluoropyrimidine with neutropenia, diarrhea, nausea, vomiting and fluid loss events (dehydration and hypokalemia) being the most common. The 210 unit/m2 dose produced more toxicities than seen in the CPX-1 Phase 1 trial, resulting in only 40 percent of patients receiving less than 80 percent of the planned dose intensity. Treatment will be initiated at a lower dose in future studies.
Inovio BioMedical Corp., of San Diego, said partner Tripep AB, of Huddinge, Sweden, reported preliminary results indicating a dramatic reduction in hepatitis C viral load in its ongoing Phase I/II study of its ChronVac-C therapeutic DNA vaccine. That result is from the first patient in the middle dose group to complete treatment against hepatitis C virus infection. Samples taken before, during and after treatment showed that the viral levels in blood successively decreased by more than 95 percent during treatment.
Isotechnika Inc., of Edmonton, Alberta, reported successful results of a Phase IIb PROMISE trial. The primary endpoint (biopsy proven acute rejection, BPAR) was met in all three voclosporin dose groups. The results showed that voclosporin is as efficacious as tacrolimus, has the dose response expected in a Phase II trial and provides the rationale for dose selection for the Phase III program, the company said. Also, each dose was shown to be safe. Voclosporin demonstrated improvements over tacrolimus in several areas, specifically with respect to NODM, triglycerides, magnesium, insomnia and tremors. Data were presented at the 2008 American Transplant Congress in Toronto. Shares of Isotechnika (TSX:ISO) were down 28 cents, or 23 percent, to close at 93 cents.
Kosan Biosciences Inc., of Hayward, Calif., said that its lead Hsp90 inhibitor, tanespimycin, demonstrated a high level of antitumor activity in a Phase II trial when administered in combination with trastuzumab (Herceptin) to patients with HER2-positive metastatic breast cancer whose disease had either progressed after, or did not respond to, treatment with trastuzumab immediately prior to entering the trial. Of 27 evaluable patients, 17 patients showed clinical benefit including seven patients with partial response, five patients with tumor regression (minor response or MR) and five patients with extended stable disease (SD, greater than four cycles), yielding an overall clinical benefit incidence of 63 percent. Common toxicities were mainly mild to moderate and included fatigue and gastrointestinal symptoms.
Novacea Inc., of South San Francisco, said preliminary evaluation of its FDA-stopped ASCENT-2 data reflects median survival of 16.7 months in the treatment arm, which included Asentar in combination with once-weekly Taxotere, as compared to median survival of 18.5 months in the control arm of the study, in which Taxotere was administered every three weeks. In the treatment arm of ASCENT-2, 11.5 percent of androgen-independent prostate cancer patients completed their planned treatment, as compared to 21 percent of AIPC patients who completed their planned treatment in the control arm of the study. The overall incidence of grade 3 (severe) and grade 4 (life-threatening or disabling) adverse events was 51.4 percent in the treatment arm, as compared to 50 percent in the control arm. The FDA placed a clinical hold on the ASCENT-2 trial after a higher number of deaths occurred in the Asentar-treated group. The company said it is updating its data analyses and preparing a complete response to the FDA.
Nuvelo Inc., of San Carlos, Calif., has enrolled the first patient in a single-center, Phase Ib trial to determine the safety, tolerability and pharmacokinetics of bolus-plus-infusion dosing of NU172, a direct thrombin-inhibiting aptamer, in approximately 30 healthy male volunteers. The trial will study bolus dosing followed by escalating infusion doses of NU172 for up to four hours, mimicking the drug's potential administration in CABG surgery. The trial will be completed in the third quarter, and the company expects to begin a Phase II study late this year or early next year.
TorreyPines Therapeutics Inc., of La Jolla, Calif., has initiated a Phase I trial to evaluate the analgesic effect of NGX426, the oral prodrug of its lead product candidate, tezampanel. The trial will enroll 18 healthy volunteers and is designed to evaluate the compound's safety and tolerability and to assess the time of onset, magnitude and duration of its analgesic effect on hyperalgesia, an abnormally increased pain state, and allodynia, pain resulting from normally nonpainful stimuli to the skin, induced by intradermal injections of capsaicin. The primary endpoint is subject self-report of spontaneous pain following the injection of capsaicin.