Abbott, of Abbott Park, Ill., said the first two-year data for Crohn's disease patients with fistulas showed that more than half of patients receiving Humira (adalimumab) had continued fistula healing. Those data, presented at the European Crohn's and Colitis Organization annual meeting in Lyon, France, were taken from two subanalyses of fistula patients from Abbott's 854-patient, one-year Phase III CHARM trial. Patients were followed through a second year of therapy into a nonplacebo controlled, ongoing open-label extension trial, with results showing that 60 percent experienced fistula healing at one year with Humira treatment and 76 percent had continued fistula healing over the next year. Seventy-one percent of the patients had at least a 50 percent reduction in the number of draining fistulas after treatment with Humira.
Amicus Therapeutics Inc., of Cranbury, N.J., is presenting positive results from a Phase II study of Plicera (isofagomine tartrate) in Gaucher's disease at the American College of Medical Genetics annual meeting in Phoenix, which support previously reported interim findings that Plicera was generally safe and well tolerated at all doses and increased target enzyme activity levels in a majority of patients. Thirty patients with Gaucher's disease (eight men and 22 women between the ages of 18 and 63) were enrolled, and there were 12 unique alleles represented, including the most common N370S and L444P mutations. In separate news, Amicus reported results from Phase I studies of AT2220 (1-deoxynojirimycin HCl) in Pompe disease, which showed no drug-related serious adverse events and no adverse events related to study treatment. Additional ex vivo response data with AT2220 showed that cells derived from 24 of 26 patients with evaluable data indicated dose responsive increases in acid alpha-glucosidase (GAA) levels, including 22 patients who had at least one copy of the common splice site mutation IVS1-13T>G. Amicus said those Phase I and ex vivo response results support advancing the product into Phase II trials in the first half of this year.
ArQule Inc., of Woburn, Mass., started patient dosing in a Phase I/II trial of ARQ 197 administered in combination with EGFR-inhibitor erlotinib (Tarceva) in patients with advanced non-small-cell lung cancer. ARQ 197 is an orally available, small-molecule inhibitor of the c-Met receptor tyrosine kinase. In addition to evaluating safety, tolerability and finding the recommended Phase II dose, the Phase I trial will evaluate the pharmacokinetic profile and assess the preliminary antitumor activity of the combination therapy. Pending the completion of that study, ArQule plans to initiate a Phase II trial, to compare ARQ 197 plus Tarceva against placebo plus Tarceva. ARQ 197 also is being evaluated in Phase II trials in microphthalmia transcription factor-driven tumors, which include clear-cell sarcoma, alveolar soft parts sarcoma and translocation-associated renal-cell carcinoma, and in pancreatic cancer.
Calando Pharmaceuticals Inc., of Pasadena, Calif., submitted an investigational new drug application to the FDA to initiate a Phase I trial of its lead cancer compound, CALAA-01. The drug candidate is a targeted nanoparticle, comprised of a proprietary, nonchemically modified siRNA against an M2 subunit of ribonucleotide reductase formulated with Calando's RONDEL (RNAi/Oligonucleotide Nanoparticle Delivery) polymer delivery system. The Phase I study is an open-label, dose-escalation trial in patients with nonresectable or metastatic solid tumors, and the primary objectives are to evaluate the safety and tolerability of CALAA-01 in humans. Additional objectives include characterization of pharmacokinetics, evaluation of tumor response and recommendation of a CALAA-01 dose for future clinical studies.
Clinical Data Inc., of Newton, Mass., initiated the second of its two pivotal trials of Vilazodone, the company's drug candidate for depression. The trial will enroll about 475 adult patients diagnosed with major depressive disorder and is designed to assess the mean change from baseline in the Montgomery-Asberg Depression Rating Scale total score compared to placebo as the primary endpoint. In addition, the trial will evaluate genetic biomarkers of response to Vilazodone, which may lead to the development of a pharmacogenetic test that would help determine the likelihood of a patient's positive response to the drug. Those biomarkers were identified during the first, successful pivotal trial of Vilazodone, which in September demonstrated both statistical and clinical significance on primary and secondary endpoints. Along with the long-term safety study of Vilazodone that began in December, the second pivotal trial is intended to support a new drug application for Vilazodone, expected in 2009. (See BioWorld Today, Sept. 5, 2007.)
Cytopia Ltd., of Melbourne, Australia, started dosing patients in the first of a suite of Phase II studies for its vascular disrupting agent, CYT997. Those studies will investigate the compound's activity in multiple myeloma and glioblastoma multiforme. Cytopia also intends to file an orphan drug designation application in the U.S. for CYT997 in multiple myeloma within three months. The company also is undertaking a feasibility analysis for a Phase II study in mesothelioma patients who have failed the currently approved drug, Alimta (pemetrexed).
Glycotex Inc., of Rockville, Md., said it completed patient enrollment in a Phase IIa study of GLYC-101 in wound closure in patients undergoing carbon dioxide skin resurfacing. The trial enrolled 12 patients undergoing laser skin ablation and is investigating the promotion of wound healing and cosmetic outcomes among efficacy endpoints. GLYC-101 is a topical gel designed to stimulate and modulate the natural cascade of wound healing activities of several cell populations.
Innocoll Inc., of Ashburn, Va., said the second of a series of planned Phase II trials sponsored by its wholly owned subsidiary, Innocoll Technologies Ltd., to investigate CollaRx Bupivacaine Surgical Implant for the management of postoperative pain, started dosing in the U.S. Innocoll previously completed a Phase II trial in patients undergoing hysterectomy surgery in the absence of gynecological cancers, and results of that trial showed evidence of sustained, postoperative analgesia for approximately 96 hours, as measured by VAS (visual analogue scale) scores, and reduced dependence on systemic morphine administered by patient-controlled analgesia. The U.S. trials will evaluate the implant in a variety of soft and hard tissue procedures - including hysterectomy, herniorrhaphy, open gastrointestinal surgery and orthopedic surgery.
MacroChem Corp., of Wellesley Hills, Mass., said results of two Phase III studies comparing the efficacy of an investigational topical antimicrobial peptide preparation, pexiganan acetate cream, against systemic therapy with an oral fluoroquinolone antibiotic, ofloxacin, in mildly infected diabetic foot ulcers showed that the rates of clinical cure or improvement for topical pexiganan and oral ofloxacin statistically were equivalent for the combined studies.
Millennium Pharmaceuticals Inc., of Cambridge, Mass., said updated results of the Phase I/II clinical trial of the combination therapy VELCADE, melphalan and prednisone (VcMP) in newly diagnosed multiple myeloma patients ineligible for stem cell transplantation showed an overall survival rate of 85 percent at 38 months with combination therapy compared to the 38 percent historical control with melphalan and prednisone. The median time to disease progression with Velcade combination treatment was 27.2 months vs. 20 months for historical control, and the median event-free survival was 25 months vs. 15 months for historical control. The study was pre-published online in Haematologica. The company submitted a supplemental new drug application in December to expand Velcade's use into newly diagnosed multiple myeloma patients. The PDUFA date is June 20.
Neoprobe Corp., of Dublin, Ohio, said final results from an 80-patient Phase II study designed to test the effectiveness of Lymphoseek in identifying lymphatic tissue determined that Lymphoseek accurately identified lymphatic tissue in 99 percent of the tissue identified by the drug. In addition, the pathology evaluation of the lymph nodes identified by Lymphoseek confirmed the presence of tumor in 22.4 percent of the melanoma patients and 22.6 percent of the breast cancer patients. No drug-related safety or adverse events were identified in the patients who participated in the study. Those data were presented at the 61st Annual Cancer Symposium of the Society of Surgical Oncology in Chicago.
Neurochem International Ltd., of Ecublens, Switzerland, said it will initiate a second Phase III trial with its investigational product candidate, eprodisate (KIACTA) in amyloid A amyloidosis in hopes of obtaining market approval from the FDA and the EMEA. The additional confirmatory efficacy Phase III trial will have a target significance level (p-value) of 0.05 rather than the p-value of 0.01. Data obtained from the first Phase II/III clinical trial yielded promising efficacy results on the study endpoints. Neurochem received its second approvable letter for Kiacta in July, with a request for additional data. (See BioWorld Today, July 19, 2007.)
Novelos Therapeutics Inc., of Newton, Mass., reached the target enrollment of 840 patients in the pivotal Phase III trial of NOV-002 in combination with first-line chemotherapy in advanced non-small-cell lung cancer. The randomized, open-label, international trial, being conducted under a special protocol assessment, is evaluating NOV-002 in combination with paclitaxel and carboplatin vs. paclitaxel and carboplatin alone, with a primary endpoint of median overall survival. The independent data monitoring committee has recommended continuation of the trial as planned at each of its quarterly data review meetings, and the trial will conclude upon reaching 725 events, expected in mid-2009.
Raven Biotechnologies Inc., of South San Francisco, said it initiated a Phase II study of RAV12, its lead clinical product, in combination with gemcitabine in metastatic pancreatic cancer. After an initial dose-escalation run-in segment of about 18 patients, the trial will enroll 63 patients in an efficacy segment. The target dose and schedule of RAV12, 0.75 mg/kg twice weekly, was chosen in a recently completed Phase I/IIa trial that involved 53 patients. Final analysis of the Phase I/II study will be available the third quarter of 2008.
Vertex Pharmaceuticals Inc., of Cambridge, Mass., and Tibotec Pharmaceuticals Ltd., of Cork, Ireland, said patient screening has begun in the ADVANCE study, a pivotal Phase III study of the hepatitis C virus (HCV) protease inhibitor telaprevir in combination therapy in treatment-naïve patients with chronic HCV infection. The ADVANCE trial will enroll 1,050 treatment-naïve genotype 1 HCV patients and will evaluate two 24-week telaprevir-based regimens in comparison to a 48-week control arm. The primary endpoint of the study is sustained viral response, defined as undetectable HCV RNA (<10 IU/mL) 24 weeks after the completion of treatment. In the study, rapid viral response criteria will be used to determine which telaprevir patients can stop all treatment at 24 weeks. (See BioWorld Today, Jan. 24, 2008.)