• Biomarin Pharmaceutical Inc., of San Rafael, Calif., dosed the first patient in its Phase III program to evaluate BMN 673, its poly ADP-ribose polymerase inhibitor, in the treatment of metastatic germline BRCA-mutated breast cancer. The open-label, randomized, parallel, two-arm, multicenter study will compare BMN 673 with physician’s choice in approximately 430 germline BRCA mutation patients with locally advanced and/or metastatic breast cancer who received no more than two prior chemotherapy regimens for metastatic disease. The primary endpoint is progression-free survival, with secondary endpoints of objective response rate and overall survival. Biomarin is using the BRACAnalysis test developed by Myriad Genetics Inc., of Salt Lake City, to stratify patients in the pivotal study. (See BioWorld Today, Oct. 3, 2013.)

• Clovis Oncology Inc., of Boulder, Colo., dosed the first patient in the global ARIEL2 (Assessment of Rucaparib in Ovarian Cancer Phase 2 Trial) study of rucaparib, its oral small-molecule poly ADP-ribose polymerase (PARP) inhibitor, to treat platinum-sensitive, relapsed ovarian cancer. The single-arm, open-label study is designed to identify tumor characteristics that predict sensitivity to rucaparib using DNA sequencing to evaluate each patient’s tumor. Tumor samples from study participants will be tested for BRCA1 and BRCA2 mutations and for other biomarkers that are expected to confer sensitivity to PARP inhibitor therapy. Patients in the study will receive both rucaparib and their molecular test results, including tumor BRCA status, and will be treated until their disease progresses or they withdraw from the study. By year-end, Clovis plans to initiate its pivotal study, ARIEL3. The randomized, double-blind, Phase III study will compare the effects of rucaparib against placebo to evaluate whether rucaparib in platinum-sensitive, ovarian, fallopian tube or primary peritoneal high-grade cancer patients can extend the period of time for which the disease is controlled. The study also will prospectively test whether a patient’s BRCA mutation status or other biomarkers predict their response to rucaparib. Provided the ARIEL studies succeed, the company plans to use data generated from the trials to submit a new drug application to the FDA for rucaparib as a maintenance drug in genetically appropriate patients with relapsed, platinum-sensitive ovarian, fallopian tube or primary peritoneal high-grade cancer.

• Cornerstone Pharmaceuticals Inc., of Cranbury, N.J., initiated a pilot Phase II trial of CPI-613 to treat patients with locally advanced or metastatic pancreatic cancer. The company’s lead altered energy metabolism directed, or AEMD, candidate is designed to disrupt the altered energy-production pathways in cancer cells. The interventional study, sponsored by the Comprehensive Cancer Center of Wake Forest Baptist Medical Center, will enroll patients with locally advanced or metastatic pancreatic cancer that cannot be surgically removed and is documented as having progressed after failing existing therapies. The primary endpoint of the study is overall survival, with secondary endpoints including overall response rate, progression-free survival and safety. The FDA granted orphan drug status to CPI-613 in pancreatic cancer in 2006. (See BioWorld Today, Oct. 19, 2009.)

• Cytodyn Inc., of Vancouver, Wash., said it submitted a revised protocol to the FDA relating to an upcoming Phase IIb trial of PRO 140, its lead product in development for HIV infection. Prior to Cytodyn’s acquisition of PRO 140 from Progenics Pharmaceuticals Inc., of Tarrytown, N.Y., in October 2012, initial screening had started, but Progenics halted the study for strategic business reasons. Current plans call for opening the study before the end of this year. PRO 140 is a humanized monoclonal antibody designed to block HIV co-receptor CCR5.

• Cytrx Corp., of Los Angeles, reported further data from a Phase IIb study comparing aldoxorubicin as a first-line treatment for advanced soft-tissue sarcomas vs. widely used doxorubicin. Results, presented at the Connective Tissue Oncology Society Meeting in New York, showed that aldoxorubicin can be administered at doses greater than 3.5 times the standard doxorubicin dose with similar or fewer systemic side effects. Patients treated with aldoxorubicin had a higher overall response rate (22 percent) vs. those treated with doxorubicin (p = 0.004), and a lower percentage of patients in the aldoxorubicin arm (32 percent) showed progressive disease vs. doxorubicin (50 percent) at the time of analysis. The study is still ongoing, and Cytrx expects to report top-line progression-free survival data in December.

• Edge Therapeutics Inc., of New Providence, N.J., enrolled the first patient in the Phase I/II NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) study of lead compound, EG-1962, a bioabsorbable nimodipine microparticle formulation to prevent delayed cerebral ischemia. The randomized, multicenter, open-label, controlled study will enroll up to 96 patients in approximately 20 centers to evaluate the safety, tolerability and pharmacokinetics of EG-1962 compared to the current standard of care, oral nimodipine, after subarachnoid hemorrhage (SAH). Exploratory endpoints will assess the ability of EG-1962 to reduce delayed cerebral ischemia (DCI) and improve clinical outcome compared to oral nimodipine, a calcium channel blocker. The first part of the study is a dose exploration phase of up to six dosing level cohorts with up to 12 patients per cohort, with a goal of establishing the dose of EG-1962 to take forward into a potential expansion phase. EG-1962 is being developed to prevent DCI, a life-threatening complication of SAH that typically results from a ruptured brain aneurysm or traumatic brain injury. The company plans to report data from the study in the first half of 2014.

• Entremed Inc., of Rockville, Md., said it started a Phase II study, titled “Phase II Study of Oral ENDM-2076 Administered to Patients with Ovarian Clear Cell Carcinomas.” The trial will examine the response and progression-free survival rates of ENMD-2076, an oral Aurora A/angiogenic kinase inhibitor.

• Esperion Therapeutics Inc., of Plymouth, Mich., said it dosed the first patient in a Phase IIb study of ETC-1002, an oral, once-daily small molecule, in patients with or without statin intolerance and hypercholesterolemia. The goals are to compare the LDL-C lowering efficacy of ETC-1002 with ezetimibe and to demonstrate comparable tolerability to ezetimibe in patients with elevated LDL-C levels. About 322 patients will be enrolled, and the primary objective is to assess the LDL-C lowering efficacy of ETC-1002 monotherapy vs. ezetimibe over 12 weeks. Secondary endpoints include assessing the drug’s effect on additional lipid and cardiometabolic biomarkers, characterizing the tolerability and safety and assessing the dose range of ETC-1002 to inform Phase III dosing.

• E-Therapeutics plc, of Oxford, UK, said it started a Phase IIb trial of ETS6103 in major depressive disorder. The study is evaluating the drug, a controlled-release version of tramadol, as a second-line treatment in patients who have not responded adequately to first-line therapy with a selective serotonin reuptake inhibitor. About 160 patients will be enrolled, and the primary objective is to test whether the two ETS6103 regimens have antidepressant activity that is noninferior to that of amitriptyline, as measured by the Montgomery-Asberg Depression Rating Scale, between randomization and end of treatment eight weeks later. Results are expected in the first half of 2015.

• Hospira Inc., of Lake Forest, Ill., presented results from two open-label extension studies of CT-P13 (infliximab) as a late breaker at the American College of Rheumatology/Association of Rheumatology Health Professionals meeting in San Diego. CT-P13, branded as Inflectra, was approved by the European Medicines Agency in September as the first biosimilar antibody to the reference product Remicade (infliximab, Johnson & Johnson). The open-label extension studies were designed to confirm the long-term efficacy and safety of Inflectra in patients who completed the original 54-week European Union clinical studies and to investigate switching from the reference Remicade product to Inflectra. In one study, 302 of 455 patients with rheumatoid arthritis who completed the Phase III PLANETRA study entered the open-label extension phase. Of those, 158 were treated continuously with Inflectra (maintenance group) and 144 were switched from Remicade to Inflectra (switch group) for one additional year. At weeks 78 and 102, the groups were similar as measured by ACR20/50/70, DAS28-CRP, DAS28-ESR, EULAR-CRP and EULAR-ESR response rates. Overall incidence of treatment-emergent adverse events (AE) was similar in both groups. In the other study, 174 of 210 patients with ankylosing spondylitis who completed the Phase I PLANETAS study entered the open-label extension phase. Of those, 88 were treated continuously with Inflectra and 86 were switched from Remicade to Inflectra for one additional year. Both groups were similar at weeks 78 and 102, as measured by ASAS20/ASAS40, ASAS partial remission and ASDAS-CRP rates. The AE profile for CT-P13 was generally consistent with the originator. The extension studies were conducted by Celltrion Inc., of Incheon, South Korea, which is developing eight monoclonal antibody biosimilars under a 2009 agreement with Hospira. (See BioWorld Today, Sept. 11, 2013.)

• Hyperion Therapeutics Inc., of South San Francisco, said it started enrolling patients in its THRIVE study, a long-term registry of patients with urea cycle disorders (UCD) designed to capture clinical outcomes and comparative effectiveness data. The prospective study aims to collect data in up to 500 UCD patients as part of their routine management and will track long-term outcomes, including hyperammonemic crisis, ammonia levels, growth and development and neurocognitive outcomes. Hyperion’s Ravicti (glycerol phenylbutyrate) was approved earlier this year for use in UCD patients. (See BioWorld Today, Feb. 4, 2013.)

• Kamada Ltd., of Ness Ziona, Israel, said preliminary data from its ongoing extension study of a Phase I/II trial of lead product Glassia in pediatric patients with recently diagnosed Type I diabetes (T1D) showed that at about 20 months from diagnosis and about 10 months following the last Glassia infusion, 60 percent of study subjects (12/20) who participated in the extension portion had peak C-peptide levels greater than 0.2 pmol/ml, which indicates a functioning beta cell capacity and is a higher percentage than expected without intervention. Kamada plans to initiate a Phase II/III trial testing Glassia, a ready-to-use liquid alpha 1-proteinase inhibitor, in newly diagnosed T1D pediatric and young adult patients.

• Protalex Inc., of Summit, N.J., said it initiated enrollment of its fifth and final cohort in a Phase IIb dose-escalation, multidose study of PRTX-100, a drug incorporating a highly purified form of staphylococcal protein A, in combination with methotrexate or leflunomide in adults with active rheumatoid arthritis. That cohort will enroll up to 16 patients and will include additional monthly maintenance doses of PRTX-100 in the 3 mcg/kg and 6 mcg/kg range. The primary objective of Cohort 5 is to assess safety and tolerability of one of those doses administered on a modified schedule, while secondary objectives include determining the effects of PRTX-100 on measures of disease activity, assessing the immunogenicity and evaluating pharmacokinetic parameters after repeated doses.

• Synergy Pharmaceuticals Inc., of New York, said it started a Phase II trial to test the safety and efficacy of SP-333, a second-generation GC-C agonist and once-daily oral treatment, in patients with opioid-induced constipation. The study will compare a four-week, dose-ranging regimen of SP-333 against placebo in patients taking analgesics for chronic, noncancer pain for at least three months. The trial will enroll about 260 patients who have fewer than three spontaneous bowel movements (SBMs) per week and who experience constipation-related symptoms. The primary endpoint is mean change from baseline in the number of SBMs during week four of the treatment period.

• Xoma Corp., of Berkeley, Calif., reported results from two Phase II studies testing gevokizumab, its monoclonal antibody designed to bind to interleukin-1 beta, Results from the study in erosive osteoarthritis of the hand patients with elevated C-reactive protein levels greater than or equal to 2.5 mg/L showed that patients treated with gevokizumab experienced a greater lowering in their mean Austrialian/Canadian Osteoarthritis Hand Index (AUSCAN) scores at day 84 compared to patients in the placebo-treated group. After three months of treatment, those receiving gevokizumab demonstrated a 23 percent reduction from baseline in the composite AUSCAN score compared to a 14 percent reduction in the placebo arm. The trial enrolled a total of 85 patients. Results from a pilot study testing in pyoderma gangrenosum (PG), a rare ulcerative skin disease, showed that three of the first four patients treated with gevokizumab showed improvement in ulcer size by day 28, and one patient had total resolution of the ulcer by day 84. Based on data from that cohort, which tested 60-mg doses delivered monthly for three months, Xoma opted not to enroll patients in the higher-dose cohort. The company said it will request a meeting with the FDA to discuss the data and requirements for moving gevokizumab into a pivotal Phase III program in PG.