Acadia Pharmaceuticals Inc., of San Francisco, initiated the phase II CLARITY trial to evaluate pimavanserin for adjunctive treatment in patients with major depressive disorder following an inadequate response to first-line therapies for clinical depression. The 10-week randomized, double-blind, placebo-controlled, multicenter study is expected to enroll approximately 188 patients, randomized to 34 mg of pimavanserin or placebo, orally, once daily, in addition to their ongoing antidepressant. The primary endpoint is change from baseline on the Hamilton Depression Rating Scale, or HAM-D, total score. The selective serotonin inverse agonist, which preferentially targets 5-HT2A receptors, was approved earlier this year as Nuplazid to treat hallucinations and delusions associated with Parkinson's disease psychosis. (See BioWorld Today, May 3, 2016.)
Aicuris Anti-infective Cures GmbH, of Wuppertal, Germany, enrolled the first subject in a phase II study evaluating topical pritelivir, a small-molecule helicase-primase inhibitor, for the treatment of recurrent labial herpes (cold sores), the most evident sign of herpes simplex virus (HSV) type 1. Topical pritelivir recently achieved the primary endpoint in a phase I trial with healthy volunteers and did not show any cumulative irritation potential. Pritelivir (oral) has already shown superiority against the standard of care, valaciclovir, in a phase II trial in patients with genital HSV-2 infections, the company said.
Aradigm Corp., of Hayward, Calif., disclosed top-line results from two phase III trials, ORBIT-3 and ORBIT-4, evaluating the safety and efficacy of Pulmaquin, the company's formulation of once-daily ciprofloxacin for inhalation, in patients with non-cystic fibrosis bronchiectasis (non-CF BE) with chronic lung infections with Pseudomonas aeruginosa. The ORBIT-3 and ORBIT-4 pivotal experiments were identical in design except for a pharmacokinetics substudy that was conducted in one of the trials. The primary endpoint in both ORBIT-3 and ORBIT-4 was an increase in the median time to first mild, moderate or severe pulmonary exacerbation (PE). The key secondary efficacy endpoint in both trials was the frequency of PEs over the 48-week double-blind treatment period. In ORBIT-4, the median time to first mild, moderate or severe PE was 230 days in the Pulmaquin treatment group as compared to 163 days in the placebo group. That increase in the median time to first PE was statistically significant (p=0.0462) using non-stratified log-rank analysis. In the key secondary efficacy endpoint, there was a 37 percent reduction in the frequency of PEs over the 48-week treatment period in the Pulmaquin treatment group as compared to the placebo group. That result was statistically significant (p=0.0007) with a hazard ratio (HR) of Pulmaquin/placebo of 0.63 using non-stratified binomial regression. In ORBIT-3, the median time to first mild, moderate or severe PE was 221 days in the Pulmaquin treatment group as compared to 136 days in the placebo group. That increase in the median time to first PE was similar to ORBIT-4 but was not statistically significant (p=0.8488) using non-stratified log-rank analysis. In the secondary endpoint, there was a 13 percent reduction in the frequency of PEs over the 48-week treatment period in the Pulmaquin treatment group as compared to the placebo group. That result was not statistically significant (p=0.3125) with an HR of Pulmaquin/placebo of 0.87 using non-stratified binomial regression. The analyses of combined data from both studies resulted in a statistically significant reduction in the number of PEs over the 48-week double-blind period (HR Pulmaquin/placebo: 0.73; p=0.0015), representing a 27 percent reduction in PEs over the period. Shares of Aradigm (NASDAQ:ARDM) closed Thursday at $2.29, down $2.95, or 56.3 percent.
Cellectar Biosciences Inc., of Madison, Wis., updated results from the first two cohorts of its phase I study testing CLR 131, which delivers cytotoxic radioisotope iodine-131 to tumor cells via the PDC delivery platform, in patients with relapsed or refractory multiple myeloma. The clinical benefit rate for the study is 80 percent, despite patients receiving an average of four prior treatments, including stem cell transplant and triple-drug combinations. At this time, cohort 1 (12.5 mCi/m2 dose) and cohort 2 (18.75 mCi/m2 dose) patients have demonstrated post-treatment median survival of 11.9 months and 4.9 months, respectively. The median overall survival is not yet evaluable. All evaluable patients in the study experienced progression-free survival (PFS), with cohort 1 patients averaging 88.5 days of PFS, and patients in cohort 2 achieved an average PFS of 127 days, with that figure increasing as one of the four patients is still experiencing PFS.
Celsion Corp., of Lawrenceville, N.J., said the independent data safety monitoring board completed its safety review of the first four patient cohorts in the ongoing phase Ib OVATION study and recommended the trial continue as planned. Celsion will proceed with completing dosing in the fourth and final cohort. OVATION is a dose-escalating trial combining GEN-1, the company's DNA-based immunotherapy, with the standard of care for the treatment of newly diagnosed patients with advanced ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery.
CSL Ltd., of Melbourne, Australia, said it advanced three therapies based on targeted monoclonal antibody (MAb) technologies into phase I studies in Australia. CSL324 is an anti-GCSFR MAb that could be used to treat rare inflammatory diseases caused by overactive neutrophil activity. CSL324 works by regulating white blood cell activity in autoimmune disease to prevent overactive neutrophils from destroying healthy tissue. The phase I trial will explore proof of biological concept, with particular focus on identifying effective therapeutic dosing. CSL312 is an anti-factor XIIa MAb in development to treat multiple indications, including hereditary angioedema, and to prevent thrombosis. CSL346 is an anti-VEGF-B MAb that could be used to control glucose absorption in insulin-resistant patients with type 2 diabetes by targeting fatty acid metabolism.
Cytokinetics Inc., of South San Francisco, activated the first clinical site and started the GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) phase III cardiovascular outcomes trial of omecamtiv mecarbil, being conducted by partner Thousand Oaks, Calif.-based Amgen Inc. The news triggered a $26.7 million milestone payment to Cytokinetics. In clinical studies, omecamtiv mecarbil, a cardiac myosin activator, has been shown to enhance cardiac function by increasing cardiac contractility and is being developed for the potential treatment of patients with chronic heart failure. GALACTIC-HF will enroll about 8,000 symptomatic chronic heart failure patients who are either currently hospitalized for a primary reason of heart failure or have had a hospitalization or admission to an emergency room for heart failure within one year prior to screening. The primary endpoint is a composite of time to cardiovascular death or first heart failure event, which is defined as either a hospitalization for heart failure or other urgent treatment for worsening heart failure. Secondary endpoints include time to cardiovascular death; patient-reported outcomes as measured by the Kansas City Cardiomyopathy Questionnaire Total Symptom Score; time to first heart failure hospitalization; and all-cause death.
Deciphera Pharmaceuticals Inc., of Waltham, Mass., presented top-line data from an ongoing phase I dose-escalation study of oral DCC-2618, a pan-KIT and PDGFR-alpha-targeted tyrosine kinase inhibitor in development to treat genetically defined cancers, including gastrointestinal stromal tumors (GIST) and other KIT-driven diseases, such as systemic mastocytosis, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich. Findings on the first 24 patients showed that partial metabolic responses, using EORTC criteria, were observed in 14 of 15 patients with KIT-mutant GIST, along with initial signs of decreases in circulating tumor DNA that codes for KIT, suggesting broad-spectrum inhibition of KIT mutants in heavily pretreated GIST patients harboring multiple resistance mutations. Two patients achieved partial response, measured by RECIST criteria. DCC-2618 was well-tolerated with an encouraging safety profile. The most common treatment emergent adverse events (>25 percent) included fatigue, dyspnea, anemia and decreased appetite. One dose limiting toxicity, a grade 3, asymptomatic lipase elevation in the 100 mg cohort, was reported. The company said the maximum tolerated dose for DCC-2618 was not yet reached in the study. (See BioWorld Today, Sept. 22, 2015.)
Ensysce Biosciences Inc., of San Diego, said it treated the first two patients in a phase I trial of PF614, its two-step extended-release oxycodone prodrug designed with abuse-deterrent properties. The single-center, dose-escalation study is expected to treat up to six cohorts of eight healthy individuals randomized to PF614 or Oxycontin (oxycodone) to evaluate safety and pharmacokinetics.
Fennec Pharmaceuticals Inc., of Research Triangle Park, N.C., said The Lancet Oncology published results from the Children's Oncology Group, titled "Effects of Sodium Thiosulfate versus Observation on Development of Cisplatin-Induced Hearing Loss and Survival in Children with Cancer: Results from the Children's Oncology Group ACCL0431 Randomised Cohort Trial." Sodium thiosulfate was identified as an effective otoprotectant, and Fennec is developing the compound for use in supportive care for patients undergoing cancer treatment.
Ignyta Inc., of San Diego, reported data from an ongoing phase I/Ib trial at the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Munich, showing that RXDX-105, its VEGFR-sparing RET inhibitor, demonstrated clinical activity in patients harboring RET molecular alterations, with five out of nine patients with RET fusion-positive cancers who were RET inhibitor-naïve achieving a RECIST response (one complete response, three partial responses and one unconfirmed partial response), for a preliminary objective response rate of 56 percent. The trial has enrolled a total of 91 patients with a range of solid tumors.
Pfizer Inc., of New York, reported top-line results of a study testing Lyrica (pregabalin) Capsules CV and Oral Solution CV as adjunctive therapy in pediatric epilepsy patients, ages 4 to 16, with partial onset seizures. Results showed that adjunctive treatment with Lyrica 10 mg/kg/day resulted in a statistically significant reduction in seizure frequency vs. placebo, the primary efficacy endpoint. Treatment with Lyrica 2.5 mg/kg/day resulted in a numerical reduction in seizure frequency, which was not statistically significant. The Lyrica Pediatric Epilepsy Program is composed of a total of six studies in patients with epilepsy and is evaluating the drug as adjunctive therapy. Three trials have been completed and three are actively enrolling.
Pharmacyte Biotech Inc., of New York, said the FDA granted a request for a pre-IND meeting. The firm is developing a pancreatic cancer therapy using its live-cell encapsulation Cell-in-a-Box technology plus low doses of chemotherapy drug ifosfamide.
Shionogi & Co. Ltd., of Osaka, Japan, presented data at the Asia-Pacific Congress of Clinical Microbiology and Infection in Melbourne, Australia, from a phase II study of S-033188, a cap-dependent endonuclease inhibitor targeting influenza. Data from the 400-patient, randomized trial showed that 40-mg S-011388 was associated with a shorter time to alleviation of systemic symptoms compared with placebo, such as feverishness/chills (median 23 hours vs. 28.8 hours, p=0.0216), headache (37.9 hours vs. 43.7 hours, p=0.0304), fatigue (31.1 hours vs. 42.7 hours, p=0.0463) and aches and pains (25.4 hours vs. 41.9 hours, p=0.0145) and provided more rapid resolution of fever (28.9 hours vs. 45.3 hours, p<0.0001). With regard to respiratory symptoms, nasal congestion was more rapidly resolved with 40-mg S-033188 vs. placebo (21.9 hours vs. 42.8 hours, p=0.0081); however, sore throat and cough tended to persist despite rapid viral clearance in patients treated with S-033188. Shionogi has initiated a phase III program targeting otherwise healthy individuals and those at high risk of influenza-associated complications.
TNK Therapeutics Inc., of San Diego, a subsidiary of Sorrento Therapeutics Inc., said it plans to submit an IND in the first half of 2017 for its chimeric antigen receptor expressing T-cell (CAR T) programs for the treatment of hematological malignancies. To date, the anti-CD38 CAR T cells have demonstrated specific activation through the CAR resulting in the production of cytokines and CAR T proliferation. CD38-expressing multiple myeloma tumor cells were killed efficiently in vitro, and the CD38 CAR T cells completely eradicated tumors in a xenograft mouse model of human multiple myeloma.