AB Science SA, of Paris, presented final results from its phase III study of masitinib in amyotrophic lateral sclerosis (ALS) at the European Network for the Cure of ALS meeting in Ljubljana, Slovenia, confirming findings from the interim analysis and showing that masitinib is effective in slowing down ALS disease progression. Masitinib was tested as an add-on to riluzole in ALS patients with a baseline ALSFRS-R progression rate of less than 1.1 points per month. Findings showed that masitinib administered at 4.5 mg/kg/day generated a therapeutic benefit when compared with placebo control, with significant slowing of disease evident in terms of ALSFRS-R (between-group difference of 3.4, p=0.0158) and ALSFRS-R slope (between-group difference of 27 percent), indicating a slowed loss of function; time elapsed between treatment initiation and disease progression measured by a decline in functional score (Var. ALSFRS-R) of nine points or death (p=0.0159), indicating delayed disease progression; and forced vital capacity (p=0.0332), which is considered a surrogate measure of overall survival.

Albireo Pharma Inc., of Boston, said the anticipated phase III program for A-4250, its candidate for patients with progressive familial intrahepatic cholestasis (PFIC), will includes a single randomized, double-blind, placebo-controlled, multicenter, six-month trial designed to enroll 60 patients and an open-label long-term extension study. The primary endpoint for FDA evaluation, and a key secondary endpoint for EMA evaluation, will be an assessment of change in pruritus, or itching. The primary endpoint for EMA evaluation, and a key secondary endpoint for FDA evaluation, will be serum bile acid (sBA) responder rate. Elevated sBA levels are associated with the pathogenesis of PFIC, and pruritus is a common and debilitating symptom of the disease. The trial, which Albireo first described in April, is expected to begin in the second half of 2017. (See BioWorld Today, April 25, 2017.)

Astellas Pharma Inc., of Tokyo, and partner Pfizer Inc., of New York, decided to discontinue the planned Endear trial, a phase III, randomized, international study comparing the efficacy and safety of Xtandi (enzalutamide) in combination with paclitaxel chemotherapy or as a monotherapy vs. placebo with paclitaxel in patients with advanced, diagnostic-positive, triple-negative breast cancer. No patients were ever enrolled in the trial. The companies have also decided that based on the Xtandi data from the phase II HER2-positive and ER/PR-positive breast cancer studies, there will not be follow-on phase III studies at this time.

Aurinia Pharmaceuticals Inc., of Victoria, British Columbia, reported that the first patient has been dosed in Aurora, the company's phase III confirmatory trial evaluating voclosporin for the treatment of lupus nephritis, an autoimmune disease caused by lupus that involves extreme inflammation and failure of the kidneys. The trial is a 52-week, global, double-blind, placebo-controlled study designed to demonstrate that voclosporin added to the current standard of care of mycophenolate mofetil can increase overall renal response rates in the presence of extremely low steroids. The primary endpoint is complete renal response at 52 weeks. About 320 patients will be recruited. The study is intended to support full marketing approval of voclosporin for patients with lupus nephritis by multiple regulatory authorities, the company said. In August, the company reported top-line data from AURA-LV showing that voclosporin, dosed at 23.7 mg twice daily, met the primary endpoint of complete remission at 24 weeks. (See BioWorld Today, Aug. 16, 2016, and Oct. 3, 2016.)

Autifony Therapeutics Ltd., of Stevenage, U.K., announced the start of a phase Ib biomarker study of the effect of AUT-00206, its Kv3 ion channel modulator, on patients with schizophrenia. Twenty-four patients, diagnosed with schizophrenia within the last five years, will receive AUT-00206 or placebo for 28 days. During that period, electrophysiological measures of central nervous function known to be impaired in schizophrenia will be investigated for signs of improvement, the company said. Participants will also undergo brain imaging, tests of cognition and tests of auditory function, in addition to routine safety monitoring. A key objective of the study is to characterize that range of biomarkers to inform the future development of the drug. The trial is being conducted in collaboration with King's College London.

Cellceutix Corp., of Beverly, Mass., said patient enrollment was completed in the third and final cohort of its phase II open-label, proof-of-concept trial evaluating defensin mimetic brilacidin as a noncorticosteroid, nonbiologic treatment for mild to moderate ulcerative proctitis/ulcerative proctosigmoiditis, two types of inflammatory bowel disease. Top-line results across all cohorts are expected in July.

Epizyme Inc., of Cambridge, Mass., reported interim data on its EZH2 inhibitor, tazemetostat, from the epithelioid sarcoma cohort of its ongoing phase II study in adult patients with molecularly defined solid tumors. Data from that cohort of patients (n=31), as of May 1, shows that treatment with tazemetostat resulted in a 32 percent disease control rate and a 13 percent overall response rate, with a median duration of response of seven months and ongoing. In addition, tazemetostat continues to demonstrate a favorable safety profile. The company also said it recently conducted a meeting with the FDA to discuss the registration strategy for tazemetostat for the treatment of epithelioid sarcoma and, based on those discussions, has identified a path to submission for accelerated approval of tazemetostat based on the 60-patient cohort from its phase II study. It will target an NDA submission in 2018.

Immune Design Corp., of Seattle, reported updated survival data from its clinical study testing CMB-305 as a monotherapy in soft tissue sarcoma, showing that, with a median follow-up exceeding 18 months and 11 months for LF-305 and CMB-305, respectively, median overall survival has not yet been reached in patients with recurrent disease. Durable disease control was observed in more than half of patients, including durable tumor growth arrest in patients who had evidence of disease progression prior to CMB-305 therapy. CMB-305 is a prime-boost vaccine approach against NY-ESO-1-expressing tumors.

Immunogen Inc., of Waltham, Mass., reported results from pooled analyses of three phase I expansion cohorts and from a phase Ib/II trial, FORWARD II, testing mirvetuximab soravtansine in combination with Avastin (bevacizumab, Roche Holding AG), carboplatin, Doxil (pegylated liposomal doxorubicin) or Keytruda (pembrolizumab, Merck & Co. Inc.). Data demonstrate the safety and efficacy profile of mirvetuximab soravtansine in the patient population eligible for the ongoing phase III registration trial, FORWARD I. Those data include 113 epithelial ovarian cancer patients treated with mirvetuximab soravtansine in three expansion cohorts in the phase I trial. In the subset of 36 patients meeting the key eligibility criteria for FORWARD I, which includes patients with platinum-resistant disease and medium or high levels of FRalpha and who have received up to three prior lines of therapy, the confirmed overall response rate was 47 percent and median progression-free survival was 6.7 months.

Merus NV, of Utrecht, the Netherlands, reported results from the phase I/II study of MCLA-128, a full-length IgG bispecific antibody with enhanced antibody-dependent cell-mediated cytotoxicity activity targeting the HER2 and HER3 receptors, in solid tumors. In the phase I portion, the recommended phase II dose was established as 750 mg every three weeks, based on safety and pharmacokinetic data. The phase II portion is ongoing, exploring selected metastatic indications, including breast, endometrial, ovarian, gastric and non-small-cell lung cancers. MCLA-128 was well-tolerated, with the ongoing phase II portion confirming the safety profile seen in the dose-escalation cohort.

MT Pharma America Inc., of Jersey City, N.J., presented open-label extension data at the European Network for the Cure of ALS meeting in Ljubljana, Slovenia, showing that patients with amyotrophic lateral sclerosis (ALS) treated with Radicava (edaravone) for 48 weeks (12 cycles) experienced significantly less decline in physical function, as measured by the ALS Functional Rating Scale-Revised, compared with patients given placebo for six months followed by six months of Radicava. Additionally, patients initially given Radicava had a roughly 58 percent relative risk reduction in death or certain disease progression events compared to those initially given placebo. There were no notable differences in the incidence of adverse events between groups other than contusion. Radicava, an intravenously administered antioxidant free radical scavenger, gained FDA approval earlier this month. (See BioWorld Today, May 9, 2017.)

Nanobiotix SA, of Paris, reported data showing the potential ability of NBTXR-3 to transform cold tumors into hot tumors. In the study, tumors from the ongoing two-arm phase II/III trial were examined both pre- and post-treatment in patients with locally advanced soft tissue sarcoma who had received either NBTXR-3 with radiotherapy (14 patients) or radiotherapy alone (12 patients). Results observed in the post-treatment examination of patients who received both showed a significant increase of immune cell infiltration (CD3+, CD8+). In contrast, there were no differences observed between pre- and post-treatment examination where patients received radiotherapy alone. Similarly, patients who received NBTXR-3 plus radiotherapy were found to have an increased immunoscore post-treatment, compared to those who received radiotherapy alone.

Neuralstem Inc., of Germantown, Md., said it completed dosing of the last subject in its phase II trial evaluating the efficacy of NSI-189 for the treatment of major depressive disorder. Top-line data are anticipated in the third quarter of this year. NSI-189 is an oral antidepressant believed to potentially promote remodeling of the hippocampus and reverse hippocampal atrophy.

Obseva SA, of Geneva, said it completed a phase I study testing potential drug-drug interactions of OBE-022 when given with magnesium sulfate, betamethasone, atosiban or nifedipine, medications typically used in women with preterm labor. All studied OBE-022 combination treatments were safe and well-tolerated. All but one treatment-emergent adverse events were mild, one was moderate; there were no serious adverse events and no clinically relevant changes in safety parameters. No clinically significant abnormalities were detected in clinical laboratory results and the ECG assessments, including QTcF evaluation, did not reveal any clinically significant abnormalities, the company said. OBE-022 is a once-daily, oral and selective prostaglandin F2alpha receptor antagonist, which is in development for the treatment of preterm labor in weeks 24 to 34 of pregnancy.

Recro Pharma Inc., of Malvern, Pa., presented data from its phase III study at the American Pain Society meeting in Pittsburgh, showing that intravenous meloxicam achieved the primary endpoint, a statistically significant difference in Summed Pain Intensity Difference over the first 48 hours compared to placebo (p=0.0034), along with detailed secondary endpoints and safety results in patients with acute postoperative pain following bunionectomy surgery. The study also achieved statistical significance for 15 secondary endpoints. Meloxicam is a long-acting, preferential COX-2 inhibitor.

Salix Pharmaceuticals Inc., of Bridgewater, N.J., said a study published in the Journal of Crohn's & Colitis showed that budesonide multimatrix 9 mg, administered once daily for eight weeks for the induction of remission of mild to moderate ulcerative colitis not adequately controlled by stable, oral mesalamine therapy, demonstrated efficacy and safety.

Shire plc, of Dublin, said The Lancet published results from a phase II study of SHP-647 (previously PF-00547659) to treat moderate to severe ulcerative colitis in adults. The 12-week, multicenter, double-blind, placebo-controlled, parallel-group study, dubbed TURANDOT, enrolled 357 patients with ulcerative colitis who failed at least one previous treatment. Participants were randomized to SHP-647 across dosing groups of 7.5 mg, 22.5 mg, 75 mg, and 225 mg or placebo. The study met the primary endpoint, which was the proportion of patients who achieved disease remission at week 12 compared to placebo. Remission rates at week 12 were highest in patients receiving 22.5 mg (12/72, 16.7 percent) and 75 mg (11/71, 15.5 percent) of the study drug and were significantly greater than placebo in three of the four treatment groups. The study also met its secondary endpoints at week 12, including the proportion of patients with a clinical response and the proportion of patients with mucosal healing in the treatment groups compared to placebo. SHP-647 appeared well-tolerated in the study. Shire expects to initiate a pivotal phase III trial of the anti-mucosal addressin cell adhesion molecule 1, or MAdCAM-1, antibody in the second half of the year. Last year, Shire licensed global rights to the candidate in all indications from Pfizer Inc., of New York.

Soligenix Inc., of Princeton, N.J., said long-term follow-up data from its phase II trial, in which SGX-942 (dusquetide), an innate defense regulator, demonstrated a significant reduction in the median duration of severe oral mucositis in patients with head and neck cancer, have been published in Biotechnology Reports. Those 12-month data further support the safety and tolerability of SGX-942, with the 1.5-mg/kg treatment group demonstrating accelerated tumor resolution and a decreased mortality rate relative to the placebo group. Results indicated that the tumor resolution was enduring and that the mortality rate in the SGX-942 1.5-mg/kg treatment group was lower (p=0.08) than the placebo group over the 12 months following completion of chemoradiation therapy. Soligenix recently was cleared to start a phase III trial testing SGX-942 in oral mucositis. (See BioWorld Today, May 4, 2017.)

Symic Bio Inc., of San Francisco, reported top-line results from the phase I/IIa MODIFY-OA trial, showing that SB-061, an intra-articular treatment for osteoarthritis of the knee, was found to be safe and well-tolerated with no drug-related serious adverse events and a very low rate of local adverse events (4.1 percent). Treatment with SB-061 resulted in a roughly 60 percent peak improvement in the Western Ontario and McMaster Universities Arthritis Index pain while walking score, the primary efficacy measure, although that measurement did not reach statistical significance relative to the saline control treatment group. In addition, positive trends in synovial fluid biomarker measures (e.g. reduction in inflammatory cytokine TNF-alpha) were observed in the SB-061 treatment group that reinforce the drug's intended mechanism of action in human studies for the first time. SB-061 is designed to be a functional mimic of aggrecan, a natural macromolecule of the extracellular matrix critical to the health of cartilage tissue.

Syndax Pharmaceuticals Inc., of Waltham, Mass., reported results from the melanoma cohort of the ongoing phase II ENCORE 601 trial of entinostat in combination with PD-1 inhibitor Keytruda (pembrolizumab, Merck & Co. Inc.), which met the pre-specified objective response criteria, with a minimum of two patients demonstrating a confirmed or unconfirmed objective response, to advance into the second stage of the trial. Data from the first cohort of patients indicate that four patients achieved an objective response by irRECIST criteria (three had a confirmed response; one had an unconfirmed response). ENCORE 601 is testing entinostat in patients whose disease has progressed despite prior treatment with anti-PD-1/PD-L1 therapies.