On May 5, 2014 Novartis reported results from a pivotal Phase III trial of investigational therapy Signifor LAR (pasireotide LAR; SOM230) in patients with acromegaly for whom current standard of care provides inadequate disease control (Press release Novartis, MAY 5, 2014, View Source [SID:1234500489]). The study findings showed that patients taking pasireotide long-acting release (LAR) achieved greater disease control when compared to continued treatment with the standard somatostatin analogue therapies, octreotide LAR or lanreotide Autogel.
This study evaluated pasireotide LAR 40 mg and 60 mg against continued therapy with octreotide LAR or lanreotide Autogel in patients who did not achieve GH and IGF-1 biochemical control despite receiving the maximum approved doses of these currently available somatostatin analogues (SSAs). In the trial, significantly more patients achieved biochemical control with each dose of pasireotide LAR compared to the octreotide LAR and lanreotide Autogel control arm. Specifically, 15.4% and 20.0% of those with inadequately controlled acromegaly taking pasireotide LAR 40 mg and 60 mg, respectively (95% confidence interval [CI], 7.6-26.5; P=0.0006; 95% CI, 11.1-31.8; P<0.0001), achieved biochemical control versus 0% achieving biochemical control on continued treatment with octreotide LAR or lanreotide Autogel (95% CI, 0-5.3). The incidence and severity of adverse events (AEs) was similar across all treatment groups, except for a higher frequency and degree of hyperglycemia in the pasireotide LAR arm. Worldwide regulatory filings for pasireotide LAR in acromegaly are currently underway based on these results and separate previously published robust Phase III data.

On May 5, 2014 MEI Pharma reported that the first patient has been dosed in a Phase Ib clinical study (NCT02100007) of its investigational mitochondrial inhibitor drug candidate ME-344 in combination with Hycamtin (topotecan) in patients with solid tumors, including small cell lung and ovarian cancers. The open-label study is expected to enroll up to 64 patients with preliminary data anticipated by the first quarter of 2015 (Press release MEI Pharma, MAY 5, 2014, View Source [SID:1234500487]).
In October 2013, results from a Phase I clinical study of ME-344 were announced showing preliminary evidence of single-agent activity in patients with refractory solid tumors, including eight of 21 evaluable patients (38%) who achieved stable disease or better. Notably, one patient with small cell lung cancer achieved a confirmed partial response (PR) and still remains on study after more than 89 weeks. ME-344 was generally well tolerated in the study at doses equal to or less than 10 mg/kg delivered on a weekly schedule for extended durations. Dose limiting toxicities were observed at both the 15 and 20 mg/kg dose levels, consisting primarily of Grade 3 peripheral neuropathy.
The Phase Ib study now underway is evaluating the safety and tolerability of intravenous ME-344 in combination with Hycamtin, a chemotherapy approved by the U.S. Food & Drug Administration for the treatment of small cell lung, ovarian and cervical cancers. The initial stage of the study will establish the maximum tolerated dose (MTD) of ME-344 in combination with Hycamtin in up to 24 patients. Once the MTD has been determined, the study will enroll an additional 40 patients into two cohorts: relapsed/refractory small cell lung cancer and platinum-refractory ovarian cancer.
The open-label study is being conducted in collaboration with the Sarah Cannon Research Institute at the University of Oklahoma in Oklahoma City and Tennessee Oncology in Nashville.

On May 5, 2014 Cyclacel Pharmaceuticals reported that the Japanese Patent and Trademark Office issued two patents broadening the exclusivity of sapacitabine, the company’s lead clinical candidate (Press release Cyclacel, MAY 5, 2014, View Source [SID:1234500485]). Japanese Patent 5443763 claims novel pharmaceutical formulations of sapacitabine. Japanese Patent 5457196 claims methods of treating cancer comprising sapacitabine in combination with histone deacetylase (HDAC) inhibitors. Equivalent patents have been granted in the United States and other countries.

On May 5, 2014 Advaxis reported that it intends to initiate a clinical development program with its product candidate, ADXS-cHER2, for the treatment of pediatric osteosarcoma (Press release Advaxis, MAY 5, 2014, View Source [SID:1234500483]). ADXS-cHER2 is an immunotherapy that targets the HER2 oncogene, which is overexpressed in certain solid-tumor cancers, including pediatric bone cancer and breast cancer. In a veterinarian clinical study, pet dogs with naturally occurring osteosarcoma treated with ADXS-cHER2 after the standard of care showed a statistically significant prolonged overall survival benefit compared with dogs that received standard of care without ADXS-cHER2. Both veterinary and human osteosarcoma specialists consider canine osteosarcoma to be the best model for human osteosarcoma.