A trio of Phase IIa studies is pointing to the promise of Tocosol Paclitaxel, a cancer product being developed by Sonus Pharmaceuticals Inc.
The Bothell, Wash.-based business reported data on its lead drug at the International Conference on Molecular Targets and Cancer Therapeutics in Boston, jointly sponsored by the American Association for Cancer Research, the National Cancer Institute and the European Organization for Research and Treatment of Cancer. The company also reported data at the Chemotherapy Foundation Symposium in New York.
Treatment with Sonus' reformulated paclitaxel product has shown it to be safe and well tolerated, as well as having antitumor effects.
Findings from the most recent studies, which are fully enrolled and are evaluating the drug's use in 122 patients with ovarian, bladder and non-small-cell lung cancers, showed no neuropathy in 70 percent of patients. Grade 3 neuropathy was reported in 9 percent, while there was no Grade 4 neuropathy. Also, Grade 3-4 neutropenia was observed in one-third of patients, while febrile neutropenia was reported in 2 percent.
Objective antitumor responses were observed in 31 percent of ovarian cancer patients. Thirty-three percent of those with bladder cancer had antitumor responses, and 21 percent of lung cancer patients had responses.
The company said it is beginning additional studies to provide data that would form the basis for potential FDA approval.
In other news from the conference:
• Ariad Pharmaceuticals Inc., of Cambridge, Mass., said preclinical results showed that AP23573, its lead oncology candidate, promotes anti-angiogenesis by blocking growth factor pathways activated by vascular endothelial growth factor (VEGF) in tumors and surrounding tissues. Previously, AP23573 had been shown to starve cancer cells and shrink tumors by inhibiting the cell-signaling protein mTOR, which regulates nutrient use and growth factor stimulation. Separately, Ariad reported the high-resolution structure of another small-molecule drug, AP23464, bound to a cancer-associated kinase target known as Src, which plays a role in the growth, proliferation and spread of many tumor, it said.
• Baylor College of Medicine in Houston said its researchers discovered the neuroblastoma-derived secreted protein, which is found only in the cells of the childhood cancer neuroblastoma. They said the finding could provide a new target for treatments and a new marker for the disease.
• Genta Inc., of Berkeley Heights, N.J., said preclinical results showed that Genasense (oblimersen sodium), its lead oncology candidate, caused an increase in apoptosis and a reduction in clonogenic survival among treated prostate cancer cells, compared with cells treated with control oligonucleotides. Separately, investigators from the University of Texas M.D. Anderson Cancer Center in Houston showed that when compared with controls, cells treated with Genasense plus radiation showed downregulation of Bcl-2 and increased cell death.
• GenVec Inc., of Gaithersburg, Md., said Phase II dose-escalating data showed that its lead oncology product, TNFerade, increased the percentage of patients who were progression free at three months post-treatment from 25 percent at a lower dose to 50 percent treated at a higher dose. Phase I findings revealed no dose-limiting toxicities, and the maximum tolerated dose was not reached.
• The Gray Cancer Institute in London said its researchers showed that molecular markers allowed them to identify eight distinct groups of tumors, each with similar biological profiles, within a patient group. One group of tumors had a better-than-average response to radiotherapy, with a success rate of 67 percent at five years compared to a 52 percent overall success rate. A second group showed a poor response to radiotherapy, with a success rate of 37 percent at five years.
• NaPro BioTherapeutics Inc., of Boulder, Colo., and the University of Alabama said linking a tumor-specific peptide called NBT-300 with paclitaxel might be the basis for a targeted antitumor therapy. The selective tumor-specific conjugate appears to target a variety of cancers expressing the specific peptide receptor. NaPro is targeting the bombesin receptor, which it called common to a variety of tumor types.
• Nereus Pharmaceuticals Inc., of San Diego, said preclinical results showed that NPI-2358 induces rapid vascular collapse and tumor growth inhibition in solid tumor models. The effects are seen upon monotherapy and as a marked potentiation of standard chemotherapeutic treatment. NPI-2358 is an analogue of a new class of small-molecule agents that was identified originally in an extract of a marine fungus, Aspergillus sp.
• Novuspharma SpA, of Milan, Italy, said preclinical results showed that Pixantrone does not significantly increase existing anthracycline-induced heart damage, while repeat treatment with traditional anthracyclines leads to significant deterioration in heart tissue. The findings suggest Pixantrone is safe to use in patients heavily pre-treated with existing anthracyclines, the company said, adding that the same conclusion has been reached in clinical trials of Pixantrone for relapsed aggressive non-Hodgkin's lymphoma.
• Praecis Pharmaceuticals Inc., of Waltham, Mass., said preclinical results showed that PPI-2458 inhibited tumor growth and that the degree of growth inhibition was linked to the level of MetAP2 inhibition by the compound. Separately, the NCI reported data showing that PPI-2458's anti-angiogenic activity and in vivo efficacy compare favorably to that of another compound of the class called TNP-470. Praecis said PPI-2458 recently entered a Phase I study for non-Hodgkin's lymphoma.
• The University of Washington School of Medicine in Seattle said its researchers showed that imaging of estrogen receptors using F-18-fluoroestradiol positron emission tomography might predict the response of advanced breast cancer to endocrine therapy by measuring regional target expression.
• Xenova Group plc, of Slough, UK, said four abstracts pointing to the mechanism of action of XR5944 (MLN944) show that the new DNA/RNA targeting agent is distinct from current cytotoxic agents. The compound maintains its cytotoxicity in yeast cells deficient in topoisomerases, though it was previously thought to exert its cytotoxic action by dual inhibition of topoisomerases-I and -II. Also, XR5944 arrests human tumor cell lines in both the G1 and G2 phases of the cell cycle, in contrast to topoisomerase inhibitors that arrest at the S/G2 phase. XR5944 is in Phase I development in patients with advanced solid tumors.