Here is the daily “fix” for you myeloma techno junkies out there who have requested more study results for ASH:
REDWOOD CITY, Calif., Dec. 7, 2009 (GLOBE NEWSWIRE) — Threshold Pharmaceuticals, Inc. (Nasdaq:THLD) today announced preclinical results related to Threshold’s clinical stage hypoxia-activated prodrug, TH-302. The results were presented today at the American Society of Hematology (ASH) Meeting being held December 5 to 8, 2009, in New Orleans, LA.
“Hypoxia is known to be linked to increased metastatic potential and poorer disease outcomes,” said Karin Vanderkerken, Ph.D., Department of Hematology and Immunology-Myeloma Center Brussels, Belgium. “This study has demonstrated that hypoxia exists in the bone marrow in an established model of myeloma and, importantly, TH-302 has had an impressive treatment effect in this preclinical model.”
Hypoxia is known to be associated with poor prognosis and tumor progression in solid tumors. Scientists have also been studying the effects of hypoxia on hematopoetic stem cells in the bone marrow. Thus, a preclinical study was undertaken to evaluate the hypoxic condition in the bone marrow in a murine model of multiple myeloma (MM), the 5T33MM syngeneic model, using the hypoxia-activated prodrug, TH-302.
The study found that almost all of the MM cells in the model reside in a hypoxic environment in the bone marrow and that these tumor cells may be a target for tumor-specific treatment with TH-302. In vivo, animals treated prophylactically with TH-302 showed decreased serum paraprotein compared to those not treated with TH-302. The frequency of apoptotic MM cells in bone marrow sections was also significantly increased in animals treated with TH-302. In vitro, 5T33 cell-based assays demonstrated TH-302 induces cell cycle arrest and triggers apoptosis in an oxygen concentration-dependent manner. Taken together, these results support continued investigation with TH-302 as a potential treatment for multiple myeloma.
Facet Biotech Corporation (NASDAQ:FACT) along with Bristol-Myers Squibb Company have announced that the interim data from the study of elotuzumab is promising. CEO and President of Facet Biotech, Faheem Hasnain mentioned that the preliminary data showed that elotuzumab in combination with lenalidomide and dexamethasone may have potential as a treatment option for patients with multiple myeloma and also that they are working closely with their partners at Bristol-Myers Squibb to finalize next steps for the elotuzumab development program, and anticipate initiating a global Phase II study in the first half of 2010.
Facet Biotech is a biotechnology company which is dedicated to advancing its pipeline of five clinical-stage products, leveraging its research and development capabilities to identify and develop new oncology drugs and applying its proprietary next-generation protein engineering technologies to potentially improve the clinical performance of protein therapeutics. Elotuzumab is a humanized monoclonal antibody directed against CS1, a cell-surface glycoprotein that is highly and uniformly expressed on multiple myeloma cells but is minimally expressed on normal cells.
The ongoing Phase I/II study of elotuzumab plus lenalidomide and low-dose dexamethasone evaluated multiple doses of elotuzumab in patients with multiple myeloma. The interim results given as an oral presentation today showed that of the 28 treated patients in the trial, 23 (82 percent) had an objective response by International Myeloma Working Group (IMWG) criteria. Another subset analysis showed that of 22 patients who had not previously received lenalidomide treatment, 21 patients (95 percent) achieved an objective response. The study is also evaluating safety, pharmacokinetics (PK) and clinical response.
CAMBRIDGE, Mass., Dec 08, 2009 (BUSINESS WIRE) — CombinatoRx, Incorporated today announced that preclinical data from its Adenosine A2A receptor (A2A) and Beta-2 Adrenergic Receptor (b2AR) Agonist oncology programs demonstrated synergistic anti-cancer activity when combined with standard-of-care therapies in multiple myeloma and other B-cell malignancies. These data, which demonstrate the benefit of the CombinatoRx combination high-throughput screening technology, were presented at the American Society for Hematology (ASH) 2009 Annual Meeting in New Orleans on December 7, 2009.
Key findings of the preclinical data include:
— A2A or b2AR agonists, exhibit highly synergistic anti-proliferative activity when combined with standard-of-care multiple myeloma therapies, such as dexamethasone, lenalidomide, bortezomib, melphalan and doxorubicin at clinically relevant concentrations.
— Synergy of the combinations was maintained in cells after chronic exposure with either single agent potentially reducing emergence of drug resistance.
— Synergistic combinations of A2A and b2AR agonists are highly selective for B-cell malignancies and in particular, diffuse large B-cell lymphoma and multiple myeloma. Substantial combination activity is observed in several cell lines resistant to standard-of-care agents.
— Synergistic drug combinations improve therapeutically relevant selectivity and can circumvent drug resistance.
— New insights into the potential molecular mechanism of action of these novel combinations have been identified using gene expression profiling.
“This data on the CombinatoRx A2A and b2AR agonist programs for the treatment of B-cell malignancies including drug resistant multiple myeloma is very encouraging,” said Robert Forrester, Interim President and CEO of CombinatoRx. “More broadly, the data presented at ASH underscores the utility of the CombinatoRx systematic combination screening technology in the identification and evaluation of pathway and chemical interactions relevant to disease.”
These are three of dozens of on-going pre-clinical and clinical trails which are progressing “under the radar” or shadow of larger, big splash drug trials like Onyx’s Carfilzomib. I’ll throw some of these in now and then for perspective. Maybe it will be one of these less publicised studies, and not Carfilzomib or a four or five drug cocktail of existing drugs, which will be the real difference maker for myeloma patients down the road. Feel good and keep smiling! Pat