Preclinical cancer drug data reveals MM efficacy
cancer cells from dying, has been shown to exhibit increased
anti-tumour activity when combined with an existing cancer
treatments. The data gives hope to those who have acquired drug
resistance from current therapies.
GlycoGenesys', GCS-100, targets Galectin-3 in multiple myeloma cells in vitro. Multiple myeloma is a bone marrow cancer in which white blood cells known as plasma cells, normally responsible for the production of infection-fighting antibodies, become abnormal and are overproduced.
The proliferation of these abnormal plasma cells, called myeloma cells, results in decreased production of normal blood cells and disease-fighting antibodies. In addition, this causes growth of tumours that spread to multiple sites - hence the term multiple myeloma (MM).
The decreased white blood cell production weakens the immune system and decreased red blood cell production leading to fatigue and weakness, while the myeloma tumours cause bone destruction, pain and fractures.
Preclinical data, generated at the Dana-Farber Cancer Institute has illustrated for the first time that GCS- 100 decreases Galectin-3 expression in MM cells when tested in combination with dexamethasone (a drug frequently used to treat MM).
Galectin-3 is over-expressed in a variety of cancers including MM, as well as solid tumours. It is a protein that protects cancer cells from dying. GCS-100 is currently in clinical testing for the treatment of MM and solid tumors.
The positive results arising for the pre-clinical trial has led to the commencement of Phase I/II dose escalation trials. The primary objective of the study is to evaluate the safety of GCS-100 when given to patients with relapsed or refractory multiple myeloma and to identify the recommended dose for future studies.
Secondary objectives are to evaluate the response to GCS-100 as a monotherapy and in combination with dexamethasone and determine the pharmacokinetics of GCS-100 alone and with dexamethasone.
"Our ongoing myeloma trial is designed to get two sets of results concerning GCS-100, both alone and in combination with dexamethasone," said Bradley Carver GlycoGenesys' CEO and an author of the paper.
This new preclinical data is quite relevant to our clinical trial strategy in multiple myeloma. Thus, our top priority is to continue generating human clinical data."
The preclinical data also revealed that GCS-100 had the potential to selectively kill and inhibit the growth of MM cells, including drug-resistant cells, as well as prevent metastasis in patients with MM.
GCS-100 was also found to overcome the protective effect of several proteins important for drug resistance and growth of multiple myeloma and other cancers, for example Bcl-2, Hsp-27, and NF-kB. GCS-100 also blocked the growth of multiple myeloma cells from patients resistant to Velcade, thalidomide, and dexamethasone.
"Collectively, these findings provide the frame work for clinical trials of GCS-100, either alone or in combination with dexamethasone, to enhance clinical efficacy, reduce toxicity, and overcome drug resistance to conventional and Velcade therapy in patients with relapsed/refractory MM," said the paper's authors.
Multiple Myeloma is the second most common heamatologic malignancy and although the disease is predominantly a cancer among older individuals (the average age of onset is 65 to 70 years of age), recent statistics indicate both increasing incidence and onset at a younger age.
In the United States, more than 50,000 individuals have MM and over 14,600 new cases of the disease are diagnosed each year. Worldwide, there are approximately 74,000 new cases and over 45,000 deaths due to multiple myeloma each year.
The study appears in the American Association of Cancer Researcher's publication Cancer Research, September 15, 2005; Vol. 65, No.18 edition.
