Oct 31, 2019
DEP® gemcitabine outperforms Gemzar® in human pancreatic cancer model
- Starpharma advances a new internal DEP® candidate, DEP® gemcitabine, into development
- DEP® gemcitabine demonstrated significantly enhanced anti-tumour activity compared with Gemzar® (gemcitabine), both alone and in combination with Nab‑paclitaxel (Abraxane®), in a human pancreatic cancer model
- Gemzar® (gemcitabine), used alone or in combination with Abraxane®, is the current standard of care therapy for pancreatic cancer
- A patent has been filed for Starpharma’s proprietary DEP® gemcitabine, providing coverage to 2040
Melbourne, Australia: Starpharma (ASX: SPL, OTCQX: SPHRY) today announced results for its next internal development candidate, DEP® gemcitabine.
Starpharma’s proprietary DEP® gemcitabine demonstrated significantly enhanced anti‑tumour activity compared with Gemzar® (gemcitabine), both alone and in combination with Nab-paclitaxel (Abraxane®) in a preclinical human pancreatic cancer model. This data has formed the basis of a new patent application, which will provide coverage over DEP® gemcitabine to 2040. DEP® gemcitabine is one of several internal DEP® candidates under preclinical development by Starpharma.
DEP® gemcitabine is a DEP® version of Lilly’s Gemzar® (gemcitabine) - a well-established anti-cancer drug, which had peak sales of US$1.7 billion. Gemzar® (gemcitabine) is one of the leading chemotherapeutic drugs used to treat pancreatic cancer. It can be administered as a monotherapy or in combination with other therapies such as Abraxane®.
DEP® gemcitabine demonstrated significantly improved anti-tumour activity, compared to Gemzar®, the standard form of gemcitabine, in the human pancreatic cancer xenograft model (p<0.0001). When used in combination with Abraxane®, DEP® gemcitabine significantly outperformed a combination of Gemzar® (gemcitabine) and Abraxane (p<0.005).
Pancreatic cancer is a leading cause of cancer death, with a 1-yr survival rate of 20%, and a 5-yr survival rate of only 7%, with current therapeutic approaches (gemcitabine and Abraxane®) having significant bone marrow toxicities. An important attribute of DEP® products is a lack of bone marrow toxicities in both preclinical and clinical studies.
Dr Jackie Fairley, Starpharma CEO, commented: “We are delighted to be progressing yet another internal candidate through development and to have achieved such impressive results in this important cancer type with otherwise limited options for patients.”
DEP® gemcitabine vs Gemzar® alone
DEP® gemcitabine showed significantly enhanced tumour inhibition as compared to standard gemcitabine (Gemzar®) in this human pancreatic cancer (CAPAN-1) xenograft model (p<0.0001; figure 1).
Figure 1: Enhanced efficacy of DEP® gemcitabine, compared to standard gemcitabine, in a human pancreatic cancer model (CAPAN-1)
DEP® gemcitabine + Abraxane® vs Gemzar® + Abraxane® combination
The anti-tumour effect of the DEP® gemcitabine + Abraxane® combination was significantly better than for the Gemzar® (gemcitabine) + Abraxane® combination (P<0.005).
Figure 2: Enhanced efficacy of DEP® gemcitabine + Abraxane®, compared to standard gemcitabine + Abraxane®, in a human pancreatic cancer model (CAPAN-1)
The mouse xenograft study used CAPAN-1 human pancreatic cancer cells and was conducted for Starpharma by an internationally recognised translational cancer group. A xenograft study uses human cancer cells, which are then implanted in a mouse, and is a well‑established means of assessing efficacy of anti-cancer therapies before clinical trials.
Balb/c mice were inoculated subcutaneously with the human pancreatic cancer (CAPAN-1) cells (10 mice/group). Mice were dosed with saline (vehicle), DEP® gemcitabine, standard gemcitabine (Gemzar®) (120 mg/kg) and Abraxane® (40mg/kg) IV on days 1, 10 and 18.
Tumours were measured twice weekly using electronic callipers. Tumour volume (mm3) was calculated as length (mm)/2 x width (mm)2. Tumour growth inhibition data was analysed in GraphPad Prism and statistical analysis of treatment groups v vehicle control was one-way ANOVA with Dunnets multiple comparison test. Statistical analysis between different groups was conducted via a one-way ANOVA with Sidaks multiple comparison test. The tumour volume data represent the mean ± standard error of the mean (SEM). Note: If error bars do not display on the graphs, they are not visible because they are shorter than the height of the symbol.
About Gemzar® (Gemcitabine)
Gemzar® (gemcitabine) is a chemotherapy drug used to treat cancer of the pancreas, bladder, ovary and breast, and non-small cell lung cancer. Gemcitabine is used as a first-line treatment alone for pancreatic cancer, and in combination with Abraxane® for the treatment of metastatic Adenocarcinoma of the pancreas. Gemcitabine also has a role in the treatment of metastatic bladder cancer, advanced or metastatic non-small cell lung cancer, ovarian cancer and breast cancer. Myelosuppression is the principal dose-limiting toxicity with gemcitabine.
About Starpharma’s DEP® platform
Starpharma’s internal pipeline includes a number of pre-clinical DEP® candidates, including DEP® gemcitabine, as well as three clinical stage assets - DEP® docetaxel, DEP® cabazitaxel and DEP® irinotecan. A fourth DEP® drug, DEP® AZD0466 (AstraZeneca’s Bcl2/xL DEP® program), is expected to enter the clinic later this year.
 For intellectual property reasons, doses of DEP® gemcitabine are not disclosed