Jerusalem, Israel — BioCancell Therapeutics, Inc. (TASE:BICL) today announced
success in meeting the goals of its Phase I/IIa clinical trial of drug candidate BC-819 as a treatment for pancreatic cancer, namely the safety and preliminary efficacy of the product.
Based on the results of the clinical trial, and the results of a successful pre-clinical study announced on October 12, 2010, that examined the sequential administration of BC-819 with FDA-approved drug Gemzar (Gemcitabine) in animals as treatment for pancreatic cancer, BioCancell intends to prepare to apply to the Food and Drug Administration (FDA) to receive approval for an international Phase IIb clinical trial.
The following is a summary of the main results of the clinical trial, including the results of patient examinations, one and three months following the commencement of treatment with BC-819:
1. Primary Endpoint – Drug Safety
The clinical trial included nine patients who each received four treatments over the course of two weeks. Three patients were included in a lower dosage cohort, each receiving 4 mg per treatment, while six others were included in a higher dosage cohort, each receiving 8 mg per treatment. The primary endpoint was the evaluation of the safety of BC-819 (establishing the maximum tolerated dose and whether or not dose-limiting toxicities were encountered). The findings show that no toxicity limited the dose, and therefore the optimal dose was fixed as the maximum dose given in the trial (8 mg).
No patient reported pain or discomfort as a result of the drug.
Throughout the trial, no adverse effects definitely related to BC-819 were reported. One possibly-related adverse event was reported in one patient, with no clinical effects observed.
BC-819 demonstrated an excellent safety profile for use as a treatment for pancreatic cancer in this clinical trial.
2. Secondary Endpoint – Preliminary Efficacy – Tumor Response
Pancreatic cancer is one of the most drug-resistant forms of cancer. A secondary endpoint of the trial was determining the preliminary efficacy of the treatment on the local pancreatic tumor alone (although tumor effect on the overall disease, meaning the local tumor together with the appearance or non-appearance of metastases, was recorded as well). A statistical analysis shows that the higher dosage given in the trial demonstrated greater efficacy than the lower dosage given.
|A.||Within a month from commencement, the local tumor had not increased in size in 8 out of the 9 patients, but rather remained stable in both dosage cohorts.
|B.||Six of the patients examined three months after commencement of treatment showed a reduction in the size of the local tumor. The reduction was significant (30% or more, known as Partial Response**) in three out of six patients of the higher-dose cohort. These three patients also showed no metastatic disease, despite the fact that the clinical trial was aimed at the local tumor only. In addition, it was shown that the effect of the BC-819 treatment was stronger after three months from commencement, than after one month only.|
|C.||In addition to the aforementioned patients displaying a Partial Response, three months after commencement of treatment, three additional patients displayed overall Stable Disease** (stable tumor size and no metastatic disease), despite the length of time that had elapsed. In total, six patients displayed Stable Disease or a significant response after three months from commencement of treatment.|
|D.||A noticeable finding from the tables below is that the higher dosage cohort was characterized primarily by patients displaying significant tumor reduction (30% or more) after three months, as compared to their response (primarily stable disease) after one month.|
|E.||An operation to remove pancreatic tumors (the Whipple procedure) is the best chance for survival a patient can be offered, but most patients are not operable on account of the complexity, location and size of the tumor. Following treatment with BC-819, two patients in the higher dosage cohort that were non-resectable, became resectable as a result of tumor shrinkage. The first showed reduction of 15% in tumor length and had the tumor successfully removed at the University of Maryland Medical Center, Baltimore, MD. The second showed reduction of 52% in tumor length, and was operated upon, but the surgeon halted the operation upon discovery of liver metastases, in order to prevent unnecessary risk to the patient.|
The following tables show the break-down of patient response to BC-819:
Local Pancreatic Tumor Response to BC-819
|4 mg||8 mg|
|Tumor length reduction of 30% or more (Partial Response*)||0 (0%)||3 (50%)|
|Neither Partial Response nor Progressive Disease (Stable Disease*)||2 (67%)||3 (50%)|
|Tumor length increase of 20% or more (Progressive Disease* )||1 (33%)||0 (0%)|
|Total||3 (100%)||6 (100%)|
Overall Disease (Local Pancreatic Tumor & Metastases) Response to BC-819
|4 mg||8 mg|
|Tumor length reduction of 30% or more and non-appearance of metastases (Partial Response*)||0 (0%)||3 (50%)|
|Neither Partial Response nor Progressive Disease (Stable Disease*)||1 (33%)||2 (33%)|
|Tumor length increase of 20% or more or appearance of metastases (Progressive Disease* )||2 (67%)||1 (17%)|
|Total||3 (100%)||6 (100%)|
* In accordance with the internationally accepted Response Evaluation Criteria in Solid Tumors (“RECIST”).
It is common to examine drug combinations for the treatment of cancer, and a combination of BC-819 and Gemzar is designed to reach maximum efficiency in treating a disease with a high level of mortality. As previously reported, pre-clinical testing has shown that in animals treated with the sequence of BC-819 and Gemzar, the volume of tumors shrank significantly, in comparison with the animals treated with Gemzar alone. In addition, there was no appearance of metastases in the animals treated with the sequential administration of BC-819 and Gemzar, while 63% of animals treated with Gemzar alone showed metastatic growths.
As noted above, on the basis of the aforementioned results, BioCancell intends to apply to the FDA to commence a Phase IIb clinical trial of BC-819 in sequential administration of Gemzar, for the treatment of pancreatic cancer.
An “orphan drug” is a drug for a disease that affects a relatively small number of people in a population. In the USA, an orphan drug is defined as one that treats a disease affecting less than 200,000 people each year. In order to encourage the development of drugs for such diseases, benefits and incentives can be granted to the drug developers. The main standard benefit for orphan drugs in the USA is the right to market the drug exclusively for 7 years from the date it is approved. Additional benefits include tax benefits on R&D expenses, and waived FDA fees.
As previously reported, BioCancell has been conducting a Phase I/IIa clinical trial for this application since November 2009, pursuant to an Investigational New Drug Approval from the FDA. The trial is expected to include nine patients, who each receive four treatments, twice per week for two weeks. The University of Maryland Medical Center in Baltimore, and Hadassah, Sheba and Meir Medical Centers in Israel are participating in the trial. Treatments are partially funded by the US-Israel Binational Industrial Research and Development Foundation (BIRD), which approved a grant in the amount of $950,000, or 50% of the predicted expenses of this project.
In January 2010, BioCancell reported completion of the first of two dosage cohorts in the clinical trial, with no treatment-related serious adverse events reported. Following a review of the safety results to confirm that the safety target of the first cohort had been achieved, the clinical monitor of the Clinical Trial approved the commencement of a second dosage cohort, with patients receiving the maximum planned dose of eight milligrams.
This orphan drug approval is in addition to a similar approval of orphan drug status for BC-819 for use in treating ovarian cancer.
BioCancell’s Technology – Patient-Oriented, Targeted Therapy
BioCancell’s technology is both Personal and Targeted. The approach is based on the identification of particular genes that are highly expressed only in tumors (“Target Genes”). The regulatory sequences of these Target Genes are used to drive the expression of a toxin gene exclusively within tumor cells, enabling targeted tumor-cell destruction, leaving normal cells intact. In effect, the plasmid acts as “smart bombs”, activated only inside their targets thus destroying only the cancerous cells, while leaving healthy cells intact.
The patient’s eligibility for the treatment is determined by analyzing the patient’s tumor for the expression of the specific Target Genes. The diagnosis of the expression of the Target Genes are, therefore, a prerequisite for treatment and is made possible through the Company’s proprietary diagnostic technology that enables detection of even a single malignant cell. Only those patients with high expression levels of the Target Genes in their tumor are eligible for treatment with high confidence of success.
The Company has designated two genes as Target Genes – H19 and IGF2.
Discovered by Professor Avraham Hochberg in humans, H19 is an oncofetal gene that encodes RNA (with no protein product) that is expressed at high levels in over 30 types of human cancer tissues, while existing at a nearly undetectable level in the surrounding normal tissues, thus making it an optimal weapon in the fight against cancer.
The gene is expressed abundantly in the human placenta and in several embryonic tissues, but is repressed post-natally and only re-expressed with the appearance of cancer, within cancer cells. Studies show that H19 fulfills an important role in the process of tumorigenesis, and it is thought that the gene enables tumor cells to survive and proliferate under stress conditions.
BioCancell Therapeutics Inc. is a biopharmaceuticals corporation specializing in the development of Patient-Oriented, Targeted Therapy for the treatment of numerous types of cancer. The Company’s proprietary technology constitutes a novel paradigm for the targeted destruction of cancer cells, with no effect on normal surrounding tissue and no observed side effects, allowing for long-term, safe treatment and prevention of cancer.
BioCancell was co-founded in 2004 by Professor Avraham Hochberg, Professor of Molecular Biology at the Hebrew University of Jerusalem, based on technology developed by him over the past 15 years.
BioCancell’s securities are traded on the Tel Aviv Stock Exchange.
This press release contains “forward-looking” statements, including statements with respect to the further development and potential safety and efficacy of BC-819, in the treatment of superficial bladder cancer and BioCancell’s development strategy. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. There are a number of important factors that could cause the results of BioCancell to differ materially from those indicated by these forward-looking statements, including, among others, the risk that the U.S. Food and Drug Administration may require changes to the protocols and informed consents for clinical trials of BC-819, which changes may have a material adverse effect on the timing of, and BioCancell’s ability to conduct, those clinical trials, risks related to the clinical advancement of its BC-819 plasmid, including, but not limited, to the risk that clinical trials for this product candidate may not demonstrate safety and efficacy sufficient to obtain the requisite regulatory approvals or to result in a marketable product and risks related to the potential for others to develop products containing or based on BC-819. BioCancell does not undertake any obligation to update forward-looking statements.
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