QLT begins pivotal phase III clinical program for multi-drug resistance in non-small cell lung cancer patients
cnw
First patient enrolled with tariquidar in large multi-centered clinical
program
VANCOUVER, June 28 /CNW/ - QLT Inc. (NASDAQ: QLTI; TSE: QLT) announced today that it has begun patient enrollment for two phase III clinical trials using tariquidar as an adjunctive treatment in combination with first-line chemotherapy for non-small cell lung cancer (NSCLC) patients. Tariquidar was in-licensed from Xenova Group plc (NASDAQ NM: XNVA; London Stock Exchange: XEN) for the development and marketing rights in North America in August 2001.
Approximately 1000 patients will be enrolled in two randomized, multi- centered, placebo-controlled trials using tariquidar in combination with two of the most commonly used chemotherapy regimens (paclitaxel plus carboplatin or vinorelbine alone). The trials will be conducted at roughly 100 centers located throughout North America and Europe. The trials are designed to demonstrate the ability of tariquidar to enhance the efficacy of chemotherapy agents. This occurs by preventing or overcoming resistance due to overexpression of P-glycoprotein (P-gp), a membrane protein that pumps chemotherapeutic agents out of cancer cells. Overall survival is the primary end-point in both trials.
"We are extremely pleased to begin the phase III trials for tariquidar on time and to have reached another critical milestone in our development pipeline," said Paul Hastings, president and CEO of QLT. "We believe tariquidar has the potential to be QLT's next big success story, following in the footsteps of Visudyne(R)."
"This is the first time a P-gp inhibitor has been investigated with the standard dose of chemotherapy in a phase III randomized trial," said Mohammad Azab, Senior Vice President, Clinical Research and Medical Affairs at QLT. "With third generation products such as tariquidar, we are able to avoid using a reduced dose of chemotherapy in the treatment regimen."
An interim analysis is planned for mid-2003 in order to mitigate the financial risk of the program. Upon successful completion of the phase III program, it is anticipated that QLT will file for approval of tariquidar in North America for use in combination with first line chemotherapy in advanced NSCLC in 2005. NSCLC is the first of several indications for which tariquidar will be investigated. QLT is also currently conducting a phase IIb trial with tariquidar in patients with refractory breast cancer at the University of Texas MD Anderson Cancer Center.
"There is increasing evidence of the rationale of this approach to the treatment of non-small cell lung cancer. For example, in one independent study, patients who were P-gp positive had a significantly shorter survival time than patients whose tumors were P-gp negative," said David Oxlade, chief executive of Xenova. "Together with our partner, QLT, good progress has been made in the 10 months since the signing of our license agreement and we are pleased that tariquidar has entered clinical registration studies on schedule."
The successful result of three separate phase IIa tariquidar trials was announced in late 2000/early 2001. The trials demonstrated that the combination of tariquidar with a chemotherapy agent was safe and well tolerated. More importantly, no clinically significant pharmacokinetic interaction was found between tariquidar and the chemotherapy drugs, a problem encountered by previous generation multi-drug resistance (MDR) inhibitors. In the trials, tariquidar was used in combination with three of the most commonly used chemotherapy agents (paclitaxel, doxorubicin and vinorelbine), each of which is known to be affected by this resistance mechanism. This benefit allows the chemotherapy agent to be administered at its full standard clinical dose for optimal efficacy.
At the recent American Society of Clinical Oncology (ASCO) in Orlando, Florida, tariquidar was featured in an oral presentation which outlined its potential as a potent third-generation P-gp inhibitor able to block P-gp in solid tumors, with a reduced propensity to negatively affect the pharmacokinetic profile of chemotherapeutic agents.
About Lung Cancer
In the United States, a total of 169,500 new cases of lung cancer were estimated for 2001, accounting for 13% of cancer diagnoses. Lung cancer is the leading cause of cancer-related deaths in United States, accounting for over 30% of cancer deaths in men and 25% in women. NSCLC accounts for approximately 80% of all lung cancer cases.
About Multi-Drug Resistance and P-gp Inhibition
One of the major barriers to successful cancer treatment is the development of resistance by cancer cells to several drugs used in chemotherapy - a condition referred to as multi-drug resistance (MDR). Tariquidar targets the most common form of this drug resistance through the inhibition of P-glycoprotein (P-gp), a membrane based "pump" that acts to expel the chemotherapy drug from the tumor cell, thereby preventing drug accumulation and inhibiting efficacy. Accumulating evidence indicates that the inhibition of P-gp can improve chemotherapeutic outcomes in several types of cancer.
Unsuccessful clinical trials with earlier-generation modulators of MDR were associated with unpredictable pharmacokinetic interactions, which required chemotherapy dose reductions to avoid excessive toxicity. Tariquidar is not associated with these limitations. In addition, first- and second- generation modulators tested in clinical trials only slowed the rate at which chemotherapy drugs were pumped out of the cell by "blocking" the pump for a short-lived length of time. Normal pump function would then return, and the chemotherapy drug would again be removed from the tumor cell. In contrast, tariquidar is not pumped by P-gp but instead binds with high affinity to P-gp, resulting in long-lasting, specific and effective inhibition of P-gp function.
Multi-drug resistance is a problem for many of the most common cancers and involves some of the most widely administered chemotherapeutic agents. In 2001, these drugs accounted for over 1.6 million office-based administrations by medical oncologists in the U.S., according to IMS NDTI database.
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