OSLO, Norway—In an unusual approach to a collaborativeannouncement, Clavis Pharma ASA, a Norwegian cancer drug development company,"is pleased to note" that Clovis Oncology, its partner in the development andcommercialization of Clavis Pharma drug candidate CP-4126, and Ventana MedicalSystems Inc. have entered into an agreement to develop a companion diagnosticto CP-4126 for clinical and commercial use based on the hENT1 transporter.
Both Clavis and Clovis are good-natured when asked if theirvirtually identical names stem from an underlying or preceding relationship,and explain the situation is pure coincidence. But Ventana Medical Systems,characterized by Clovis President and CEO Patrick Mahaffy as one of the world'sleaders in developing tissue-based diagnostics, was in touch with both partnersindependently prior to the deal being struck.
"We were looking at a hENT1 diagnostic before the Clovisagreement," says Jan Alfheim, Clavis' chief business officer, "and had starteddiscussions with Ventana. Clovis agreed that they were a good choice, so welicensed the hybridoma to Clovis to develop the diagnostic."
Clovis will seek regulatory approval for the therapeuticmolecule, while Ventana will do the same for the companion diagnostic. "If weare both successful," says Doug Ward, vice president and general manager oftranslational diagnostics at Ventana, "Clovis will be responsible forcommercialization of the product and Ventana the test."
The companion diagnostic is being developed to identifypancreatic cancer patients with low-level tumor expression of hENT1, the humanequilibrative nucleoside transporter protein. Ultimately, the use of a hENT1companion diagnostic will enable oncologists to identify patients who may showa significant benefit from treatment with Clavis Pharma's CP-4126. The hENT1transporter plays a crucial role in the uptake of cytotoxic nucleoside-baseddrugs and its low level or absence has been correlated to a poor clinicaloutcome to treatment with drugs such as gemcitabine and cytarabine.
Clavisquotes figures that indicate pancreatic tumors in up to two-thirds of patientshave low levels of hENT1 on the tumor cell surface.
CP-4126, and other drug candidates in Clavis Pharma'sportfolio, has been developed using its proprietary Lipid Vector Technology(LVT), which enables the compound to enter cancer cells independently of hENT1.
CP-4126 is an LVT form of gemcitabine, the current standard treatment foradvanced pancreatic cancer, and which is also used in combination with otherchemotherapy agents for the treatment of other cancers, including ovarian,non-small cell lung and breast cancer.
CP-4126 is a novel, patented, lipid-conjugated form of thewell-established cancer drug gemcitabine (Gemzar) that has the potential toimprove treatment outcomes in patients with pancreatic cancer as other solidtumors that have low levels of hENT1. The drug
will be directly compared to gemcitabine in aninternational, randomized, controlled trial in patients newly diagnosed withmetastatic pancreatic cancer. The study will enroll approximately 250 patients,randomized between gemcitabine and CP-4126, and measure overall survival (OS)in prospectively defined hENT1-low patients as the primary endpoint. Expressionof hENT1 in tumor tissue will be measured during the trial and patientscategorized into hENT1-high or hENT1-low groups prior to final analysis. Thisstudy is a prospective test of two hypotheses: (1) that low pancreatic tumorhENT1 expression is associated with poor outcome after gemcitabine therapy, and(2) that CP-4126 has superior efficacy (measured by OS) in hENT1-low patientscompared with gemcitabine. This trial will commence enrollment in the secondquarter of 2010, and data from the trial are expected in the first half of2012.
Approximately 37,000 new cases of pancreatic cancer wererecorded in the United States in 2007. The one- and five-year overall survivalrates are estimated at 23 percent and 4 percent, respectively. The majority of patients are diagnosedwith locally advanced (unresectable) or metastatic disease. Median overallsurvival in these advanced patients is four to 10 months.
According to Ward and Mahaffy, no downstream collaborationsare contemplated at this time, but Ward adds that personalized healthcare is afocus for all three companies and they "all appreciate the importance of thistargeted therapy approach."