Response Genetics announced this week that it has begun gene-expression screening studies for a Phase III trial of GlaxoSmithKline's investigational MAGE-A3 antigen-specific immunotherapeutic for non-small cell lung cancer.
GSK is studying the drug as an adjuvant therapy in MAGE-A3-positive patients with stage IB, II, or IIIA NSCLC. Approximately 35 percent to 50 percent of early NSCLC patients express the MAGE-A3 tumor-specific antigen.
Response Genetics said it will perform the assays in formalin-fixed paraffin-embedded tissue, but declined to discuss the collaboration in greater detail.
GSK has begun recruiting patients for the Phase III trial to evaluate its drug in MAGE-A3-positive patients. The company aims to recruit approximately 2,270 patients with stage IB, II, or IIIA resected NSCLC, for the randomized, double-blind, and placebo-controlled MAGRIT trial. The primary endpoint of the trial is disease-free survival.
Garry Daniels, GSK Bio’s director of global product communications, told Pharmacogenomics Reporter over e-mail that only patients expressing MAGE-A3 on their tumor will be eligible for this therapy and could potentially respond to treatment with ASCI MAGE-A3. For this reason, a commercial diagnostic to identify the appropriate patient population may be necessary as a companion to GSK’s treatment. However, neither GSK, nor Response Genetics, discussed any plans to develop a companion diagnostic for this indication.
“Cancer cells not expressing MAGE-A3 at their cell surface can not be targeted by the immune response following the administration of this antigen-specific (Mage-A3) immunotherapy,” Daniels wrote in an e-mail.
“The principle behind ASCI is that any cancer is associated with an antigen that is displayed on the surface of its cells and that the ASCI will target only the antigen that is on the cancer cell,” Daniels added. “It is envisioned that as a result of stimulation of the immune system with ASCI, the immune system will only react to the cancer cell that displays the antigen and will have no effect on the normal cells.”
From SEC filings, it appears Response Genetics’ current collaboration with GSK is part of ongoing discussions between the companies regarding genetic-testing services.
In an December 2006 agreement penned with GSK Bio, Response Genetics was hired to provide genetic-profiling services on cancer specimens provided by GSK Bio. This agreement extends to Dec. 31, 2010, and Response Genetics expects to garner at least $7.3 million for its efforts.
Response Genetics did not recognize any revenue from this agreement in 2006, but saw $330,039 during the three months ended Sept. 30, 2007.
One of the company’s aims is to “produce commercially viable assays used in the validation of genetic markers for pharmaceutical companies.” It is unclear if this collaboration with GSK will produce a diagnostic kit.
The two companies also have a separate agreement started in January 2006, in which Response Genetics will profile the expression “of various genes from a range of human cancers” for GSK. In addition to receiving payment for the services provided, GSK will make minimum annual payments to Response Genetics and meet minimum annual assay testing requirements over a three- year period ending January 2009.
The collaboration is slated to expire in January 2009, at which point Response Genetics is expected to pocket a minimum of $6.5 million. Response Genetics, so far, has earned approximately $3 million in total revenue from the deal. Once the agreement expires, GSK has the right to extend the agreement twice for one-year periods.
Response Genetics, which performs pharmacogenetic testing of clinical trial specimens for pharmaceutical companies, has licensed technology for extracting mRNA from FFPE tumor specimens from the University of Southern California. Additionally, the company, based in Los Angeles, holds a non-exclusive license to use Roche Molecular Systems’ PCR, homogenous PCR, and RT-PCR technologies.
In a presentation last year, Response Genetics said that its methodology for rapidly developing diagnostics involves micro-dissection of the FFPE tumor, followed by RNA extraction, and then analysis by either Applied Biosystems’ Taqman RT-PCR technology or genome-wide analysis on microarrays.
It is unclear whether its collaboration with GSK is only for the analysis of clinical samples or if it will lead to the development and commercialization of a companion diagnostic.
According to GSK’s Daniels, the agreement with Response Genetics is for the duration of the MAGRIT study in NSCLC only. However, that doesn’t necessarily stop Response Genetics from developing a MAGE-A3 diagnostic and selling it to GSK or from even marketing the test on its own.
In fact, a diagnostic may be critical to the commercial success of GSK’s MAGE-A3 ASCI, since in order “to be eligible for this therapy, patients need to be screened and their cancer cells to be found positive for the expression of MAGE-A3,” according to Daniels.
A filing with the Securities and Exchange Commission on Sept. 30, 2007, sheds additional light on Response Genetics’ strategy. The structure of a 2004 collaboration with Roche suggests that Response Genetics aims to commercialize diagnostic test kits out of its collaboration with pharmaceutical companies for genetic testing services.
Response Genetics’ agreement with Roche to “produce commercially viable assays used in the validation of genetic markers for pharmaceutical companies.” The deal gave Roche rights to the pre-diagnostic assays that Response Genetics develops “in the course of using its RNA-extraction technologies to provide testing services to pharmaceutical companies and to produce diagnostic kits that can be sold commercially to those pharmaceutical companies.”
In addition to its collaborations with GSK and Roche, Response Genetics has a deal with ShanghaiBio Corporation that grants the Chinese firm an exclusive license to provide services in China using its RNA-extraction technologies. On its website, ShanghaiBio claims that it “is the only CRO in China utilizing their patented technology to extract RNA from formalin-fixed, paraffin-embedded clinical trial samples.”
Last July, Response Genetics penned a deal with the University of California, San Francisco, to develop diagnostics for pancreatic cancer. Around the same time, Response Genetics netted a deal with Hitachi Chemical in which the Japanese diagnostics manufacturer will use the company’s technologies to extract genetic information from FFPE tissue samples collected in Southeast Asia, Australia, and New Zealand.