Human Genome Sciences, Inc. has reacquired rights to the TRAIL receptor antibodies HGS-ETR1 (mapatumumab) and HGS-ETR2 (lexatumumab) from GlaxoSmithKline (GSK), in return for a reduction in royalties due to HGS if Syncria (albiglutide) is commercialised. HGS is developing its TRAIL receptor antibodies for the treatment of a broad range of cancers, and announced today that it plans to initiate its third randomized phase II chemotherapy combination trial of HGS-ETR1 by mid-2008 in patients with hepatocellular cancer.
"As our phase III products near commercialization, we are investing strategically to bring our next products forward," said H. Thomas Watkins, president and chief executive officer, HGS. "We are building our oncology portfolio around our leading expertise in the apoptosis pathway. We have added IAP inhibitors, which are highly complementary to our TRAIL receptor antibodies. We have initiated new chemotherapy combination trials of HGS-ETR1, and we have now reacquired the rights to our TRAIL receptor antibodies."
The GSK rights to the TRAIL receptor antibodies resulted from a June 1996 agreement under which HGS granted a 50/50 co-development and co-promotion option to GSK for certain human therapeutic products that complete phase IIa clinical trials. In exchange for reacquiring the rights to its TRAIL receptor antibodies, HGS has agreed to a reduction in the royalties to which it is entitled from GSK if Syncria is commercialised.
The fees and milestone payments due to HGS under the original Syncria agreement, some of which have already been received, could amount to as much as $183 million and remain unchanged in the amended agreement. Syncria, a novel long-acting form of GLP-1 (glucagon-like peptide-1), was created by HGS using its proprietary albumin-fusion technology. GSK has exclusive rights to develop and commercialize Syncria, and is developing it for use in the treatment of type 2 diabetes. HGS believes it is possible that GSK will reach a decision in 2008 regarding whether to advance Syncria to phase III development.
"We view our oncology portfolio as the cornerstone of our mid-stage pipeline, and as a key driver of future growth beyond the launch of our late-stage products," said Barry A. Labinger, executive vice president and chief commercial officer, HGS. "Reacquiring the rights to our TRAIL antibodies gives us the opportunity to drive and advance this growing program. We will continue to explore the possibility of bringing in additional new products, as well as forming new partnerships to add expertise and near-term financial resources in support of our pipeline."
HGS reported that a 2002 agreement with the Pharmaceutical Division of Kirin Brewery Company, Ltd. for joint development of antibodies to TRAIL receptor 2 has also been terminated.
HGS-ETR1 is the most advanced of any product in development that targets the TRAIL apoptosis pathway. HGS has advanced HGS-ETR1 to a proof-of-concept phase consisting of three randomized phase II chemotherapy combination trials to evaluate its potential in the treatment of specific cancers:
HGS has completed the enrolment and initial dosing of 105 patients in a randomized phase II trial of HGS-ETR1 in combination with Velcade (bortezomib) in advanced multiple myeloma, and expects to have data available in the third quarter of 2008. In December 2007, HGS initiated dosing of approximately 105 patients in a randomised phase II trial of HGS-ETR1 in combination with paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer, and expects to have data available in 2009.
HGS also announced its plans by mid-2008 to initiate a randomised phase II trial of HGS-ETR1 in combination with Nexavar (sorafenib) in hepatocellular cancer. The study in hepatocellular cancer will begin with a safety lead-in to assure the safety of this combination therapy in patients with hepatocellular cancer who are infected with hepatitis C.
HGS expects to initiate a phase I clinical trial of HGS1029 by mid-2008 and plans to develop its trail receptor antibodies and IAP inhibitors in combination with one another and in combination with other therapeutic agents.
HGS-ETR1 and HGS-ETR2 are agonistic human monoclonal antibodies that directly induce cancer-cell death by specifically binding to and activating the proteins known as trail receptors 1 and 2, respectively. Using genomic techniques, HGS originally identified the trail receptor 1 and 2 proteins. HGS is developing its trail receptor antibodies as potential treatments for a broad range of cancers.