Aduro BioTech licensed GVAX Pancreas and Prostate cancer vaccines from BioSante Pharmaceuticals in exchange for milestone and royalty payments. Aduro also has an option to additional GVAX cancer vaccine indications.
GVAX was initially developed by Cell Genesys but suspended in October 2008 after two separate Phase III studies failed. By December 2008, Takeda pulled out of the license agreement it had entered in April 2008. In June 2009, BioSante paid $38 million for Cell Genesys, gaining financial resources that would help the company’s focus on women’s sexual health and stating that GVAX development would be evaluated.
Under its new license arrangement, Aduro will develop the GVAX candidates in combination with its vaccine platform based on Listeria monocytogenes (Lm). Aduro initially plans on developing a sequential vaccine regimen for the treatment of pancreatic cancer using GVAX Pancreas and its lead candidate CRS-207.
CRS-207 has been engineered to express the tumor-associated antigen mesothelin. It has been evaluated in a Phase I trial involving 17 end-stage patients with cancers known to express mesothelin: mesothelioma, non-small-cell lung, ovarian, and pancreatic. Analysis after the completion of the trial revealed a mesothelin-specific T-cell response in multiple patients, according to Aduro. Despite an expected survival of 3–5 months for all subjects, 6 out of 17 lived 15 months or longer, the firm adds.
GVAX Pancreas has been evaluated in more than 120 patients and shown to be able to induce mesothelin-specific T cell responses, Aduro notes. The GVAX cancer vaccines are based on human cancer cell lines that are genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune-stimulatory cytokine.
Aduro has found sequential administration of GVAX Pancreas followed by CRS-207 to be synergistic in mouse models, demonstrating tumor-specific T-cell and antitumor responses. Based on these results, Elizabeth Jaffee, M.D., and Dung Le, M.D., of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, included three pancreatic cancer patients in the CRS-207 Phase I clinical trial who had previously received GVAX Pancreas as part of separate clinical trials. All three late-stage patients who received sequential therapy lived 15 months or longer.
Aduro expects to initiate a Phase II trial in the fourth quarter of this year and to enroll a total of 90 late-stage pancreatic cancer patients. “The synergy from the sequential administration of GVAX Pancreas and CRS-207 has the potential to significantly extend and improve the lives of a patient population where progress has historically been measured by an extra weeks of survival,” says Stephen Isaacs, chairman and CEO of Aduro BioTech.
During Cell Genesys’ Phase III study of GVAX Prostate, back in August 2008, more deaths were found in the GVAX treatment arm compared to those getting Taxotere plus prednisone. In a routine safety review the company’s Independent Data Monitoring Committee (IDMC) noted that 67 deaths occurred in the GVAX plus Taxotere treatment arm and 47 deaths occurred in the control arm. A specific cause for this imbalance has not been reported.
Cell Genesys then inspected a second Phase III study with GVAX in prostate cancer, called Vital-1. The trial was designed to compare GVAX as a monotherapy to Taxotere chemotherapy plus prednisone in earlier stage hormone-refractory patients with metastatic disease. By October 2008, Cell Genesys decided to halt VITAL-1 reportedly because it was determined to have less than a 30% chance of meeting its primary endpoint.
The company was forced to reduce its staff, and Takeda subsequently exited its partnership with Cell Genesys covering GVAX. The company had paid $50 million up front and agreed to milestones totaling up to $270 million. BioSante finally picked up Cell Genesys, but in-house development has stayed focused on its core competence of female sexual health.
BioSante’s lead product is LibiGel®, a transdermal testosterone gel in Phase III development for the treatment of female sexual dysfunction. The company’s first FDA-approved product is Elestrin™, an estradiol gel indicated for the treatment of hot flashes associated with menopause. It is marketed in the U.S. by Azur Pharma. BioSante’s other products are Bio-T-Gel™, a testosterone gel for male hypogonadism licensed to Teva Pharmaceuticals, and an oral contraceptive in Phase II development.