March 1, 2007 (Vol. 27, No. 5)
With Five Major Players, Therapeutic Vaccines Could Transform Medical Care
Over the past few years, there has been a surge of interest in vaccines. Market growth rates are forecasted at 20% per year over the next five years with the introduction of HPV, influenza, rotavirus, shingles, and meningitis products. R&D investment is growing with the NIH funding a number of bioterrorism projects and the Bill and Melinda Gates Foundation backing a range of vaccines. The worldwide prophylactic vaccine market is expected to reach $15 billion in 2010, up from $10 billion in 2005.
Active immunotherapy, however, has proven to be a difficult development area, with a significant number of clinical failures, primarily for melanoma and pancreatic cancers. But, 2007 could be a pivotal year, bringing new technologies and positive clinical developments for therapeutic cancer vaccine products.
New technologies include DNA and cellular delivery, TLR receptor agonists, and adjuvants. A recent report published by Kalorama Information, “The Emerging Cancer Vaccine Market”, (see BioMarket Trends in the January 15, 2007, issue of GEN) forecasts a $700-million market by 2008 and $8.4 billion by 2012, initially driven by Merck’s (www.merck.com) Gardisil. Highlighted here are five well-funded public companies with proprietary technology and late-stage trials utilizing active immunotherapy along with combination therapy to complement antibody treatment and chemotherapy.
Cell Genesys
Cell Genesys (www.cellgenesys.com) develops cell-based immunotherapies and oncolytic virus-based candidates to treat various types of cancer. Its GVAX products are comprised of tumor cells that have been modified to secret GM-CSF, an immune stimulatory hormone. It has a favorable side effect profile in over 600 patients.
The GVAX immunotherapies include a Phase III product for prostate cancer, a Phase II candidate for resectable pancreatic cancer and acute myelogenous leukemia, and a chronic myelogenous leukemia treatment also in Phase II. Additionally, the company has a strategic alliance with Novartis (www.novartis.com) to develop virus therapies that includes a Phase I program for bladder cancer.
On January 22, the company reported follow-up data from its Phase II trial of GVAX immunotherapy in 60 patients with operable pancreatic cancer after surgical resection of their tumor and adjuvant radiation and chemotherapy. These results show a median survival of 26.8 months. On the other hand, the median survival rate for surgery and adjuvant alone are 17–22 months.
In May 2006, the FDA granted Fast-track designation for this prostate cancer immunotherapy. Results from its Vital 1 and 2 Phase III trails are not expected until 2009.
Richard Smith, Ph.D., an analyst with JPMorgan, expects the launch of GVAX in the 2010 time frame. Needham & Co. also covers the stock with a buy rating.
Coley
Coley Pharmaceutical Group (www.coleypharma.com) is focused on a novel class of drugs for cancers, infectious diseases, and respiratory disorders. It develops proprietary toll-like receptor (TLR) therapeutics. TLR’s are short DNA-like molecules that possess immuno-modulatory properties that direct immune system functions, such as a Th 1 and Th 2 response.
Coley’s non-small-cell-lung cancer (NSCLC) candidate, CPG 7909, entered Phase III trials. On January 22, Coley suspended drug development of Actilon, its candidate for HCV infection, so that it could focus on TLR agonists and antagonists in cancer. In Phase II, CPG 7909 showed antitumor activity in cutaneous T-cell lymphoma, melanoma, and renal cell carcinoma. The drug was well tolerated and offered survival benefit over chemotherapy alone. Coley is partnering CPG 7909, now called PF-3512676, with Pfizer (www.pfizer.com) for NSCLC and breast cancer.
The company’s VaxImmune product is a TLR 9 agonist that enhances antibody levels and killer T-cell immune response. As an adjuvant, it can be used to boost the body’s immune response in cancer and infectious diseases. the VaxImmune product is licensed to GlaxoSmithKline (GSK; www.gsk.com), with four clinical studies underway, and Novartis.
JPMorgan has an overweight rating on the stock.
Dendreon
Dendreon’s (www.dendreon.com) method is to use a selected cancer–related target protein to stimulate a patient’s own dendritic cells, which are then reinfused into the patient to stimulate an immune response.
The company’s primary candidate, Provenge (sipuleucel-T), is an active cellular immunotherapy for the treatment of metastatic androgen-independent prostate cancer. It recently completed Phase III trials. The FDA assigned priority review status to the company’s BLA, which is expected by May 15, 2007, but may be as early as March 29. The BLA submission is based primarily on an improvement in overall survival, reported in the July issue of the Journal of Clinical Oncology.
Dendreon also completed a Phase I evaluation of Neuvenge, an investigative active cellular immunotherapy for the treatment of breast, ovarian, and colon cancers. Phase II should be initiated in 2007.
It has collaborative agreements with Genentech (www.gene.com) for the development of products derived from trp-p8, an ion channel found in prostate cancer cells, and Abgenix/Amgen (www.amgen.com) for the development of Mabs against membrane-bound serine protease, which is implicated in solid tumors.
JMP Securities and Needham have a buy rating on the stock.
Dynavax
Dynavax (www.dynavax.com) has a portfolio of immunotherapeutic products in development to treat allergies, infectious diseases, and cancer. Analogous to the Coley platform, it utilizes immunostimulatory sequences (ISS ) or TLR 9 agonists, which act upon dendritic cells to reprogram the immune system to fight disease.
Although the major focus of the company is its Phase III evaluations of a ragweed allergy immunotherapeutic and a Hepatitis B vaccine, it also has a non-Hodgkins lymphoma (NHL) and colon cancer program. The ISS technology is in a Phase II trial for NHL with Rituximab. The primary objective is to assess the proportion of patients without disease progression after one year of initiating therapy. In December 2006, Dynavax initiated a Phase I trial of its TLR 9 agonist in combination with a standard chemotherapy regimen for metastatic colon cancer.
Zack’s Equity Research has a buy rating.
Vical
Vical (www.vical.com) is a long-term, major player in the imunotherapeutics area, with DNA delivery technologies for infectious diseases and cancer where the expressed protein is an immune system stimulant.
Allovectin is a plasmid/lipid complex containing DNA sequences encoding the MHC-I antigen that is injected directly in to tumor lesions in order to stimulate an immune response against the tumor. Allovectin-7, a cancer immunotherapeutic, recently commenced a Phase III trial as a first-line therapy in chemotherapy–naive patients with recurrent stage III or IV metastatic melanoma.
Vical is also partnered with Merck on a HER-2 and CEA antigen in Phase I studies for breast, colorectal, ovarian, or non-small-cell-lung cancer.
Rodman & Renshaw has coverage of the stock with an outperform/speculative rating.
Another company that has active products in clinical development for cancer is privately held Endocyte (www.endocyte.com). It has a receptor-based technology that targets tumor cells using vitamin folate delivery without damaging normal cells. Endocyte has an expanding pipeline in cancer with two clinical programs: EC17 for metastatic and renal cancer and EC145 for folate receptor positive cancers.
Bristol-Myers Squibb(www.bms.com) licensed the folate targeting technology for a future cancer clinical development program.
Two other public companies with cancer vaccines in clinical development are Geron (www.geron.com) with its telomerase platform and Favrille (www.favrille.com) with Favid, a B-cell NHL immunotherapy in Phase III.
A September 2006 report by Cole Werble (Windhover Information), “Vaccines Enter the New Age of Adjuvants”, expects adjuvant-enhanced products will revolutionize the vaccine field, including candidates from some of the above companies working on immunostimulants.
GSK has a major investment in MPL, a detoxified bacterial lipopolysaccharide, combined with QS21 (from Antigenics) in a compound called AS04. This adjuvant is expected to be in the GSK HPV product, Cervarix, expected in a year or so.
Adjuvants can also confer a proprietary position when formulated with vaccines as they offer product differentiation because of their unique chemical structure and immune system activity.
