The H1N1 vaccine has spurred media interest in vaccines, as well as predictions of vaccines for a host of new diseases. According to healthcare market research publisher Kalorama Information's latest research and interviews with industry experts, certain cancers may be added to the list of diseases for which vaccinations will be employed. But this is not a new development. Such vaccines have rather quietly been in development for a decade and an array of products is poised to launch.
Worldwide, cancer affects more than 10 million people each year. Researchers have long struggled to recruit the body's immune system to attack tumors while leaving healthy cells alone. This would offer a huge improvement over existing treatments such as chemotherapy and radiation, which kill healthy and diseased cells indiscriminately and carry harsh side effects. Past attempts to find a simple cancer vaccine have failed, largely because scientists had a crude understanding of the molecular mechanics of the immune system and cancer cells.
DNA Profiling Drives Shift towards Personalized Treatments
But patients will soon benefit from the advances that have occurred in the field of DNA profiling and the emerging field of pharmacogenomics, the analysis of a tumor's specific genetic make-up to potentially guide treatment decisions. Pharmacogenomics is especially important in the treatment of cancer as severe systemic toxicity and unpredictable side effects can interfere with cancer treatments. This new field could soon lead to tailored treatment regimens based on the specific genetic profile of an individual tumor. Eventually, it is likely that physicians will treat tumors based on their genetic make-up rather than their location.
A clear progression in underlying technology platforms can be seen: from early, simple vaccines using inactivated viruses or tumor cells and cell lysates; through to the identification of specific antigens to create more advanced viral vectors, dendritic cells, conjugated vaccines and anti-idiotype vaccines. Among the newer technology types, DNA vaccines and prime-boost technologies can be singled out as two areas of particularly exciting potential, alongside the development of vaccine combinations.
Prophylactic Cancer Vaccines on the Market Today
Cancer vaccines can be separated into two distinct types: therapeutic and prophylactic. There are two prophylactic vaccines that have been licensed by the FDA to prevent virus infections that can lead to cancer. The hepatitis B vaccine, which prevents infection with the hepatitis B virus, an infectious agent associated with some forms of liver cancer; and Gardasil, which prevents infection with the two types of human papillomavirus (HPV) - HPV 16 and 18 that together cause 70 percent of the 500,000 cases of cervical cancer cases worldwide. Gardasil also protects against infection with HPV types 6 and 11, which account for 90 percent of cases of genital warts. Worldwide a few other prophylactic cancer vaccines are available including Gardasil's competition, Cervarix which is available in Europe and was approved for use in the US in October 2009.
Following Gardasil's proven success as the first blockbuster multi-billion dollar preventive cancer vaccine, drug makers are taking notice, promising more cancer vaccines on the horizon against the likes of colorectal, lung, breast and prostate cancers. According to Kalorama, cancer vaccine sales will more than double from $1.8 billion in 2008 to $4.2 billion by 2012. This unprecedented growth is creating countless opportunities for market participants.
Therapeutic vaccines are segmented into two basic types: patient-specific (personalized or autologous) vaccines, created by using the patient's own tissue in the production of an individualized therapy; and non-patient-specific (generalized, or allogeneic) vaccines, which are 'off-the-shelf' mass-produced therapies. Personalized vaccines have been well-represented among the first few therapeutic vaccines to be developed, because they offer the advantages of being formulated specifically for each patient and do not require such an in-depth understanding of the exact antigens involved. However, they present major commercial disadvantages that have limited their uptake: very high cost and low scalability of manufacture, logistical complications, concerns over sterility and a more complex regulatory approval process.
To date, there are no licensed therapeutic vaccines that show overwhelming improvements in efficacy, safety, or cost. However, several treatment vaccines are in large-scale testing in humans and could provide a turnaround for the market.
Therapeutics Vaccines in Development
Several promising vaccines are in late stage development and are preparing for regulatory review in the United States and internationally. Many of the products – including OncoVAX, TroVax, and Lucanix – are already in Phase III development, have orphan drug status, SPA status, or Fast Track status, which promises a bright future for many of these products.
OncoVAX – offered by Vaccinogen, OncoVAX is an active-specific immunotherapeutic for the post-surgical treatment of patients diagnosed with Stage II colon cancer. The product is currently marketed in some European countries, including the Netherlands. OncoVAX is prepared for each patient using the patient's own surgically removed tumor. Upon arrival at an OncoVAX center, the tumor is enzymatically treated, frozen, and irradiated to render the cells non-tumorogenic. The patient receives the first of four vaccinations several weeks after surgery. The vaccine consists of a portion of the tumor cells that has been thawed and combined with a proprietary formulation of Bacillus Calmette Guérin (BCG) that serves as an immunogenic enhancer. This formulation is also used for the second inoculation. The third inoculation and the final booster inoculations are prepared the same way but without the addition of BCG.
OncoVAX is the most advanced cancer vaccine in development today and is currently being evaluated in a Phase III study for stage II colon cancer. Vaccinogen, which acquired OncoVAX from Intracel in 2007, has provided this vaccine to patients with colon cancer in Switzerland in conjunction with surgery. In the U.S., the FDA has granted Fast Track designation and also approved a Special Protocol Assessment. An NDA is expected from the company in 2009 or 2010 and an approval is anticipated by 2011 or 2012. Surgery alone cures approximately 65% of Stage II colon cancer cases. However with this cancer vaccine treatment, the company expects the percentage to increase.
TroVax – Oxford BioMedica's leading cancer immunotherapy product, TroVax is a novel cancer vaccine in clinical development with potential application in most solid tumor types. TroVax delivers a novel proprietary tumor associated antigen (5T4) using a pox virus vector. 5T4 is broadly distributed throughout a wide range of solid cancers and the presence of the 5T4 antigen is correlated with a poor prognosis. The product seems to be effective for all solid tumors where the 5T4 tumor antigen is present. TroVax is currently in Phase II development for colorectal cancer and is also in Phase II trials for prostate cancer, pancreatic cancer, and melanoma.
A phase III trial of TroVax for renal cancer faced a delay in 2008 due to what appeared an inordinate number of deaths during the trial, leading Oxford BioMedica to halt further vaccinations. But on further study, the FDA stated that there is no clear evidence of the deaths being attributable to TroVax. The company announced in September 2009 that the vaccine could still benefit some patients if pre-selected through a blood test.
Lucanix – NovaRx Corporation commenced a Phase III study for Lucanix in July 2008. The trial is designed to evaluate the product's effectiveness against placebo in patients with stage III or stage IV non-small cell lung cancer. NovaRx completed a Phase II study in 2006 which demonstrated a two-year survival rate more than four times that of individuals treated with traditional care plans.
The current phase III study of Lucanix is an international, multicenter, randomized, double-blinded, placebo-controlled study, with an estimated enrollment of 700 patients and a completion date of September 2011.
Though promising, these vaccines will have to overcome a few hurdles, including the reimbursement issue. The real stumbling block in this cancer treatment area is establishing efficacy and safety in these untapped products. Manufacturers must not only demonstrate that new vaccines are superior to other products on the market but also that pharmacogenomics and personalized medicine are worth the anticipated additional cost. There remains overwhelming disappointment for developing companies and an enormous amount of financial risk.