The cadre of speakers extolling the virtues of therapeutic cancer vaccines at the recent “World Vaccine Congress” in Lyon, France, included Vincent Brichard, M.D., Ph.D., vp, cancer immunotherapeutics, GlaxoSmithKline Biologicals (www.gsk-bio.com). “Many would say that therapeutic cancer vaccines have experienced 20 years of failure, but I would say it has been 20 years of valuable learning that we are now ready to build on,” said Dr. Brichard.
Therapeutic cancer vaccines, a broad term for a DNA-, cell-, or protein-based drug designed to stimulate the immune system to initiate a cytotoxic reaction against cancer cells, look to be enjoying renewed interest, and Jean-Yves Bonnefoy, Ph.D., vp of R&D at Transgene (www.transgene.com), explained why.
“Investment in therapeutic cancer vaccines is being buoyed along by the market success of prophylactic cancer vaccines such as Merck’s Gardasil and GSK’s Cervarix. This year, TG4001, our cervical cancer vaccine, was licensed by Roche, and Oxford Biomedica’s TroVax renal cancer therapy was snapped up by sanofi-aventis.
“This is a sea change from the past five years when many big pharmas wouldn’t touch therapeutic cancer vaccines because they believed the vaccines didn’t actually work.” Despite the newfound optimism by big pharma, the first approval of a therapeutic cancer vaccine remains elusive.
In the past decade, therapeutic cancer vaccines have been developed mainly by small biotechs that were so strapped for cash they ran short trials to generate rapid results. This led to many cancer vaccines being developed to treat melanoma, pancreatic, or prostate cancer.
These diseases, however, are capable of rapid replication, and disease progression can be recorded before an effective immune response is generated so it is difficult to tell if the vaccine is working using disease progression as a clinical endpoint.
Dendreon (www.dendreon.com) typifies this tale, but its results also underscore the promise of cancer vaccines. The company’s failure to gain regulatory approval this year for sipuleucel-T (Provenge), its autologous-blood, antigen-presenting cell therapy to treat prostate cancer, has been well publicized.
“It has been a roller-coaster ride this year as our BLA for Provenge has been under review,” said David Urdal, Ph.D., CSO of Dendreon. “Provenge just missed its primary endpoint, time-to-disease progression, but it demonstrated a survival outcome in a double-blind, randomized, controlled trial that favored Provenge over placebo. Men assigned to the Provenge arm had a median survival of 4.5 months longer than men assigned to the placebo arm. There was a 41 percent overall reduction in the risk of death with Provenge.
“We learned in this trial that progression of metastatic, androgen-independent prostate cancer is much more rapid than we thought (eight to ten weeks), and measuring time-to-disease progression with a drug that needs time to mount an immune response can be challenging.” Dr. Urdal noted that in contrast, survival is measured in months and may be the best endpoint to use for these types of agents.
“The other useful information we discovered is that patients given Doxitaxel chemotherapy after Provenge treatment may also have better survival rates, so Provenge could be an important new tool for improving the effectiveness of Doxitaxel.
“As Provenge is well tolerated and shows a survival outcome in the studies we submitted in our BLA, the FDA will allow us to submit survival-rate data from our other ongoing Phase III study to amend our BLA and provide additional evidence in support of our efficacy claim,” Dr. Urdal concluded. “We’ll have our first opportunity to see interim data in 2008, so we remain hopeful that Provenge could still be the first therapeutic cancer vaccine approved.”