Sanofi, Glaxo Pursue Research Despite Risk; No Approvals to Date
Source: Wall Street Journal
By: Malin Rising
09.13.2007
COPENHAGEN -- After more than 20 years of setbacks, research into therapeutic cancer vaccines is starting to show promising results and attract the investments of large pharmaceutical firms. But the field remains risky, and so far no drugs have been approved for use.
About eight million people die from cancer each year, a figure that is expected to rise by 50% to approximately 12 million in 2030, making it the world's largest single killer disease, according to the World Health Organization.
Therapeutic vaccines stimulate the body's immune system to attack cancerous cells and leave healthy cells alive, while more traditional cancer treatments kill both types of cells. Although the vaccines won't prevent cancer altogether, they are expected to be used in addition to radiotherapy, chemotherapy and hormone therapy to prevent cancer relapses.
An estimated $50 billion a year is spent on cancer treatment. With a number of promising cancer vaccines now in late-stage trials, U.S. research firm Arrowhead Publishers expects these drugs could generate annual sales of some $6 billion by 2010.
Paris-based Sanofi-Aventis SA, the world's second-largest cancer-drug company by sales after Switzerland's Roche Holding AG, in March bought the rights to the vaccine TroVax from the U.K.'s Oxford BioMedica PLC for about €518 million, roughly $717 million -- the biggest cancer-vaccine deal so far. TroVax is in Phase III trials for kidney cancer and is being tested in colorectal and prostate cancers.
Phase III clinical trials are the final, large trials measuring a drug's efficiency before it is submitted to authorities for approval. They follow Phase I trials, which investigate the safety of a new drug in a small number of people, and Phase II trials, which evaluate a drug's efficacy in treating a specific condition.
Elsewhere, U.K. drug giant GlaxoSmithKline PLC and Germany's Merck KGaA are going head-to-head to get the first lung-cancer vaccine on the market. Merck KGaA isn't related to Merck & Co., of the U.S.
Glaxo in June said it will recruit more than 2,000 patients for a Phase III study of the lung-cancer vaccine MAGE-A3, which it bought from the U.S.'s Ludwig Institute for Cancer Research in 2000. Merck KGaA also is in the process of recruiting more than 1,300 patients for a Phase III study of its lung-cancer vaccine Stimuvax, bought from Canada's Biomira Inc.
Haakan Mellstedt, a professor in oncological biotherapy at Karolinska Institutet in Stockholm, says the development of vaccines is difficult, expensive and takes time but clinical results are starting to show progress.
"There are possibilities here, and now the big companies are starting to be interested, but they haven't had the courage before because it has been too risky for them," he says.
Unlike other cancer treatments, which can cause hair loss, infections and vomiting, scientists believe the vaccines won't have any notable side effects because very few problems have been reported thus far in trials.
"It is an ideal treatment method for people who feel well, since it is practically without side effects," Mr. Mellstedt says.
Sanofi-Aventis and Glaxo declined to comment on when they expect to file for approval of the vaccines or how long it will take to complete the final trials. Merck said it expects its trial will be finished toward the end of 2011.
In earlier studies, most therapeutic vaccines that showed promising results when tested on animals simply didn't work when tried on humans.
Philippe Monteyne, head of global vaccine development at GlaxoSmithKline, admits cancer-vaccine research hasn't been successful in the past, but "it hasn't been 20 years of failing, but 20 years of learning."
He says early studies of MAGE-A3 showed the drug reduced the risk of cancer reoccurrence by 27%, which prompted Glaxo's large investment in late-stage trials.
"The fact that GSK took the decision to embark on this huge study -- the biggest study ever in the field of lung cancer -- shows how much confidence we have in this approach," Mr. Monteyne says.
Wolfgang Wein, senior executive vice president oncology at Merck Serono, a Merck KGaA division, gives a similarly positive outlook for Stimuvax. He says twice as many cancer patients were still alive after three years of adding Stimuvax to regular treatments, compared with patients only using the regular treatments.
Promising late-stage results also are emerging from biotechnology firms Genitope Corp., Antigenics Inc. and Pharmexa A/S, according to the U.S. information consultancy Windhover Information. While Antigenics is adding more research to an existing request for approval of the kidney-cancer vaccine Oncophage, Pharmexa plans to file for approval of the pancreatic-cancer vaccine GV1001 in late 2009. Genitope expects to present a final analysis of the non-Hodgkin's lymphoma vaccine MyVax in the fourth quarter.
Still, no cancer vaccines have been approved by the U.S. Food and Drug Administration, a key consideration for drug companies seeking approval in countries around the world.
"The cruel reality is that compared with most pharmaceutical areas, this approach hasn't had one approved product," says Florian Shoenharting, co-founder and partner at the biotechnology venture-capital firm Nordic Biotech. It has invested €111.3 million in biotechnology firms in Europe and the U.S. but hasn't invested in cancer-vaccine projects.
Market approval of cancer vaccines has been denied because trials haven't reached their primary targets of slowing tumor growth -- despite indications they could prolong lives -- because additional findings in studies aren't considered valid.
Jeffrey Schlom, chief of the Laboratory of Tumor Immunology and Biology at the U.S. National Cancer Institute in Maryland, says companies need to set survival rates as the primary endpoint of cancer-vaccine trials, rather than reduction of tumor growth, and conduct trials over a longer time period. "Measuring patient survival could take five to seven years, which is expensive, but necessary," he says.