Author: Lori Valigra, Mass High Tech correspondent
Sen. Edward Kennedy’s death two years ago from the deadly form of brain cancer, glioblastoma multiforme (GBM), refocused attention on how slowly treatments have progressed since former President Richard Nixon declared the war on cancer in 1971.
But a new form of treatment that goes beyond oncology drugs and surgery is now coming of age: cancer vaccines. At the recent American Society of Clinical Oncology (ASCO) meeting in Chicago — a major forum for cancer researchers — several companies and research groups reported progress on cancer vaccines, including a New England company with a shot for GBM. Agenus Inc. of Lexington reported its Prophage G-200 almost doubled the longevity of patients with recurring GBM to 11 months. That’s good news to patients with that particularly aggressive form of cancer, which also killed composer George Gershwin and music synthesizer legend Robert Moog.
Vaccines represent a relatively new approach to fighting the spread of cancer, having appeared in the last decade. The basic concept is similar to a vaccine for a disease like measles: an injection in the arm induces an immune response that helps the body fight a particular pathogen, in this case, a cancer. An effective immune response would then shrink tumors and extend lives.
Research and Markets estimates that the relatively new market for cancer vaccines could rise sharply to top $7 billion by 2015. The research company looked at six main categories of cancer vaccines: antigen/adjuvant, DNA, vector-based, tumor cell, dendritic cell, and anti-idiotype.
“Cancer vaccines are some of the most exciting areas of medicine we’ve seen in a while. They have the potential to change the way we treat cancer worldwide,” said Anthony Vasconcellos, president and CEO of InCytu Inc., a Lincoln, R.I., company (see page 8) with a very early stage vaccine that boosts the activity of dendritic cells, which in turn activate the immune system, to target GBM and other cancers. “Instead of circumventing the body’s mechanisms, the vaccines harness them. Cancer vaccines really will change the face of medicine.”
Early cancer vaccines were not potent enough, noted Thomas Davis, MD, senior vice president and chief medical officer at Celldex Therapeutics Inc. of Needham (see page 8), a cancer vaccine spinout of Medarex Inc. of New Jersey (now owned by Bristol-Myers Squibb Co.). Davis said a critical turning point for cancer vaccines was the discovery by Drs. Ralph Steinman and Zanvil A. Cohn at Rockefeller University in New York of dendritic cells, which are pivotal to the immune system. “The cells don’t work well in patients with cancer. There’s still a lot we do not know, but we are getting a better sense of how dendritic cells work and how cancer suppresses them,” Davis said. “We are in the dawning of the vaccine era.”
Garo Armen, CEO of Agenus Inc. (formerly Antigenics), agreed. In the last 12 months, especially, there has been a lot of positive activity with cancer vaccines, he said, pointing to Dendreon Corp.’s Provenge for metastatic castrate resistant (hormone refractory) prostate cancer, which was the first cancer vaccine approved by the U.S. Food and Drug Administration, and Bristol-Myers Squibb’s Yervoy for metastatic melanoma.
“These two vaccines were very important approvals in the last year,” Armen added. “To date oncologists haven’t had many tools other than traditional chemotherapy drugs to treat patients. That improvement would extend life by two to three months at best. Now for the first time we have a different pathway, the immunological pathway, and we have the tools to make it work.” Agenus actually had the first approved cancer vaccine, Oncophage, but that was in Russia to treat kidney cancer patients post surgically and will not be submitted for U.S. approval, he said.
Several other New England companies also are working on cancer drugs, including ONCoPEP Inc. of North Andover, which is developing a vaccine for smoldering myeloma (a precursor to multiple myeloma). Celldex Therapeutics Inc. (formerly Avant Immunotherapeutics Inc.), is making a brain tumor vaccine. InCytu’s vaccines are based on intellectual property from Harvard University.
In addition, RNAi-focused biotech firm Alnylam Pharmaceuticals Inc. of Cambridge has a license deal with Australia’s University of Queensland that gives the company access to RNAi intellectual property to develop cancer vaccines. And, RXi Pharmaceuticals Corp. of Worcester presented positive Phase 2 efficacy results at ASCO for its NeuVax peptide vaccine combined with Genentech/Roche’s Herceptin for breast cancer patients. The group of patients treated with the vaccine showed no cancer recurrence for three years, compared to 22 percent recurrence in patients receiving standard care.
BioVex Group Inc. of Woburn perhaps punctuated the value now being placed on cancer vaccine technology when it said in January that it would be acquired by biotech giant Amgen Inc. of Thousand Oaks, CA, for up to $1 billion. The transaction was completed March 4. The company is in a Phase 3 multinational study in metastatic melanoma and a Phase 3 study in squamous cell carcinoma of the head and neck with an oncolytic vaccine called OncoVEX(GM-CSF). The vaccine uses a virus to target and destroy certain cancer cells as well as create an immune response to tackle cancer cells throughout the body.
Melanoma was a hot topic at the ASCO meeting, because the cancer has been tough to arrest. Armen of Agenus said Yervoy in particular was a breakthrough, because it removes the braking system of the immune system and it also potentially could be used for other cancers including lung and prostate.
Bristol-Myers released results at ASCO of a second Phase 3 randomized trial of Yervoy showing it prolonged the lives of patients with metastatic melanoma. The FDA approved Yervoy for patents with unresectable or metastatic melanoma in March 2011.
The Agenus drug for GBM induces an immune response that lets patients fight their own disease, said University of California at San Francisco (UCSF) neurosurgeon Andrew Parsa, MD, who led the G-200 study. Without treatment, he said half of the patients in the trial would have died of the cancer within five to nine months based on historical data. After receiving the vaccine, the median survival for 30 patients who received at least four vaccinations was 11 months. Several have survived for more than a year.
A second objective of the trial was to see if the vaccine could produce an immune response in all patients, and the results showed that it did in every patient in the trial tested to date. This suggests that doctors may be able to extend survival even longer by combining the vaccine with other drugs that enhance this immune response, Parsa said. Some 17,000 Americans are diagnosed with glioblastoma every year, he said, and only 2 percent of them survive longer than five years, even with treatment. Based on the study results, Agenus has started working with UCSF and other experts to design a randomized trial.
“With the recent FDA approvals of Provenge and Yervoy, which both harness the power of the immune system to fight cancer and offer the potential for combination use with other immunological agents, I believe we are entering a new era in the treatment of cancer that could see substantially improved survival rates in patients fighting this disease,” Marcel Rozencweig, MD, acting chief medical officer of Agenus, said in a statement when the data was released.
The future may involve trials combining G-200 with other agents. “G-200 patients aren’t responding to anything. Everything else has failed,” Armen said. “People don’t live with this disease.” He said cancer vaccines have the potential to be the Holy Grail in the treatment of cancer, but for that promise to be fulfilled they must be able to direct the immune system to target a patient’s own cancer and their potency must be improved. Cancer vaccines combined with immune/pathogenesis modulators could enhance activity in late-stage cancers, and G-200 could be combined with Yervoy or other drugs.
Davis of Celldex takes it a step further. “The next generation of vaccines will have multiple targets in them in the same patient,” he said. Celldex’s lead candidate is a vaccine for EGFRvIII-expressing tumors. The company also uses monoclonal antibodies to target dendritic cells, which in turn spark an immune response.
Doris Peterkin, CEO of ONCoPEP (see sidebar), said patients are getting diagnosed earlier and living longer. “There’s a general acceptance in oncology of the value of immunotherapy, but the frustration is how to make it work. We need to understand why certain patients respond and others don’t,” she said. “One drug doesn’t work the same for every patient; it will be the same thing for immunotherapy.” She added that cancer vaccines have improved by leaps and bounds in the past two years, but it’s important to get to an earlier stage of the disease.
Added Davis, “In the first 30 to 40 years of the war on cancer, the most progress was made in understanding what is going on with cancer and the immune system. It will still be many decades before we say we can cure most cancers.”