The U.S. Food and Drug Administration (FDA) granted orphan drug designation last week to the immunotherapy vaccine CRS-207, moving it one step closer to changing the way malignant pleural mesothelioma is treated.
CRS-207 is derived from Listeria monocytogenes, a bacterium that causes the serious infection listeriosis. For the vaccine, the bacteria are weakened and genetically modified to produce an anti-tumor response without causing disease.
Early results are impressive.
The vaccine produced a 94 percent rate of disease control, either partial response or stable disease, according to a presentation made at the latest International Mesothelioma Interest Group (IMIG) conference. At time of presentation, estimated progression-free survival was 7.5 months.
“This is an exciting therapeutic avenue that will save many more lives, or at least allow extra quality time for mesothelioma patients,” Dr. Tawee Tanvetyanon, oncologist at the Moffitt Cancer Center in Tampa, Florida, told Asbestos.com. “It is very promising. It could change the paradigm in the management of mesothelioma.”
CRS-207 now is part of a multicenter phase I clinical trial that researchers expect will continue enrolling new patients until the end of 2015. Because the trial still is labeled as investigational research, there is no cost to those enrolling.
Centers conducting the trial today are:
The trial is designed for patients who received no prior therapy and are not candidates for surgery. It will document the safety and efficacy of the vaccine as it navigates slowly through the FDA approval process.
The drug works by eliciting an immune response against the antigen mesothelin, which is present in higher levels on certain tumor cells, including mesothelioma. Doctors deliver the CRS-207 vaccine before the standard chemotherapy regimen for mesothelioma, a combination of pemetrexed and cisplatin.
Side effects have been minimal beyond a mild chilling sensation patients report during the administration of the vaccine.
“We have found that the mesothelioma has shrunk considerably when we checked patients with a CT scan following the vaccine and chemotherapy,” Tanvetyanon said.
He also has seen patients who lost their appetite and 10 to 20 pounds from the cancer suddenly regain their appetite and weight during the course of immunotherapy treatment with CRS-207.
“They recovered their well-being,” he said.
The orphan designation promotes the research and development of treatments for rare diseases like mesothelioma, which is diagnosed in only 3,000 people each year in the U.S.
The designation creates an incentive for pharmaceutical companies, which otherwise would be reluctant to invest time and money into products that would not be widely distributed.
It also provides tax incentives for certain research, and qualifies the developing company for grant funding and limited marketing exclusivity for seven years. CRS-207 previously qualified for orphan drug designation as a treatment for pancreatic cancer.
“This is an important step as we continue to develop CRS-207 for this very difficult to treat cancer,” Dirk Brockstedt, Ph.D., senior vice president of research and development at Aduro Biotech, the pharmaceutical company making the drug and conducting the trial, said in a press release. “We plan to report additional data from the ongoing phase Ib study later this year.”
More than 400 biologic products and drugs for rare diseases have been developed through the orphan drug designation process since the FDA first adopted the incentive in 1983. By contrast, fewer than 10 products came to market in the 10 years preceding start of the program.
Immunotherapy drugs already are proving effective in more common malignancies, including cancers of the lung, skin, colon, breast and prostate. None has yet to be approved for mesothelioma.
Tanvetyanon, like many oncologists, has encouraged patients to at least investigate the possibility of joining a clinical trial.
“You are giving yourself an opportunity to receive cutting edge therapy, which is still not available outside of a clinical trial,” he said. “Immunotherapy is an innovative and, in my opinion, better way to treat cancer. There is no reason why this would not work with mesothelioma.”