Immunotherapy is in midst of a boom with nearly double the drugs over the last 2 years, more trials than ever before, and a huge investment from the biggest pharmaceutical companies across the globe.
The landscape of immuno-oncology discovery has evolved since 2017, as the number of targeted agents has significantly risen, according to a new analysis conducted by the New York-based Cancer Research Institute and published in Nature Reviews: Drug Discovery.
Patients will clearly benefit from the research – but whether it will totally revolutionize survival against the “emperor of all maladies” remains to be seen, Shridar Ganesan, MD, PhD, told CancerNetwork.
“It's not quite clear whether the new drugs and combinations will only make immune therapies more effective in the cancer types already known to be sensitive to this approach – say, melanoma and lung cancer – or if these approaches will now be effective in cancers such as pancreas cancer, that have little benefit from current immunotherapies,” said Ganesan, the associate director for the Translational Science Section, chief of molecular oncology, and Omar Boraie Chair in Genomic Science Professor of Medicine at the Rutgers Cancer Institute of New Jersey, who was not involved in the work.
The survey by the Cancer Research Institute was conducted in August. It follows a similar survey conducted in September 2017.
Over that time, the number of active drugs in development has grown by more than 90%—from 2,030 in 2017 to 3,876 more recently.
The biggest increase was cell therapy, with 797 new drugs in the pipeline.
Drugs in the pipeline are the subject of 5,166 active clinical trials. The majority of those testing programs are focused on the T-cell-targeted immunomodulators, with 3,428 active trials designed to evaluate just 212 compounds in that class of therapies, according to the findings.
The number of targets for immunotherapies has also ballooned, growing from 263 to 468 over the last 2 years – an increase of 78%.
Ten of the specific immunotherapy targets made the list in both 2017 and 2019: CD19, PD-1, PD-L1, CTLA-4, GHER2, HPV, IDO1, NY-ESO-1, CSF1R, and STAT3.
Of the 2019 list, the biggest gains in the amount of research were made on CD19 and BCMA.
Of particular note is a gradual shift in the research priorities, even over just 2 years. Non-specific tumor-associated antigen (TAA) has actually seen a significant decrease in active pipeline drugs, from 265 in 2017 down to 211 this year. That shift comes with a large increase of new targeted agents such as T-cell immunomodulators, other immunomodulators, and cell therapies.
The United States leads the way, with 1,837 active drugs (47% of the whole pipeline). The next leader is China, which has companies accounting for 614 agents (16% of the pipeline). But the United States has a widely-spread distribution between T-cell-targeted immunomodulators, other immunomodulators, cell therapies, and cancer vaccines, as well as the oncolytic virus and CD-3 targeted bispecific antibody research. But the Chinese focus is predominantly on cancer vaccine development, according to the findings. The United Kingdom and Germany are a distant third and fourth, with 193 and 153 immunotherapy agents in development, respectively.
Decades have passed since the first attempt at evaluating immunotherapies, with the first monoclonal antibodies developed in the 1970s, and the testing of the cytokine interleukin-2 molecule in some cancer cases in the 1980s.
But the sequencing, and better understanding, of the human genome has since created a whole new cancer treatment and research landscape in the 21stcentury, Ganesan said.
He added that the science still has to determine whether the knowledge of the deeper dive into DNA will produce incremental returns, or huge strides forward toward treatments affecting many more patients. For instance, initially huge successes in chemotherapies and even diabetes drugs were followed by refinements that led to gradual improvement.
“The big advance was the fact that these things work – and the first and second generations were very good,” said Ganesan. “When the next-generation agents come along, how much more bang for the buck are we going to get? Are they going to lead to incremental benefit, or a true leap forward?”
But having so much scientific endeavor aimed at this promising line of inquiry can only benefit clinical outcomes, he added.
“Increased research is good. Whether we get new classes of drugs – or just better old classes – is not clear,” said Ganesan. “Either way, it’s going to be good, because it will benefit our patients, but I’m not sure where we are.”
Yu JX, Hubbard-Lucey VM, Tang J. Immuno-oncology drug development goes global. doi: 10.1038/d41573-019-00167-9.