Among the commercials for chips, soda and cars, viewers of next month’s Super Bowl LII may also see ads for a surprising new category of products: cancer immunotherapy medicines.
A century ago, surgical removal was the only mainstream option to treat cancer. Radiation therapy and chemotherapy emerged in the middle of the 20th century, adding two more pillars to the treatment map. Yet, only one in three cancer patients in 1970s survived through the first five years of diagnosis. Today, the figure has climbed to 70 percent and is continuing to rise.
As scientists crack the code of cancer biology and genomics, targeted therapy and immuno-oncology (IO) have become the de facto fourth pillar of cancer management that is beginning to overshadow the three conventional pillars. This shift in treatment, and what it means going forward for patients, was the subject of many presentations and discussions at a recent medical meeting, the Society for Immunotherapy of Cancer (SITC) annual conference, held in November of last year. The conference attracted a record number of 2,700 clinicians and scientists hailing from academia, government and industry, up from 800 attendees just five years ago.
Despite the rapid increase of IO as a treatment option, clinicians and researchers are still searching for ways to either fine-tune regimens or explore new avenues to improve outcomes. Not all IO medicines work the same, and there’s still much improvement to be made.
Unlike other approaches, IO harnesses the patient’s own immune system to detect and mount attacks on cancer cells, much like it does bacteria and viruses. There are hundreds of new IO medicines in the clinical trial pipeline1, including:
- Approximately 100 cancer vaccines
- Close to 50 checkpoint modulators
- More than 20 chimeric antigen receptor T-Cell (CAR-T) therapies
- 14 oncolytic virus therapies
The center stage of IO has been dominated in the past five years by checkpoint inhibitors. To evade immune attacks, some cancer cells are coated with checkpoint molecules, which put brakes on killer T cells. Checkpoint inhibitors act by removing these brakes. The first checkpoint inhibitor approved in 2011 is an antibody directed against CTLA-4. Since then, five more inhibitors against PD-1 or PD-L1 have been approved in 15 more indications and counting.
The limelight is swiftly shifting, with two CAR-T cell therapies winning historic FDA nods last year. CAR-T cell therapies fall under the banner of adoptive cell therapy, which involves isolating T cells from the blood, (genetically) manipulating their cancer-killing activity in the lab, and reinfusing the turbocharged T cells back into the patient. The two CAR-T cell therapies approved this year are the first ever to realize the promise of gene therapy in the market, marking the dawn of a new era for the medical field.
Cancer immunotherapies are hitting prime time and captivating public attention. Ads for these medicines are now featured on TV. Yet questions and challenges remain:
- Biomarkers and response rates. Checkpoint monotherapies are not sufficiently active for many patients, benefiting only 1 in 12 patients today2. In a quest to discover effective combinations, the number of combination studies involving PD-1 or PD-L1 inhibitors with other therapies has more than tripled to approach 800 trials in the past two years alone3. How do we define reliable and relevant biomarkers to better guide patient selection, design combination trials, and predict responses?
- Acquired resistance. Some patients who initially respond to therapy will eventually develop resistance. Loss of T-cell function, lack of tumor antigen recognition, and escape mutations in the cancer have been cited as culprits, but little is known. Can medical science leverage other disciplines like math and physics to interrogate the immune system in a more rational, multi-omic way?
- Adverse events. Immunotherapy is uniquely associated with acute toxicities such as cytokine release syndrome, neurological and autoimmune endocrine toxicities. These adverse events can be severe or even fatal. Are healthcare providers equipped to intensively monitor and manage these toxic effects? Can we identify pre-existing risk factors prior to treatment?
- Health economics. Checkpoint inhibitors each bear a list price of $150,000 per year4; combinations charged extra. CAR-T cell therapies are currently marketed at around $400,000 per infusion5,6 without existing CMS code for reimbursement. With value-based reimbursements becoming a recurrent theme, how can we measure and demonstrate value and devise novel payment strategies?
IO as the fourth pillar of cancer therapy is stronger than ever, and it is taking a village to erect it. More than 130 biotechs and 20 pharmaceutical companies are working on IO, and the number of IO alliances have grown from a handful in 2013 to about 60 in 20157.
At Johnson & Johnson Innovation, we strive to fight cancer by bringing together multi-disciplinary approaches that target different aspects of the disease. We believe that ideas and synergies can come from anywhere, and we invite you to join us.
It’s exciting to be working on an area with such promise.
- Pharmaceutical Research and Manufacturers of America, The American Cancer Society Cancer Action Network, 2017. Medicines in Development: Immuno-oncology; http://www.phrma.org/medicines-in-development-immuno-oncology
- MIT Technology Review, 2017. James Allison Has Unfinished Business with Cancer; https://www.technologyreview.com/s/604086/immunotherapy-pioneer-james-allison-has-unfinished-business-with-cancer/
- Plieth J, Elmhirst E. PD-1/PD-L1 Combination Therapies, 2017; www.evaluategroup.com/PD1-2017
- Reuters, 2017. The Cost of Cancer: New Drugs Show Success at a Steep Price; https://www.reuters.com/article/us-usa-healthcare-cancer-costs/the-cost-of-cancer-new-drugs-show-success-at-a-steep-price-idUSKBN1750FU
- Forbes, 2017. Novartis CEO's Dilemma: Is $475,000 Too Much For A Leukemia Breakthrough? Or Is It Not Enough?; https://www.forbes.com/sites/matthewherper/2017/08/30/novartis-ceos-dilemma-is-475000-too-much-for-a-leukemia-breakthrough-or-is-it-not-enough/#1cda322556ec
- Gilead Press Release, 2017. Kite’s Yescarta™ (Axicabtagene Ciloleucel) Becomes First CAR T Therapy Approved by the FDA for the Treatment of Adult Patients With Relapsed or Refractory Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy; http://www.gilead.com/news/press-releases/2017/10/kites-yescarta-axicabtagene-ciloleucel-becomes-first-car-t-therapy-approved-by-the-fda-for-the-treatment-of-adult-patients-with-relapsed-or-refractory-large-bcell-lymphoma-after-two-or-more-lines-of-systemic-therapy
- Tufts Center for the Study of Drug Development, 2016. Promise of Immuno-Oncology Therapies is Boosting R&D Funding, Alliances; http://csdd.tufts.edu/files/uploads/Summary-MarAprIR2016.pdf