Author: Noah Noonan, BS
Clinical Perspective: John D. Powderly MD, CPI
Advancements During a Pandemic
The COVID-19 pandemic has radically interrupted the American healthcare landscape in a manner unseen since the 2009 H1N1 Influenza Pandemic (CDC). Now more than ever, healthcare, pharmaceuticals, and biotechnology are in the public spotlight as the world tenuously awaits a vaccine. This is an opportune moment to reflect on how these fields have collectively advanced the treatment of cancer, prolonged the life of cancer patients, and improved the quality of life for those afflicted. Cancer patients must now confront a new challenge: fighting their disease during a public health crisis. Fortunately, groundbreaking cancer research has continued even in the face of global supply chain breakdowns and disruptions to the workforce, and the field of Immuno-Oncology continues to advance.
Cancer Immunotherapy, or Immuno-oncology, involves the use of checkpoint inhibitors, cellular therapy, cancer vaccines, and other modalities to treat cancer. Immuno-oncology is now an established and effective treatment option for both solid and hematological malignancies. The field can be traced back over 100 years ago to anecdotal reports of systemic anti-tumor response after irradiation of only a single tumor lesion or administration of Coley Toxins – intentional injections of infectious bacteria designed to stimulate the immune system. Additionally, many drugs developed through the late 20th century are immunotherapeutics, even if the mechanisms of action were unknown at the time. While Immuno-oncology encompasses many drug classes, the main drivers for this field have been checkpoint inhibitors and cellular therapies .
The first wave of immuno-oncology trial approvals arrived in the early 2010’s and proceeded to undergo massive growth. From 2014 to 2017, new trials in immuno-oncology soared from 250 to almost 600, reaching double digit growth rates each year as drug classes diversified. This rapid growth was mostly driven by biomarker and checkpoint inhibitor studies. Biomarker studies seek to correlate measurements of substances in the body to the occurrence and outcome of a disease or health event. Checkpoint inhibitor studies are designed to target regulating mechanisms within the immune system that can either increase or decrease the bodies response to infection, insult, and injury. In 2011, checkpoint inhibitor ipilimumab received a seminal U.S. Food and Drug Administration (FDA) approval for the treatment of melanoma. Ipilimumab targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), a protein that down regulates the immune response, and became the first checkpoint inhibitor to be approved by the FDA. Dr. James P. Allison shared the Nobel Prize in Physiology or Medicine in 2018 for his discovery of the CLTA-4 pathway and its involvement in cancer immunotherapy. In 2014 the first programmed cell death protein 1 (PD-1) inhibitor, nivolumab, was approved by the FDA. The PD-1/PD-L1 pathway has since become a staple in field of Immuno-oncology due to its strong modulation of the T cell response. John D. Powderly MD, CPI, founder and president of Carolina BioOncology Institute, was a Principal Investigator in the early phase 1 trials for CTLA-4, PD1, and PDL1 mAbs.
Contrary to the previous decade of growth, there has been a notable plateau in the number of Immuno-Oncology approvals into 2019 . This indicates both a maturation of the market and the patient population which these therapeutics target. The evidence for a maturing market is corroborated by a statistical analysis performed with a literature mining approach. This literature mining analysis was generated from a pool of over 93,000 publications in the field of Immuno-Oncology and showed a clear transition from early phase clinical trials to randomized control trials in 2019-2020. The analysis also noted that the most prevalent cancer types included in these studies were breast, lung, and colorectal and observed a shift in focus from hematological to solid tumors .
While the Immuno-Oncology market may be maturing in certain drug classes, cell therapies are growing rapidly and outpacing all other immunotherapeutics. Globally, the cancer cell therapy pipeline included 1,483 active agents in March 2020 — an increase of 472 agents from March 2019. Chimeric antigen receptor T (CAR-T) cell products saw the greatest growth during this time (77% increase from 2019 to 2020) . A recent article published by Upadhaya et al. in Nature Reviews Drug Discovery (202) illustrates how in just five months, as of August 14, 2020, the number of cancer cell therapy agents has increased by 7.7% to 1,597 (figure above left) . This increase in cell therapy agents under study is also shaping the physical Immuno-Oncology landscape in regional distribution of development. The initial wave of checkpoint inhibitor studies came mostly from the US and into Europe. Now, alongside the United States and Europe, China is also a large contributor to cell therapy investigational products .