Record approvals of new cancer drugs – what is the role of genomics?

Post by Matt Wasmuth, a postgraduate student at the University of Edinburgh. This post is adapted from work conducted as part of the ‘Biobusiness’ course.

Image of prescription drugs, produced by J. Troha, source National Cancer Institute. Reproduced under a Creative Commons Attribution-Share Alike 4.0 International license. Available online at:

Over the last decade, the number of new cancer patients in the United States has grown from 1.5 million per year to a projected 1.9 million for 2020. This has also resulted in an increase in spending on cancer treatment. This trend is not just restricted to the US. Global spending on cancer treatment is expected to reach $200 Billion by 2022, constituting 14% of total medical expenditure. This spending has paralleled the unprecedented number of drugs being approved for the treatment of cancer. Here I discuss some key changes within the oncology drug market over the last 10 years and assess the extent to which genomics has altered the dynamics of drug discovery.

Approval rates of cancer drugs continue to rise with an increase from 13% to 17% of novel drugs treatments from 2015 to 2019. What has stimulated this rise? The story begins with Richard Nixon signing the National Cancer Act in 1971, which led to increased funding directed towards oncology through the National Institutes of Health. The research that followed led to the recognition that cancer is not just one disease, but a collection of many – sometimes rare – diseases stemming from one or more genetic mutations. Due to the much smaller markets for treatment, rare diseases attract less investment into the development of potential drug therapies. To ameliorate this, The Orphan Drug Designation Program (ODDP) within the Food and Drug Administration (FDA) was established in 1983. The program aims to advance the development of products that demonstrate promise for the treatment or diagnosis of rare diseases by providing incentives for sponsors. The National Organization for Rare Disorders (NORD), originally spearheaded by patient groups affected by more widely-known disorders such as Huntington’s disease and severe combined immunodeficiency (SCID), gave the necessary impetus for the Act to take shape. Whilst members of these advocacy groups benefitted hugely from the research and products that arose from this movement, so did companies and research groups who develop cancer treatments. With more than 200 kinds of cancer now recognised, most potential treatments for rare cancers (those affecting 1/200,000) are eligible for the program. This also explains why the largest category of these un-profitable ‘orphan’ approved drugs is oncology. As of 2019, 21 out of 44 products approved were orphan drugs.

Figures on R&D spending in the pharmaceutical industry overall have not generally been matched by an equivalent rise in the rate of approvals, especially within Europe. Approvals within the oncology market buck the trend. This may be for a variety of reasons. One is that, as the genetic basis for various cancers become known, treatments have become more targeted. Indeed, they are now often approved with a companion diagnostic test that detects the genetic basis of the cancer.

Clinical trials are then optimised and designed for trial populations in which the genetics of the cancer has been characterised. Smaller patient numbers for rare diseases pose a challenge for clinical trial recruitment and for ensuring that the trials are statistically valid. However, novel clinical trial designs are being explored. For instance, predictive probability is employed to select patients most likely to benefit from treatment, based on their biomarker signatures. In cancer where time is a crucial factor, rather than using clinical end-points (remission rates), adaptive trial designs employ surrogate end-points (such as evidence of tumour shrinkage) or the detection of biomarkers such as HER2 gene overexpression, which is a feature in breast cancer, which exploit the relationship between the severity of the disease and response to treatment. These types of designs often allow for trials to be smaller and for decisions to be made faster.

A collaboration between the European Medicines Agency and the FDA launched in 2009. The product, a standardised application form concerning drugs wishing to enter both markets, yielded reduced approval times and as this approach becomes more refined will continue to do so. The UK government is aiming for regulation to take a more “streamlined, internationally competitive approach” in areas such as clinical trials resulting in further improved approval rates as well as encouraging the use of techniques such as genome editing by CRISPR-Cas9. Genome editing may make it possible to accurately modify the genome to provide a better understanding of cancer biology, highlight potential druggable targets and present a method of synthesising the drugs for these targets in cell factories.

Figure 1: Number of drugs new drugs approved from 1993-2019. Adapted from Mullard, 2020.

Significant developments in the treatment of cancer are not new. Radiotherapy was introduced in the 1900s, and chemotherapy in the 1940s. The next jump with targeted treatments such as monoclonal antibodies and Tyrosine Kinase Inhibitors in the 1980s was a more profound change, shaping the policy and regulatory landscape. Research efforts towards studying the genetics of cancer that began in the 1980s and the genomics of cancer from the 2000s are now bearing fruit, which is reflected in the spike we see in approvals for targeted treatments over the last three years (Figure 1). From the 1980s onwards, oncologists came to understand cancer as a molecular genetic disease by cataloguing different types of mutations found in tumours. These included mutations of the p53 gene, which implicated in cell cycle control and apoptosis, and therefore tumour suppression when active, and the development of tumours when inactivated. Genomic studies of the DNA sequences of particular tumours has enabled better-tailored treatments and also allowed the further stratification of cancer into the individual rare diseases that we know today.

However, the undoubted impact of genetics and genomics on diagnosis and treatment should not lead us to ignore the ongoing salience of monoclonal antibodies, immune proteins that can be designed to selectively attack cancer cells.

Due to the specificity of their targeting of cancer cells, in contrast with radiotherapeutic and chemotherapeutic approaches, monoclonal antibody therapy has taken off over the last decade and is expected to increase further not only as a cancer treatment but also in treating numerous other diseases (Table 1). Recently, antibody-drug conjugates that combine the specificity of an antibody with a cytotoxic (cell-killing) drug compound have been developed to target cancer cells. CAR-T cell therapy (Chimeric Antigen Receptor T cells) involves editing the genome of T cells, immune cells that kill other cells, to enable them to detect specific molecular markers (antigens) on the surface of cancer cells. This causes the T cells to attack those cells with high specificity (Mullard, 2020).

The limitations of particular immunological approaches such as monoclonal antibody therapy have not restricted its growth in all classes of drugs, including oncological. Methods such as genome editing are helping to further improve the specificity and effectiveness of immunological approaches. But genomics has also made its own distinctive contribution. It has enabled the stratification of cancer into multiple rare diseases that has been incentivised by the advantages of orphan drug designation. And it contributes towards the identification of new therapeutic targets, such as this one paper alone highlighting 5 novel gene targets from whole genome sequencing of over 500 patients.

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