It seems that every week a major breakthrough in the understanding of cancer is announced in the media. So where are all the drugs that should flow from these discoveries?
Unfortunately, the road from laboratory research to government approval is long, lasting upwards of 15 years and costing in excess of A$5 billion per drug.
The increasingly long approval time and high cost are inevitable and a reflection of the high standards being applied to medicines by government regulators such as the Therapeutic Goods Administration (TGA) in Australia and the US Food and Drug Administration.
The commercialisation process
Often, when a researcher’s work is announced to the public, surprisingly few developmental experiments have been completed. At the stage where a new discovery is announced by a university-based researcher, it’s probable that only a few test tube-like tests have been completed, backed by simple animal studies.
Armed with these basic results, the researcher will try to partner with a pharmaceutical company to develop the drug. The high cost of developing drugs means that these companies are usually large transnational corporations such as GlaxoSmithKline, AstraZeneca and Pfizer, to name just a few.
Alternatively, the researcher may start her own company, bank-rolled by business angels or through venture capital organised by her university.
Just getting a company interested in a new drug, or starting a spin-out company, can take one to two years.
Drug testing and approval
Before a new drug can be tested in humans, it must undergo comprehensive preclinical screening and testing.
This process tests for the full spectrum of side effects, the best formulation of the drug (oral tablet versus injection, for example), the drug’s stability, and which cancers the drug is best used to treat. In total, these tests can take upwards of four years.
Once a pharmaceutical company has compiled all this data, it can then seek approval for Investigational (New) Drug status from the TGA and plan for human testing.
Human clinical trials are divided into three phases that seek to specifically determine if the drug is safe, if it works, and whether it is better than currently prescribed drugs.
For most other types of drugs, a placebo is used in human trials so as to discount any positive results that arise simply because the patient thinks the drug will work. Placebos can be sugar tablets or saline injections with no active drug included at all.
But placebos are rarely used during the clinical trial process for cancer drugs. This is because cancer may be fatal and to give a placebo to a dying patient, who therefore has no chance of cure, would be unethical. A placebo is only used where there’s no existing treatment against which the new drug can be compared.
Clinical trials are the longest and most costly part of the drug approval process. It’s common practice to run decade-long trials, involving many thousands of patients, dozens of doctors, spread over multiple hospitals and even across different countries.
Government approval
Once all the clinical trial data has been collated, the company then applies for marketing approval through what is commonly called a New Drug Application.
This approval process precedes and is different to listing a drug on the Pharmaceutical Benefits Scheme, which aims to make drugs more affordable.
While anti-cancer drugs generally go though testing and approval faster than other classes of drugs, the past decade has seen the process begin to lengthen significantly.
As cancer treatment moves into the era of personalised medicine, the number of people eligible for clinical trials has become smaller. So it takes longer to recruit enough patients to get reliable data.
Coupled with the lengthening drug development pipeline, human trials also have unenviable failure rates. The failure rate of drugs in cancer clinical trials between 1993 and 2004 was found in one study to be as high as 86%. This number gets even higher if drugs that fail during preclinical testing are included.
That failure rate is getting higher as the TGA and its sister agencies around the world place tighter controls on the safety and efficacy of the drugs they are willing to approve.
What we need now is improved testing methodologies to predict which drugs are more likely to pass human trials.
Better screening at the commercialisation and pre-clinical stages can save years of development time and millions of dollars for companies and governments.
There are a number of ways we can do this, including the development of better animal models that more closely resemble cancers in humans or the development of genetic screening tests to determine which patients are most likely to gain a benefit from the new drugs.
More importantly, better preclinical screening means fewer patients involved in the burden of clinical trials, cheaper drugs that are more affordable to both patients and government health systems, and safer drugs with fewer side effects and better effectiveness.