In his 2016 State of the Union address, President Barack Obama announced the National Cancer Moonshot Initiative, a $1 billion government-wide strategy to detect, cure, and eliminate all kinds of cancer. This ambitious announcement is representative of the advancements that have been made in the field of biomedicine; it highlights how massive investments in the sciences have helped to bring effective treatments for terminal illnesses for millions of people.
Personalized precision drug treatment, which uses molecular biomarkers in genomic sequences to fight life-threatening illness, is one of the most important of these new initiatives. Unfortunately, however, it faces headwinds in terms of high costs and incompatible regulations. These obstacles include the outdated FDA approval process, overly expensive clinical trials, and incompatible surrogate requirements for biomarker drug accelerated approval.
First, the outdated FDA approval process has restricted the ability of personalized precision medicines to reach the patients that need them the most. Despite rapid innovation in gene sequencing – the first time a human genome was sequenced in 2003, it cost $3 billion dollars and took over 13 years, whereas today, a $1,000 sequencing machine can sequence an entire genome in a few hours – the FDA’s current one-size fits all drug approval process requires a new drug to benefit 48 out of 50 patients in a trial, or it will deny approval. This rigid approval process misses the point of precision medicine: personalized treatment to each individual based on his or her own genetic code. By not considering the relevant details of patients’ side-chemistry, and not allowing more flexibility in the drug approval process, medical treatments are not as effective or safe as they could possibly be. The crowd science-based medicine approval process, which uses randomized, double blind, placebo-controlled clinical trials only looks for statistically robust one-dimensional correlations with a desired change in clinical trial conditions. In contrast, precision medicine requires matching a medication to a specific type of patient. Thus, the current clinical trial approval process will not effectively demonstrate the benefits of precision medications. Life-saving drugs, such as the tumor shrinking medication, Iressa, have been made unavailable due to the current standard operating procedures of the FDA.
Secondly, the FDA’s current approval process has increased costs to develop new-targeted drugs and will discourage future investment and research. Of the three-phase drug approval process, Phase III clinical trials typically take 3 years and are 90% or more of that drug’s development costs. Pre-market medical research has brought the total cost of bringing a drug to market to $1.3 billion dollars. Total cost is expected to continue rising as drug trials become increasingly expensive and unnecessarily rigorous. Even with tax breaks and market exclusivity, stakeholders in Alzheimer’s drugs, diabetes drugs, and “orphan drugs” (drugs intended for diseases suffered by 200,000 Americans or less), are wary of entering the market due to the high failure rate and the expenses of taking these therapies to clinical trials.
Lastly, while the FDA’s current accelerated approval process provides the regulatory framework in which the FDA can allow drugs that use molecular biomarkers to be accelerated through the drug evaluation and approval process, this framework is flawed and is mostly used only for serious and life threatening illnesses. This accelerated approval process hinges on surrogate endpoints that the FDA deems to be “reasonably likely” to predict clinical outcomes and address serious conditions which the FDA has historically considered immediately life-threatening illnesses.
Limiting the accelerated approval process to life threatening diseases alone is not responsive to the health issues that many Americans face today. The greatest dangers to long-term public health are chronic non-communicable diseases such as heart ailments, diabetes, stroke, and cancer. Since the 1993 enactment of this process, only 9.6% of new molecular entities have been granted accelerated approval. The U.K. is preparing to revamp their drug approval protocols to incorporate biomarker science during their drug approval process. These global competitors hope to shift pharmaceutical R&D, money, and jobs from the U.S. to foreign shores.
The issue is clear: for continued growth in U.S. precision biomedicine and strengthened competitiveness abroad, the U.S. must take measures to ensure expedient and inexpensive drug approval for pharmaceutical manufactures. In particular, the U.S. must ease the regulatory burden of the FDA by allowing for a more flexible and cost-effective testing process and create surrogate requirements conducive to biomarker drug accelerated approval by collaborating with the National Institute of Health (NIH) and the Institute of Medicine (IOM), which have existing expertise in defining these regulations. With non-communicable diseases being responsible for the majority of American deaths, it is urgent that the U.S. government and the FDA create a more favorable climate to develop precision medicine to fight these ailments.
