Pharmaceutical companies, with broad support from the US government, formulated vaccines against SARS-CoV-2 in record time. Masking and social distancing could only get us so far. The vaccines arrived about a year after the virus began ricocheting around the world and triggering lockdowns, an economic crisis and the biggest public health emergency since the 1918 Spanish flu.
There has been success in a field where many of the biggest medical problems, including the SARS CoV-1 virus that struck in 2002, have no cure or effective remedy. The truth is that drug development failure rates are extraordinarily high. Despite countless billions of public and private dollars invested in their fight, the drug failure rate is 97% for cancer and 99% for Alzheimer’s disease. There is no cure in sight for these scourges.
And then there are the drugs used for medical treatments that have unforeseen effects. Adverse drug reactions, taken as prescribed, are the 4th leading cause of death in the United States, causing 1.9 million hospitalizations annually, and 128,000 of these personal crises are fatal.
The average time to market for a new drug, with the risks and often the rewards limited, is 10 to 15 years – a stark contrast to the year-long sprint drug developers achieved on the SARS vaccine CoV-2.
One of the main reasons for the slowness of dangerous and often ineffective and even dangerous treatments in our current drug development paradigm: an archaic federal law, the Federal Food, Drug and Cosmetic Act (FFDCA) of 1938, requires Drug sponsors have to submit tons of animal testing data before using experimental drugs in human trials.
Data show that animal testing is poor predictor of human response to drugs. Between 90 and 95 percent of drugs found to be safe in non-clinical testing fail in human clinical trials due to toxicities not predicted by traditional animal testing or because they simply don’t work in their human subjects. .
The price of a new drug is estimated on average between 1 and 6 billion dollars. The costs borne by drug developers are then absorbed by consumers. And drugmakers often don’t want to invest in drugs whose market potential is lower than their research and development costs.
The FDA Modernization Act, S. 2952/HR 2565 — led by Kentucky Sen. Rand Paul, R-Bowling Green, and Sen. Cory Booker, DN.J., and HR 2565, introduced by Rep. Vern Buchanan, R-Fla. , and Elaine Luria, D-Va. – has the potential to streamline drug development, drive innovation and reduce unnecessary burden on animals. The legislation removes the mandate for animal testing and allows for the best investigative strategies, whether animal or non-animal methods.
Human-relevant cellular assays, organs-on-a-chip, humans-on-a-chip (microphysiological systems), and computer modeling have been developed to more accurately predict human response to new drugs, but the FFDCA has not officially recognize these superior test methods. FFDCA and FDA regulations specifically mandate the use of animals, excluding non-clinical methods based on human biology. These groundbreaking discoveries can do nothing if they don’t leave the lab.
Last month, Quris announced that a candidate therapy for fragile X syndrome had been developed using a bio-artificial intelligence clinical prediction platform and is expected to enter clinical trials in 2022. The company uses artificial intelligence (AI) combined with a “patients-on-a-chip” to predict the safety and efficacy of therapeutic candidates before they are used in human trials.” We are at the tipping point of modernizing drug discovery,” according to Moderna co-founder Robert S. Langer.
Recently, the FDA’s Advisory Committee on Cell, Tissue, and Gene Therapies concluded that animal models are “problematic” for assessing the safety risks of gene therapies derived from adeno-associated virus (AAV) vectors. There have been “serious” adverse events in clinical trials of AAV vectors, including cases of acute liver and kidney failure in children. A third of the 500 children under two years of age treated with Zolgensma had at least one adverse event of hepatotoxicity.
We are entering the era of personalized and precision medicine in healthcare, and this trend further exposes the flaws in our existing regulatory framework. Again, animal models will be of little value because other species can hardly be expected to capture biological variation in humans. Non-clinical tests or studies using human cells and tissues, however, may reveal biological variations within the human population. They have the potential to serve as “clinical laboratory trials” and test the safety and effectiveness of a drug for individual patients.
It’s time to change the FFDCA to give drug sponsors more options to test drugs for safety and efficacy to improve clinical trial attrition rates, cut time to market in half, the market and considerably reduce research and development costs which could reduce drug prices by five.
Wayne Pacelle is president of Animal Wellness Action. Tamara Drake is director of research and regulatory affairs for the Center for a Humane Economy.