Sen. Rand Paul’s FDA Modernization Act could transform medical treatment

Pharmaceutical companies, with ample support from the U.S. government, formulated SARS-CoV-2 vaccines in record time. Masking and social distancing could only take us so far. The vaccines came about a year after the virus starting ricocheting around the world and triggering lockdowns, an economic crisis, and the biggest public-health emergency since the Spanish flu of 1918.

There was success in a field where many of the biggest medical problems, including the SARS CoV-1 virus that struck in 2002, have no cures or effective remedies. The truth is, drug development failure rates are extraordinarily high. Despite countless billions of public and private dollars invested in fighting them, the drug failure rate is 97% for cancer and 99% for Alzheimer’s. There are no cures in sight for these scourges.

And then there are the drugs used for medical treatments that have unpredicted effects. Adverse reactions to drugs, taken as prescribed, are the 4th leading cause of death in the United States, causing 1.9 million hospitalizations per year, and 128,000 of these personal crises are fatal.

The average time to market for a new drug, with the risks and often the limited rewards, is 10 to 15 years – a sharp contrast to the one-year sprint drug developers made on the SARS CoV-2 vaccine.

A primary reason for the slow pace of unsafe and often ineffective and even dangerous treatments in our existing drug development paradigm: an archaic federal statute, the Federal Food Drug and Cosmetics Act (FFDCA) of 1938, mandates that drug sponsors submit reams of animal testing data before investigational drugs are used in human trials.

The data show that animal tests are miserable predictors of the human response to drugs. Between 90 and 95% of drugs found safe in nonclinical tests fail during human clinical trials due to toxicities not predicted by traditional animal tests or because they simply don’t work in their human subjects.

The price tag for a new drug is an estimated average of $1 billion to $6 billion. Costs borne by drug developers are later absorbed by consumers. And drug manufacturers often don’t want to invest in drugs that have a commercial potential less than their research and development costs.

The FDA Modernization Act, S. 2952/H.R. 2565 —led by Kentucky Senator Rand Paul, R-Bowling Green, along with Senator Cory Booker, D-N.J., and H.R. 2565, introduced by Reps. Vern Buchanan, R-Fla., and Elaine Luria, D-Va. — has the potential to streamline drug development, spur innovation, and reduce the unnecessary toll on animals. The legislation wipes away the animal testing mandate, and allows the best investigational strategies, whether animals or non-animal methods.

Human-relevant cell-based assays, organs-on-a-chip, human-on-a-chip (microphysiological systems), and computer modeling have been developed to more accurately predict human response to new drugs, yet the FFDCA does not officially acknowledge these superior test methods. The FFDCA and FDA regulations specifically require the use of animals, to the exclusion of human biology-based nonclinical methods. These breakthrough discoveries can’t help if they don’t leave the lab.

Last month, Quris announced that a candidate therapy for fragile X syndrome was developed using bio-artificial intelligence clinical prediction platform and is set to enter clinical trials in 2022. The company uses artificial intelligence (AI) combined with a “patients-on-a-chip” platform to predict the safety and effectiveness of therapeutic candidates before they are used in human trials. “We are at the tipping point of the modernization of drug discovery,” according to the co-founder of Moderna, Robert S. Langer.

Recently, FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee concluded that animal models are “problematic” in assessing the safety risks of gene therapies derived from adeno-associated virus (AAV) vectors. There have been “severe” adverse events in AAV vector clinical trials, including instances of acute liver and kidney failure in children. One third of the 500 children under the age of two treated with Zolgensma had at least once adverse event of hepatoxicity.

We are entering the era of personalized and precision medicine in health care, and that trend further exposes the defects of our existing regulatory framework. Here again, animal models will have little value since other species can hardly be expected to capture biological variation among humans. Nonclinical tests or studies using human cells and tissues can, however, portray biological variation among the human population. They have the potential to serve as “clinical trials in a lab” and to test a drug’s safety and effectiveness for individual patients.

It’s time to tweak the FFDCA to provide drug sponsors more options for testing the safety and efficacy of drugs to improve clinical trial attrition rates, cut time to market in half, and substantially reduce research and development costs that could cut drug prices fivefold.

Wayne Pacelle is president of Animal Wellness Action. Tamara Drake is director of research and regulatory affairs for the Center for a Humane Economy.