Four Republican lawmakers have authored new legislation to permit drugs for critically ill patients to enter the market before completing late-stage trials, saying the bill was necessary because the U.S. Food and Drug Administration's regulatory process was too slow and burdensome.
The bill would create a time-limited conditional approval pathway in the U.S. similar to a system that has long been used by European regulators.
But the bioethicist community immediately raised concerns that patients could be exploited under the legislation, particularly when it comes to paying for the treatments because U.S. insurers are unlikely to cover the costs of the medicines when questions about safety and efficacy are not fully known.
"As I read it, manufacturers could charge whatever they want for the drugs," said Jeremy Snyder, a professor and bioethicist at Simon Fraser University.
There is nothing in the bill that would require insurers to cover products with conditional approval.
Rep. Bruce Westerman
The House bill is sponsored by Republican Reps. Bruce Westerman of Arkansas, Mike Gallagher of Wisconsin and Tim Burchett of Tennessee. Sen. Mike Braun, R-Ind., authored the Senate legislation.
The conditional approval would be valid for one year and could be renewed annually for up to five years. The pathway is intended for new products to treat, prevent or medically diagnose seriously debilitating or life-threatening diseases or chronic conditions that lack meaningful treatments.
The therapy's expected benefits must also outweigh its potential risks. Companies would be required to meet certain obligations, like completing clinical investigations to provide full demonstration of safety and effectiveness and other studies.
Manufacturers would also have to demonstrate that necessary postmarket surveillance and risk management tools were in place.
The products would be required to state in their labeling and promotional materials that they are conditionally approved by the FDA pending a full demonstration of effectiveness.
Companies could seek full U.S. approval at any time. The FDA would be required to let manufacturers include in their applications the real-world evidence they collected during the conditional approval period.
Even though the FDA has had an accelerated approval process in place since 1992, the four Republicans said that regulatory pathway is not sufficient to speed promising therapies to patients with life-threatening and debilitating diseases that lack effective treatments and cures, such as amyotrophic lateral sclerosis.
"Sometimes these medicines are backlogged in a bureaucratic, expensive FDA process that delays them from coming to market faster," Burchett said in a Dec. 19 statement.
"Patients with fatal diseases are fighting for their lives every day while real, meaningful, life-extending treatments sit on the shelf just beyond their reach," Braun added.
The lawmakers want the FDA to be able to grant the limited marketing authorization to new drugs that have successfully completed phase 1 and 2 trials, with the idea that companies could generate revenue to help fund their phase 3 studies.
They emphasized their legislation is targeted especially at small biopharmaceutical companies that may struggle to cover the costs of late-stage trials.
While the lawmakers said some phase 3 trials cost "billions of dollars" to complete, researchers at Johns Hopkins University reported in a September 2018 analysis that the median cost for studies to support FDA approvals of new drugs was $19 million.
Sen. Mike Braun
Braun first revealed he was drafting his legislative proposal at the Nov. 20 Senate confirmation hearing for Stephen Hahn, who was sworn in as FDA commissioner on Dec. 17.
At the hearing, Hahn told Braun that while it is important to expedite new innovations to patients, he would "want to make sure that these approaches are validated, so that we don't make huge mistakes that hurt patients."
Making products available under a conditional approval may result in some companies having difficulty enrolling patients in well-controlled phase 3 trials, Holly Fernandez Lynch, assistant professor of medical ethics at the University of Pennsylvania, told S&P Global Market Intelligence.
"Instead of trying to short circuit the FDA process, we have to be serious about the fact that most products fail," she said. "Why are we rushing to get them to market?"
About half of investigational drugs entering late-stage clinical development fail during or after pivotal clinical trials, primarily because of concerns about safety, efficacy or both. Most of those failures — 57% — were due to inadequate efficacy, Fernandez Lynch said, citing a December 2016 analysis in JAMA Internal Medicine.
The conditional approval bill also includes a provision protecting manufacturers from liability.
"It's like an acknowledgment that many of these products really will not be safe and effective in a way that could hold up to basic tort standards of reasonableness," Fernandez Lynch said.
She also took issue with the lawmakers' claims that FDA was sitting on a stockpile of safe and effective medicines.
"FDA is not some cartoon villain," she said. "Patients battling terrible diseases don't want just anything, they want medicines that work. FDA gatekeeping helps make that a reality."
A patient's perspective
But Corey Polen, who has ALS, said the bill would provide another option for manufacturers to supply patients with terminal diseases access to promises treatments.
He said current pathways to early-stage therapies, including the FDA's compassionate use program and the Right to Try Act — a law that lets Americans sidestep the U.S. regulatory agency to obtain unapproved experimental treatments — have provided "extremely rare access" to patients with ALS, "even though there are very promising treatments in every phase of the clinical trial process."
"This conditional approval pathway provides the FDA authority to regulate such access for the patients of the diseases that need it the most," Polen told S&P Global Market Intelligence.
"The harsh reality is that ALS patients are on an expedited timeframe and access has never worked," he said." We must find better options, sooner rather than later."
Rep. Jeff Fortenberry, R-Neb., also introduced a bill in the House on Dec. 18 that seeks to ensure all patients with ALS in the treatment and placebo arms of clinical trials are provided access to the drug being tested and that all studies going forward require treatment arms for all participants.
The legislation came just as the FDA issued new draft guidelines in which the agency outlined circumstances where not using a placebo control may be acceptable.
The agency also highlighted the circumstances in which using a single well-controlled trial would be appropriate.
In addition, the FDA said makers of drugs intended for rare diseases should consider designing their phase 1 first-in-human study to be an "adequate and well-controlled clinical investigation that has the potential, depending on the trial results, to provide part of the substantial evidence of effectiveness to support a marketing application."