Bipartisanship prevailed on a health issue Wednesday, as the Senate teed up a revised version of Sen. Ron Johnson’s “right-to-try” bill in a move that both clears the way for a quick reauthorization of an FDA funding package and blocks the agency from interfering with terminally ill patients seeking access to experimental medicines.
The Senate is expected to take separate votes Thursday on an FDA user fee reauthorization and Johnson’s bill. Johnson had earlier threatened to hold up the FDA bill if it didn’t contain right-to-try.
The updated version is the product of a bipartisan deal between leadership of the Senate HELP Committee and Johnson, who came up with a proposal that addressed concerns of FDA and public health advocates while still limiting the federal government’s role in personal medicine decisions. The right-to-try issue has gained prominence in recent months, fueled in by laws passed in more than 30 states and the backing of Vice President Mike Pence,
FDA and public health officials worried Johnson’s initial draft could endanger and bankrupt patients while undermining the authority of the FDA and the process for ensuring medications work.
Public health advocates, industry and legal experts remain lukewarm about the update, which would let patients and their doctors nationwide circumvent FDA’s oversight of experimental medicines.
The bill looks to be an “improvement,” said Patti Zettler, a professor at the University of Georgia and former associate chief counsel at FDA, noting that the compromise addresses concerns that safety information on experimental drugs is reported to FDA and that patients cannot be charged excessive amounts for right-to-try drugs.
“However, the fundamental problem with the bill is not resolved in that it still envisions removing, or drastically reducing, FDA’s role in expanded access,” said Zettler, referring to FDA’s program for granting patients access to experimental drugs outside of clinical trials.
The Trickett Wendler, Frank Mongiello and Jordan McLinn Right to Try Act of 2017 (S. 204 (115)) would authorize the use of unapproved medicines by patients diagnosed with a life-threatening illness as long as the drugs in question have already been tested in the first phase of human clinical trials and are continuing on in further FDA-overseen research. Patients must have exhausted other treatment options and be unable to participate in ongoing clinical trials.
Drug companies wouldn’t be required to give patients medicine under the law, but it would remove the hurdle of companies and physicians needing FDA’s sign off to treat patients with experimental medicines.
The updated bill requires that drug companies submit yearly reports on drugs provided under right-to-try, including documentation of adverse events. It’s intended to ensure oversight and prevent multiple patients from experiencing the same harm from a medicine, said advocates, who still worry that yearly reports may not be frequent enough.
“It does leave a window where this is a high potential for unknown,” said Jeff Allen, president and CEO of Friends of Cancer Research, which has argued that FDA should remain involved in decisions around experimental medicines. Patients, Allen said, need “the maximum amount of information so they can make an informed choice.”
Another tweak in the bill gives FDA some ability to use adverse event information from righ- to-try cases when approving a drug or making decisions about whether its clinical trials can continue. This change was also met with mixed reaction.
“This may mitigate some concerns about tying FDA’s hands with respect to what information it can consider, although it is not a blank check for FDA to consider any and all clinical outcomes [from right to try],” Zettler said.
The revised bill keeps a controversial provision that would allow access to right-to-try after drugs pass through Phase I clinical trials.
Right-to-try advocates say that means a drug has been deemed “safe.” But Phase I studies involve small populations, as little as a handful of patients. They are generally designed to find an appropriate dose of the drug, not to demonstrate safety or efficacy. They may not even test a drug in sick patients — and they aren’t necessarily testing the drug for the same disease patients are requesting it in a right-to-try situation.
For every 100 drugs that are tested in Phase I trials, FDA estimates that only about five to seven will ultimately get approval — meaning that the drug’s benefits are believed to outweigh its risk and can be marketed on a wide scale to U.S. patients.
“Its hard to set an arbitrary point in time that makes sense for most products,” to be deemed suitable for compassionate use situations, Allen said. It needs to be a case-by-case decision by doctors, FDA and experts at the drug company.
The updated bill also “doesn’t solve the root problem” of getting drug companies to provide experimental drugs for patients outside of their formal clinical trials, Allen added.
Many skeptics point out that FDA already approves about 99 percent of “compassionate use” requests that make it to the agency’s door. If there’s a stumbling block, they say it’s convincing a drug company to be willing to provide the drug.
Manufacturers have a number of concerns with providing patients drugs outside of their clinical trials, including that it detracts from the lengthy and expensive research they must conduct to get FDA approval so the drug can reach wide swaths of patients.
“This right-to-try proposal still has the potential to compromise clinical trial projects,” said Doug Peddicord, the executive director of ACRO, which represents contractors that conduct clinical trials for the drug industry.
ACRO argues that right-to-try could exacerbate the challenge of recruiting and retaining enough patients in clinical trials. For rare diseases, even a few patients opting for right-to-try over a clinical trial could severely delay or comprise the drug development effort, placing all patients who need that treatment at risk, ACRO says.
Another change to the Johnson bill could actually open up right-to-try to more patients, said Jeanie Kim of Yale Law School. That’s because the revised draft says patients with life-threatening illnesses, not just those with terminal diseases, can utilize the law.
The legal definition of life-threatening disease is much broader than what is considered a terminal illness Kim said. Terminal illnesses usually only entail diseases that will result in death in a short period of time, while life-threatening diseases can include conditions that will ultimately be fatal, but not for many years.
Kim did note while the revised bill still contains a lot of liability protection for drug companies and doctors who provide treatments under right-to-try, it adds new exceptions that will give patients some ability to file legal challenges if there is reckless or negligent conduct.