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Annual side effects reporting under US FDA Right to Try proposal raises concerns

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Annual side effects reporting under US FDA Right to Try proposal raises concerns

SNL ImageThe U.S. Food and Drug Administration proposed allowing drugmakers to report only once per year the side effects they become aware of related to their experimental products used by critically ill patients under the Right to Try Act.

Once the FDA's proposed rule is finalized, companies must start no later than March 31 of each year to submit an annual summary of the medicines they have provided to patients under Right to Try, or RTT.

The summary must include the number of doses supplied of an eligible experimental drug, the number of patients treated, the use for which the medicine was made available and any known serious adverse events, or SAEs, the FDA said in a document posted online July 23 in the U.S. Federal Register.

RTT allows patients with life-threatening diseases or conditions to sidestep the FDA's expanded access program, also called compassionate use, to seek treatment with unapproved medicines outside the clinical trial process.

The law does not force biopharmaceutical companies to provide their experimental treatments to U.S. patients. The ultimate decision for access is left in the hands of those manufacturers.

Even though RTT was enacted in May 2018, the FDA has been slow to get the mandate's reporting regulations in place, so drugmakers have not yet had to provide the information to the agency.

It is not known how many RTT requests have been made or the number of patients who have been treated under the program.

The first U.S. patient known to have received an investigational therapy under RTT died of recurrent glioblastoma in 2019, the company that provided that treatment, Epitopoietic Research Corp., reported to S&P Global Market Intelligence. ERC has also let other patients use the drug, Gliovac, under RTT.

Brainstorm Cell Therapeutics Inc. has permitted a single patient, Matt Bellina, to use its experimental amyotrophic lateral sclerosis therapy NurOwn under RTT.

Critics of RTT have said the law was devised to weaken the FDA's regulatory authority and could result in the marketing of unproven and potentially dangerous products to desperately ill patients.

Some companies have recently been formed with the intent of monetizing the law.

When President Donald Trump signed RTT, he said it would save "countless" lives, potentially "hundreds of thousands."

SNL Image
Holly Fernandez Lynch, assistant professor of medical ethics at the University of Pennsylvania
Source: University of Pennsylvania

With the FDA's rule not expected to be finalized until after the U.S. November elections, Americans will not have the information to weigh Trump's claims before then, said Jeremy Snyder, a professor and bioethicist at Simon Fraser University in Canada.

In its proposed rule, the FDA estimated that only as many as six drugmakers would prepare and submit annual summaries, noted Holly Fernandez Lynch, assistant professor of medical ethics at the University of Pennsylvania.

Adverse events

Fernandez Lynch and others in the bioethicist community raised concerns about drug companies not being required to report SAEs of their experimental medicines until doing so in their annual Right to Try summary reports. This means it could be as long as 15 months after the side effect occurred before the FDA was informed.

"What if there is an RTT SAE that would actually be really critical for clinical trial investigators to be aware of to protect their participants? They might not learn of it till far too late," Fernandez Lynch told S&P Global Market Intelligence.

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Patti Zettler, associate professor at The Ohio State University Moritz College of Law
Source: The Ohio State University

The FDA's existing clinical trials regulations require reporting SAEs within 15 calendar days, which is much more rapid, she said.

But there is no reason why companies could not voluntarily report SAEs to the FDA, said Patti Zettler, associate professor at The Ohio State University Moritz College of Law.

"I think it would be helpful to the agency to make that clear and encourage such voluntary reporting," Zettler told S&P Global Market Intelligence.

Still, the U.S. regulator is not requiring certifying physicians to report RTT safety data to the drugmakers, Fernandez Lynch said.

So unless manufacturers voluntarily require doctors to give them that information, "which they absolutely should, it's possible they might not become aware of it," she said. "I think that is a big problem."

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Leigh Turner, associate professor at the University of Minnesota Center for Bioethics
Source: Office of Leigh Turner

Enforcement

There is also no enforcement mechanism in the law or the FDA's proposed rule for reporting the SAEs, said Lisa Kearns, senior researcher in medical ethics at NYU Grossman School of Medicine.

"We are relying on manufacturers to be compliant, but we know that there is nowhere near 100% compliance with the 21st Century Cures Act's requirements to post information about [expanded access] policies on manufacturer websites," Kearns said. "Whence, the optimism that things will be better with RTT reporting?"

The FDA said because of disclosure laws, it could not answer patients' questions about whether a product is eligible for RTT and said companies would be in the best position to respond — which is also concerning, said Leigh Turner, associate professor at the University of Minnesota Center for Bioethics.

"So companies could make misleading representations that are not addressed by the FDA before investigational products are administered to patients on an RTT basis," Turner told S&P Global Market Intelligence. "Some companies might be happy to exploit the FDA's unwillingness to address whether particular products are eligible."

There is also the question of whether anyone is going to pay attention to the fees some patients will be charged to access products under RTT, he added.