Executive Summary

CBER director said unlicensed stem cell clinics often report adverse events not made public, which is a concern under Right To Try.

Asked about the US’s Right to Try law, Center for Biologics Evaluation and Research Director Peter Marks said he needed to “carefully side-step” the issue, but he was willing to discuss what he called a surrogate marker for the new framework.

During the Nov. 14 Biopharma Congress IV, sponsored by Prevision Policy and the Friends of Cancer Research, he was queried about the reporting adverse events for drugs administered through the controversial pathway. Marks did not offer a direct, or even a very politic answer, saying a proxy for right to try may be CBER’s policing of stem cell clinics providing treatments without a license.

“We know that we don’t get the appropriate reporting from those,” he said. “We don’t learn about things until something really bad happens.”

“I use that as my surrogate of what is possibly going to happen in this other area, but I don’t know for sure,” Marks added.

Right to try, enacted earlier this year, allows eligible patients with a life-threatening disease deal directly with drug companies to obtain an investigational treatment without FDA approval.

Sponsors providing drugs under right to try must report adverse events to the agency, but they cannot be used against the sponsor during the drug’s review unless necessary for a safety determination. (Also see “Right-To-Try Bill Heads To White House, Putting Firms In Driver’s Seat” – Pink Sheet, 22 May, 2018.)

The pathway will function separate and in parallel to the existing expanded access program, where FDA reviews and approves the petitions for use of investigational treatments. The Reagan-Udall Foundation hosted a meeting Nov. 19 on improving understanding of FDA’s expanded access program and using it to gather data for regulatory use. (See sidebar.)

An independent assessment of the expanded access program found public attitudes generally positive, but recommended the agency clarify how data from the program could be used for regulatory decisions and address manufacturer concerns about adverse events. (Also see ” Expanded Access: US FDA Told To Increase Regulatory Clarity, Early Interactions With Sponsors” – Pink Sheet, 8 Nov, 2018.)

Unreported Problems The Concern, Marks Says

During the conference, Marks, Center for Drug Evaluation and Research Director Janet Woodcock and Oncology Center of Excellence Director Richard Pazdur were asked whether they have been receiving right to try related adverse event reports.

Woodcock responded that a framework was being created, but “we’re kind of separate from that process.”

That prompted Marks to sidestep the question and relate right to try to problems with stem cell clinics.

Marks said often patients receiving unlicensed stem cell treatments fail to tell FDA about efficacy or safety issues.

“Because they’re invested in it, they don’t tend to report things or they tend to be told by providers ‘oh that’s kind of expected’ or this and that,” he said. “Some of them are actually embarrassed to report to the FDA because they realized after the fact that they got an FDA non-approved product.”

Marks said some of the problems reported to FDA are made public, such as patients receiving contaminated product and instances where “products get given to people that blind people” or “cause tumors in places they shouldn’t.”

But Marks added that many problems with unlicensed stem cell treatments are not disclosed, which he said makes right to try concerning.

“There’s a whole lot of things I can’t tell you about that get reported to us because they’re not in the public domain and that’s what really is scary in this area,” he said.

Marks has been more vocal about his concerns about right to try compared to other senior FDA officials. (Also see “Regenerative Medicines Provisions Of Cures Act A Top Priority For CBER” – Pink Sheet, 9 Jun, 2017.)

Opponents of right to try legislation argued that the pathway could be used to fleece patients into taking ineffective treatments and lower patient protections. (Also see “Right-To-Try Opponents Brace For Last Chance To Stop Bill” – Pink Sheet, 22 Mar, 2018.)

Is Anyone Using The Pathway?

So far there appears to be little manufacturer interest about right to try being made public.

Johnson & Johnson Chief Medical Officer Joanne Weldstreicher told the Reagan-Udall meeting that her company has not received any requests through right to try, and that company policy is not to “give access through that pathway” because it lacks the proper “checks and balances.”

While right to try was mentioned in passing by some panelists at the Reagan-Udall meeting, it was a topic FDA officials clearly did not want to discuss. When a member of the audience asked for comment on the law’s impact on expanded access, former FDA Commissioner Andrew von Eschenbach, the panel moderator, cut him off: “I’m sorry, but we aren’t going to discuss ‘right to try,” he said.

BrainStorm Cell Therapeutics Inc., which is developing the cell therapy NurOwn for amyotrophic lateral sclerosis, gained attention in June when it announced the company was open to providing the product to patients through right to try. But later that month the company said that after evaluating the legislation it would not make the product available through the pathway and focus on completing its Phase III trial.

The Goldwater Institute, a think tank that pushed state and federal right to try legislation, told the Pink Sheet that a physician helped nearly 200 patients receive Advanced Accelerator Applications SA’s Lutathera (lutetium Lu 177 dotatate) prior to approval through the Texas version of the law.

The product was approved for gastroenteropancreatic neuroendocrine tumors in January. FDA used data from an expanded access protocol in the Netherlands to support a broader indication than would have been possible using the data from the one pivotal trial. (Also see “Lutathera’s Broad Tumor Indication Aided By Expanded Access Data” – Pink Sheet, 18 May, 2018.)

The Goldwater Institute also said “we are now seeing growing interest and enthusiasm from manufacturers and the medical community” since President Trump signed the federal legislation.

FDA Commissioner Scott Gottlieb pledged to implement the legislation, but agency officials largely have refused to provide much help.

Woodcock has said that drug manufacturers must make their own decisions on how to handle right to try requests. (Also see “US FDA’s Woodcock: Sponsors Have To Make Right-To-Try Decisions” – Pink Sheet, 28 Jun, 2018.)

FDA’s website says it can answer some questions about right to try, but said patients should direct specific requests to their physicians. When the law was enacted, the agency directed staff to defer questions about the law to sponsors. (Also see “US FDA Right To Try Policy: For Now, Defer Questions To Sponsors, Bill Text” – Pink Sheet, 30 May, 2018.)

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