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‘Right to Try’ laws challenge clinical trial process

Wednesday, July 15, 2015

Should terminally ill patients be able to step around expanded access programs to gain access to investigational drugs simply because they believe, with the support of their doctor, that they will benefit?

Many state governments believe the answer should be yes.

Since early 2014, Right to Try laws have passed in 20 states, and currently, more are pending in 20 additional states.

The laws grant patients access to investi­gational drugs if they have a terminal illness, they’ve considered other options and their doc­tor will give them a prescription for it. Biophar­maceutical companies can choose to sell the drugs to patients or they can offer the drug for free. None of the new state laws specifies that the drug sponsors must offer the investigation­al treatment free of charge.

The laws purport to make the process faster and easier on patients than the FDA expanded access program. The Expanded Access to In­vestigational Drugs for Treatment Use program opens the gates for terminally ill patients to get experimental drugs if their doctor deems that they have no other treatment alternatives, if ac­cess to the drug will not interfere with clinical trial activity, the data thus far shows the drug to be safe and the drug sponsor is willing to give the patient the drug. These programs, often re­ferred to as “compassionate use,” require FDA approval as well as review and approval by an Institutional Review Board (IRB). About 1,000 people applied to receive experimental agents through this program from 2009 to 2013, and virtually all were told yes.

But critics of the FDA’s expanded access program say it’s too slow, that the paperwork is burdensome and the approvals process takes too long. Right to Try laws, they argue, will speed matters up for the dying who feel that their only hope lies in drugs that haven’t yet reached the market.

Others say the Right to Try movement is mostly a libertarian initiative started by the Goldwater Institute, a conservative organiza­tion whose leaders don’t like the regulatory power wielded by the FDA.

“The sickest Americans don’t have the lux­ury of time to wait for these drugs to come to market through the traditional process,” said Christina Corieri, healthcare policy analyst at the Goldwater Institute, in published reports. “The Right to Try Act puts the decision about whether to try an experimental treatment back where it belongs: in the hands of patients and their doctors.”

Currently, after an investigational drug has successfully completed phase I testing, it can take an additional six or more years for that drug to be approved for market even if clini­cal trials are demonstrating safety and efficacy. That’s not fast enough, say critics.

The Goldwater Institute came up with a draft for Right to Try legislation, and several states have used it. The state of Arizona used it almost verbatim in getting its laws passed.

The Pharmaceutical Research and Manu­facturers of America (PhRMA)—though it has not released an official statement on the move­ment—is not pleased about it, and would rather see patients gain access to investigational drugs under the oversight of the FDA and IRBs.

“We have serious concerns with any ap­proach to make investigational medicines available that seeks to bypass the oversight of the Food and Drug Administration and clini­cal trial process, which is not in the best inter­est of patients and public health,” said Sascha Haverfield, PhRMA’s vice president of scientific and regulatory affairs, in a statement.

“The clinical trial process is the primary mechanism by which patients may participate in the drug development process and receive access to unapproved investigational medi­cines,” he continued.

Those in research fear the movement—providing access to single patients when they ask—may result in slowdowns of the clinical trial process that brings drugs to market for thousands or more people. After all, if people can just request the drug, why participate in a clinical trial in which you might end up with placebo?

“Such programs pose real risks: conduct of an [expanded access program] may jeopardize enrollment or retention of patients in ongoing clinical trials of a drug that determine safety and efficacy and ultimately gain regulatory approval,” wrote Merck executives Michael Rosenblatt and Bruce Kuhlick in a viewpoint piece that appeared in the Journal of the Ameri­can Medical Association in May.

And if the patient using an experimental drug has a bad reaction, that can complicate a drug’s safety profile, even when the cause of the reaction isn’t clear, and this could further slow approval, they pointed out.

“Thus,” Rosenblatt and Kuhlick wrote, “in responding to patient’s understandable requests for compassionate access before ap­proval, companies need to consider not only their concerns but also society’s greater interest in development and availability of the drug for the larger group in need.”

Others in the industry are concerned that the program could become expensive for them, siphoning off the often very expensive com­pounds manufactured for trials, while remov­ing the opportunity for the drug maker to col­lect data.

Confluence of factors

The Right to Try movement got kicked up last year after the 2013 Academy Award-nom­inated movie “Dallas Buyers Club” drew atten­tion to the story of Ron Woodruff, a Texas man stricken with AIDS in the 1980s who smuggled unapproved drugs into the U.S. and sold them to the growing number of AIDS patients who had virtually no treatment options, as the dis­ease was so new.

But it’s not just the movie and the Goldwater group. Also urging the Right to Try movement forward is a confluence of other factors, said Ross Upshur, director of the University of To­ronto Joint Center for Bioethics, and a member of the World Health Organization’s committee looking at compassionate use for vaccines.

“The pipeline is choked with bureaucracy, then add Google and the internet, and sudden­ly not only is everyone a doctor, but everyone is also a researcher and a scientist,” he said. “This has changed the landscape dramatically. The person with the disease, or their family, will comb the internet and can come to know more about the disease than their doctor ever will, and that’s where you run into Right to Try.”

The case of Joshua Hardy received a lot of at­tention last year. Joshua is a now 8-year-old-boy who contracted a life-threatening adenovirus infection following a bone marrow transplant to treat his cancer. The standard-of-care drug being used to treat his infection was harming his kidneys, so he had to be taken off the drug. His family learned of the biotech company Chimerix’s compound Brincidofovir, an anti-viral agent designed to avoid harm to the kid­neys. The drug was in phase III trials focused on a different type of infection.

The family asked Chimerix to provide ac­cess to the investigational drug for Joshua. The company initially said no, fearing that the drug’s clinical trials would be undermined. The Hardy family went public with the company’s refusal, and it became a storm on social media as well as in traditional press outlets, ultimately resulting in death threats to Chimerix’s CEO. The company responded by creating a new clinical trial that focused on Joshua’s illness. He participated, and ultimately recovered.

Upshur thinks the Right to Try movement will pick up even more steam as more break­throughs occur in precision medicines that are targeted to receptors rather than diseases.

This year, Johnson & Johnson reached out to bioethicist Art Caplan to find a good way of dealing with Right to Try, since Caplan—founding director of the Division of Medical Ethics in NYU Langone Medical Center’s De­partment of Population Health—leads the only independent group tracking Right to Try and compassionate-use issues.

The problem for drug makers? The patients who know how to wage a social media cam­paign and press the hardest—like the Hard­ys—are most likely to get access to the drugs, while the quieter ones are not, said Caplan. J&J wanted to even that out, so Caplan helped set up a committee and a system for handling re­quests anonymously.

“There’s no lobbying the members or call­ing the chair,” he said. “This makes it fairer for everyone.”

Caplan says he foresees more sponsor com­panies setting up such committees, as the num­ber of Right to Try requests picks up. Others note that sponsors could benefit by gathering additional data about investigational drugs un­der Right to Try programs if they had the infra­structure to do so.

Potential harms

Research sponsors are thinking things through.

Caplan predicts that companies will begin manufacturing larger quantities of investiga­tional treatments and put some aside for Right to Try requests.

Several sponsors are considering charging patients to help defray the increased manufac­turing and distribution costs.

But what of the harm that investigational drugs can cause? That’s what worries Upshur.

“There’s a big misconception here: that we have miraculous cures in trials, when only some­thing like one in 100 of the compounds in tri­als will make it through phase III, and these compounds have equal capacity to do harm as to do good,” Upshur said. “There’s a very good reason the regulations are in place: to protect people from possible harm while we make that assessment.”

There’s a lot of press as each new state passes a Right to Try law, but Caplan says he doesn’t think it will result in any great shift in the way the industry conducts itself. After all, federal regulations already exist via the FDA that does much the same thing.

“The new laws don’t create an obligation for companies to give anything to patients, rather, it offers patients a right to beg, which they had anyway through the FDA’s expanded pro­gram,” said Caplan.

And the FDA recently made some changes to its expanded access program to make it quicker and more responsive, with less paper­work, and with doctors making the decision, not the FDA, said Caplan. The vast majority of requests for investigational drugs for termi­nal patients are granted, so the agency is not a roadblock, as the Goldwater Institute might have the public think, he said.

“As far as I’ve been able to tell, the Right to Try movement is just a public relations cam­paign criticizing the FDA, perhaps with the goal of trying to get the government to do something to speed up the drug approval pro­cess overall,” Caplan said. “But it does send a message from the grassroots level that people are interested in doing something about this.”

With this ironic twist, he added, “The people pushing these laws are the same people who are pro-business, so these laws don’t obligate drug companies to give patients their compound for free, nor do they offer help with travel or get­ting to the drug,” Caplan said. “They won’t go there.”

At the end of the day, the drug approval and commercialization process is regulated by the FDA. “However well intentioned,” said PhRMA’s Haverfield, “legislation at the state level isn’t likely to add any meaningful new approaches that can optimize the federal gov­ernment’s expanded access process overseen by FDA.”

Will Right to Try laws result in terminally ill patients getting fast access to experimental drugs? The jury is still out. No one has yet taken advantage of a Right to Try law.

Stay tuned.

 

Suz Redfearn is an award-winning jour­nalist and former senior staff writer for ClinPage.com. Her articles have appeared in numerous publications, including the Atlan­tic.com, the Washington Post, Slate, Salon, Politico, Men’s Health, MedPage Today and Physicians Practice. Suz holds a journalism degree from Loyola University in New Orleans. Email suzredfearn@gmail.com.

This article was reprinted from Volume 22, Issue 07, of The CenterWatch Monthly, an industry leading publication providing hard-hitting, authoritative business and financial coverage of the clinical research space. Subscribe >>

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