Enacting a federal right-to-try law that circumvents FDA’s oversight of access to unapproved therapies no longer looks like a sure bet. Still, the debate over right to try has stimulated initiatives to give more patients who have run out of alternatives the chance to try experimental drugs and medical devices.
Propelled by victories in 34 states and endorsement of their cause by President Donald Trump, Vice President Mike Pence and 46 senators, patient advocates and libertarian activists pushing for federal right-to-try (RTT) legislation believed in January that victory in Congress was imminent. Like other populists who swept into the nation’s capital, they’ve learned that nothing in Washington is as simple as it seems.
RTT proponents had hoped to attach their legislation to user fee reauthorization, which would have been the fastest path to getting an RTT bill to Trump’s desk. While the user fee bills haven’t been finalized, RTT is unlikely to be included, according to congressional staff.
They say proponents will try to hitch RTT to other must-pass healthcare bills, or push it through as a stand-alone law.
Unlike state legislatures where there has been almost no organized opposition to RTT, a broad ad hoc coalition of biopharmaceutical companies, national patient advocacy groups and medical societies has formed to fight federal legislation. These groups believe RTT legislation would harm patients by exposing them to untested therapies and delaying the collection of data that is essential for approvals.
Instead of RTT, they are creating services and advocating regulations and laws that could address many of the concerns from patients that have fueled demand for RTT. The services aim to help patients and physicians navigate the compassionate use process.
Meanwhile, FDA and medical societies are pressuring drug developers to expand entry criteria for clinical studies so patients can access investigational drugs without resorting to compassionate use.
THE LIBERTARIAN ARGUMENT
The RTT movement was conceived of by the Goldwater Institute, a libertarian think tank. The central idea is that FDA should have no role in determining whether patients with terminal conditions who have exhausted all other alternatives can access experimental therapies that have undergone Phase I testing.
Identical RTT bills introduced in the Senate (S. 204) and the House of Representatives (H.R. 878) would bar FDA from restricting access to experimental therapies that have been prescribed by a physician to treat a terminal illness. The therapies would have to have completed Phase I testing and be under development in an FDA-approved clinical trial.
Like state bills, the federal RTT legislation would do nothing to require, coerce or motivate drug sponsors to provide access to unapproved therapies.
The bills would shield manufacturers, physicians and distributors of therapies provided under RTT from liability. They also would bar FDA from using information collected as a result of RTT “to delay or otherwise adversely impact review or approval” of the experimental therapy.
RTT has resonated with conservative Republicans who view it as an opportunity to reduce the role of government in regulating medicine, and among politicians across the political spectrum who are moved by the plight of patients desperate for the chance to save themselves or their loved ones.
The Goldwater Institute has recruited hundreds of individual patients, the Abigail Alliance, and about 15 small patient advocacy groups to lobby for RTT, Goldwater spokesperson Starlee Coleman told BioCentury.
The strongest support has come from the White House. Trump and Pence have made clear that they endorse RTT and believe FDA creates unnecessary barriers to accessing experimental therapies.
Scott Gottlieb, Trump’s nominee for FDA commissioner, offered a bland response to a question about RTT posed to him as part of the confirmation process.
“If confirmed, I would commit to ensuring FDA has the right policies and processes in place to appropriately balance individual patients’ needs for access to investigational therapies while recognizing the importance of maintaining a rigorous clinical trial paradigm for testing investigational products and demonstrating safety and efficacy,” Gottlieb wrote. “I would be happy to work with Congress as it considers Right-to-Try legislative proposals.”
I would be happy to work with Congress as it considers Right-to-Try legislative proposals. – Scott Gottlieb, FDA commissioner nominee
RTT opponents seized on Gottlieb’s failure to repeat Trump’s assertions that FDA should be removed from decisions about compassionate use, while proponents said his comments indicated support for the pending legislation.
Behind closed doors, lobbyists from PhRMA, BIO and a dozen biopharmaceutical companies have told members of Congress that drug developers oppose RTT. They fear it could make it difficult or impossible to enroll patients in controlled clinical trials, and would create tremendous social and political pressure for them to comply with requests for compassionate use even in circumstances where patients are more likely to be harmed than helped.
The National Organization for Rare Disorders (NORD) has lobbied against federal RTT legislation and is one of seven patient advocacy organizations that issued a set of principles for access to unapproved therapies that are in direct conflict with the RTT movement. The others are Alliance for Aging Research, American Cancer Society Cancer Action Network, Friends of Cancer Research, The Leukemia & Lymphoma Society (LLS), Parent Project Muscular Dystrophy (PPMD) and St. Baldrick’s Foundation.
“FDA plays a critical role in assessing the risk/benefit ratio of an unapproved therapy, determining whether clinical trials will not be harmed by access to unapproved therapies, and reviewing data that is collected from the use of the therapy, and must be included in these deliberations,” according to the principles.
These groups also support the review by institutional review boards (IRBs) of all requests for unapproved therapies.
It isn’t a coincidence that the statement was issued on May 2, eight days before the Senate Health, Education, Labor and Pensions (HELP) Committee is slated to vote on components of user fee reauthorization legislation.
“We were hearing from the HELP Committee and others that if we wanted to make a statement this was the time to do it,” Peter Saltonstall, president and CEO of NORD, told BioCentury.
“There is an awful lot of energy to get [RTT] passed,” Saltonstall noted. “The coalition that is opposed to it has a strong enough base to influence the discussion.”
Saltonstall acknowledged that opinion about RTT is mixed among rare disease advocates.
“I am very sympathetic to the patient or mom or dad who have no approved therapy and the patient is going to die and they think there’s something out there they think can help,” Saltonstall said. However, he said, “The majority of our members feel it is better to have FDA in the mix.”
RTT supporter Laura McLinn told BioCentury she is disappointed by PPMD’s endorsement of the principles. McLinn and her son Jordan, who has Duchenne muscular dystrophy (DMD), led the push for enactment of an RTT law in Indiana and have been lobbying for a federal law.
“I don’t think the FDA should be the one to decide if the benefit outweighs the risk,” McLinn said. “I think patients should have that right.”
The majority of our members feel it is better to have FDA in the mix. – Peter Saltonstall, NORD
The success of RTT bills in state legislatures, and stories of individuals who have struggled to obtain experimental drugs, have already led to some modest steps to improve access to unapproved therapies.
One idea is to help patients and physicians navigate the compassionate use process.
Kids v. Cancer operates a compassionate use navigator that provides personal assistance to the parents of pediatric cancer patients and to pediatric oncologists.
The Reagan-Udall Foundation for the Food and Drug Administration announced on Thursday that it will launch a navigator service in June. The navigator will initially focus on cancer, said Ellen Sigal, who is chairman of the foundation as well as of Friends of Cancer Research. It will comprise a website with information about the compassionate use process and a directory of companies that have therapies under development. The directory will provide contact information for making compassionate use requests and information about companies’ policies.
BIO is encouraging its members to provide information for inclusion in the directory, according to Kay Holcombe, SVP for science policy at BIO and a member of the Reagan-Udall Foundation’s board.
Reagan-Udall Foundation also will work with medical societies and patient groups to educate physicians and patients about the compassionate use process, Sigal said. “The big problem today is few know how to access these treatments.”
WORKING ON COMPASSIONATE USE
The New York University School of Medicine Working Group on Compassionate Use and Pre-Approval Access, which includes academic bioethicists, patient advocates and biopharma executives, has denounced RTT and has outlined proposals it believes will improve access to experimental drugs.
These include bringing legislators and biopharmas together to discuss options for mitigating risks to companies posed by compassionate access.
“Legislators should require the FDA to expand its current guidance document on expanded access to include clear, specific information about the consequences of a severe adverse event occurring in the context of expanded access,” Alison Bateman-House, co-chair of the working group, and colleagues recommended in a recent Health Affairs blog posting.
The working group recommends that FDA devote more resources to obtaining data about serious or unexpected safety events from physicians who use experimental drugs.
It also recommends that Congress “give the FDA the authority to investigate the collection and use of outcome and patient-reported data from expanded access cases as a supplement to data gathered from clinical trials.”
The idea is to obtain real-world data on an experimental therapy’s performance in patients who are sicker than those typically enrolled in trials.
The group recommends eliminating the requirement that IRBs approve the use of experimental medicines outside a clinical trial. It noted that IRBs aren’t trained to evaluate such requests and, although they almost always approve them, the need to obtain IRB approval can slow the process.
Finally, the group recommends legislative and other measures to promote access to and equity in clinical trial enrollment. Echoing recent statements from Richard Pazdur, director of FDA’s Oncology Center of Excellence, it says laws and policies should be enacted to reduce barriers to clinical trial participation. In a recent New England Journal of Medicine commentary, Pazdur and colleagues called for broader inclusion criteria for oncology trials.