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Pink Sheet – 'Right To Try' And PDUFA VI: Patient Advocates, Industry Fight Senate Add-On

Pink Sheet – 'Right To Try' And PDUFA VI: Patient Advocates, Industry Fight Senate Add-On

Executive Summary

Given that ‘right to try’ is intended to be a patient-centered proposal, patient organizations are a strong voice in opposition, working behind the scenes to revise – or entirely exclude – the legislation as part of the user fee package. But the bill also has powerful advocates among Senate Republicans and in the Trump Administration.

Patient advocates are working with Congressional staff to revise proposed federal “Right to Try” legislation that would prohibit the US FDA from taking any action to restrict compassionate use programs in the 34 states that allow it.


Opponents to the measure – including Friends of Cancer Research, the American Cancer Society and the National Organization for Rare Disorders – argue that the while the sentiment of “right to try” is well-meaning, the proposed federal legislation (S. 204, known as the “Trickett Wendler Right to Try Act”) fails to adequately protect patients.


Pushback from patient advocates had an early success in keeping “right to try” out of the preliminary discussion draft of the FDA Reauthorization Act (FDARA) of 2017, which combines user fee programs for drugs, biologics, generics and medical devices. The question is whether it will stay out, now that Congress is starting to look at legislative add-ons.


The first draft of FDARA is the simplest possible reauthorization: it includes legislative language for each of the four core medical product fee programs and reauthorization of a handful of other programs that share the Sept. 30 sunset date. The first draft is “clean”: There are no policy riders included – nor are there any placeholders for coming legislation. (Also see “First Draft FDA User Fee Bill Is Squeaky Clean” – Pink Sheet, 14 Apr, 2017.)


FDARA is not expected to remain clean for long. The House Energy & Commerce Subcommittee on Health held a hearing May 2 to consider four medical device bills as potential add-ons: Over-the-Counter Hearing Aid Act of 2017 (HR 1652); Fostering Innovation in Medical Imaging Act (H.R. 2009); Medical Device Servicing and Accountability Act (H.R. 2118); and H.R. 1736, to improve the process for inspections of device establishments and for granting export certifications. (Also see “Bill Bonanza: US Congress Sprouts Medtech Legislation This Spring” – Medtech Insight, 2 May, 2017.)


While the initial focus is on devices, opening up an otherwise clean reauthorization increases the probability that drug-related measures could be tacked on as well. In addition to “right to try,” legislative responses to generic drug prices (incentives like priority review vouchers and/or removal of barriers like limited distribution) are among items very likely to be considered in that process.


Another key test of FDARA’s cleanliness will be the markup in the Senate HELP Committee, scheduled for May 10.


Given that “right to try” is intended to be a patient-centered proposal, patient organizations are a strong voice in opposition. But the bill also has powerful advocates among Senate Republicans – including the bill’s sponsor, Sen. Ron Johnson (R-Wisc.) – and in the Trump Administration, particularly from Vice President Mike Pence. (Also see “‘Right to Try’ Has White House Support: Add-On To PDUFA Looks Tough To Stop” – Pink Sheet, 9 Feb, 2017.)


In one positive sign for opponents to “right to try,” President Trump’s nominee for FDA Commissioner Scott Gottlieb declined to directly endorse the pending federal legislation in a carefully worded response to questions submitted by Sen. Patty Murray (D-Wash.) after his April 5 HELP Committee confirmation hearing. (See sidebar for related story.)

As a cancer survivor, Gottlieb said he identified with patients’ desire to access investigational treatments. But he also was non-committal on alternatives, simply stating that he would be willing to work with Congress as it considers “right to try” proposals. Gottlieb’s nomination cleared the HELP Committee on April 27 by a relatively partisan 14-9 vote. (Also see “Gottlieb Advances, But FDA’s Future Seems Increasingly Partisan” – Pink Sheet, 27 Apr, 2017.)


Should Trickett Wendler Act be destined for inclusion in the user fee reauthorization, opponents to the measure believe changes are needed. Friends of Cancer Research would like to see modifications that address two key issues: (1) transparency and (2) informed consent.


In an editorial to the Health Affairs blog, “How Do We Protect Patients From False Promises In Right-To-Try Laws?,” Friends Founder Ellen Sigal argues that “serious changes … are needed before this law is safe for patients.” Provisions for informed consent are “essential” and would guarantee that patients requesting expanded access can “judge the magnitude of their decision to use an unapproved drug,” Sigal says.


Second, she notes that neither existing state laws nor the proposed federal legislation require companies from provide experimental drugs under expanded access. While companies have good reasons for restricting access, Sigal said, “the limits of Right to Try must be clear.”


Along with most patient groups, the majority of those in the medical community – including drug companies and former FDA officials – are united against passage of a federal “right to try” effort. While opponents to Trickett Wendler agree that compassionate use programs should be made available in certain situations, they argue that removing FDA from the process is not in the best interest of patients. (Also see “‘Right To Try’ Bill Contradicts US FDA’s Mission, Former Official Says” – Pink Sheet, 14 Mar, 2017.)

‘Ripple Effect’ From One Firm’s Bad Publicity

Drug sponsors are especially leery of “right to try” legislation. Many companies – especially smaller firms – do not have the resources to run an expanded access program, nor are they always able to manufacture the additional drug supply needed to treat those patients. By focusing on removing FDA from expanded access approval process, “right to try” advocates incorrectly assume that the agency is the bottleneck in clearing requests for compassionate use, when in fact 99% of requests are approved within four days (and within 24 hours for emergency requests).


There are also public relations risks with being on the wrong side of an expanded access request. During a panel discussion on “right to try” at the World Orphan Drug Congress in Washington, D.C. April 21, Biotechnology Industry Organization SVP-Science Policy Kay Holcombe recalled Chimerix Inc.’s experience with its experimental anti-viral drug, brincidofovir, after the company initially refused an expanded access request from 7-year-old cancer patient in 2014. (Also see “Chimerix And FDA’s Compassionate-Use Solution” – Pink Sheet, 26 Mar, 2014.)


The social media firestorm that followed – including death threats to then-CEO Ken Moch, who left the company as a result – led Chimerix to reverse its decision and allow access. The patient, Josh Hardy, was successfully treated for his infection, and the resulting cheers on social media lifted Chimerix’ stock price by nearly 50 percent. But the entire experience had a “ripple effect” across BIO members companies, Holcombe said, and has only dissuaded other small manufacturers from following suit.


NORD Associate Director for Public Policy Paul Melmeyer agreed, stating that “right to try” measures will not increase patient access to effective treatments, and may end up harming the system. If FDA is removed as a partner in the process, “companies that are currently offering expanded access program may be less willing to offer them in the future,” he said at the World Orphan Drug Congress. Manufacturers also may be unwilling to participate in programs that are seen as “antagonist” to FDA.

The Cures Defense

One other avenue for manufacturers to fend off more legislation in the space is to demonstrate progress from newly enacted expanded access provisions included in the 21st Century Cures Act. Trickett Wendler failed to garner enough support for inclusion in the Cures Act last year. Rather than making any changes to FDA policy in the space, a provision of the Cures Act requires manufacturers to develop an expanded access program and publicize it in some way (such as a web site posting) with contact information for interested patients. That requirement went into effect in February.


Manufacturers are complying with the “Cures” provision, with some taking it a step further. For example, Shire PLC SVP and Head of Global Clinical Development Howard Mayer reported that his company’s compassionate use policy and email portal is up and running, with a 72-hour turnaround on expanded access requests. Once a request comes in, Mayer calls a meeting with the clinical, regulatory and safety leads and responds to the patient directly via written correspondence.


“There are certain circumstances under which early access makes sense,” he said. Rather than forcing another legislative solution, manufacturers should be encouraged to anticipate when a drug under development might receive an expanded access requests, Mayer suggested. Shire has received “numerous requests” for compassionate use of maribavir, which is in Phase III studies for cytomegalovirus post-bone marrow or organ transplant.


In response, Shire established a parallel program for patients with CMV infection that do not meet the inclusion/exclusion criteria. The company will use a similar strategy for idursulfase-IT, which is in Phase III studies for the treatment of neurocognitive decline in its Hunter syndrome, should results be positive, Mayer said.

Improving FDA’s Educational Role

NORD suggested that the current expanded access program could be strengthened to better educate physicians and patients about how to access unapproved treatments. FDA could better clarify its role in the process, Melmeyer said, adding that a “more accessible” office within the agency would help. “We are getting a lot better at this as we continue to debate expanded access, but we still aren’t reaching as many patients as we could.”


FDA has publicly proposed creating an Office of Patient Affairs to centralize patient engagement activities across the different centers, which could begin to address NORD’s concerns. (Also see “US FDA Plans New Office Of Patient Affairs” – Medtech Insight, 13 Mar, 2017.)


A separate effort to expand compassion use is the Reagan-Udall Foundation’s development of an Expanded Access “Navigator,” which would offer a central, Web-based location for physicians and patients to find the appropriate contact within companies to request access to an investigational drug. (Also see “Expanded Access Programs Need FDA Policy Changes To Really Expand” – Pink Sheet, 23 May, 2016.)


One working group out of the New York University School of Medicine authored a three-page proposal at the request of lawmakers on Capitol Hill interested in finding ways to improve the current system. The working group includes President and CEO of Parent Project Muscular Dystrophy Pat Furlong and NYU School of Medicine assistant professor research in the Division of Medical Ethics Alison Bateman-House.


The working group outlined five key steps to improve patient access to unapproved medicines while at the same time making such access “appealing and practical” to drug companies. They include strengthening FDA’s expanded access program, clarifying FDA’s authority over unapproved drugs and exploring ways to encourage companies to participate. The paper could be used as a blueprint for improving expanded access, should efforts fail to attach Trickett Wendler to the user fee authorization.…