A Brief History of Expanded Access (Pt. 2) 2014 – 2020

2014 — Colorado State first to adopt the Right to Try Act

Colorado became the first state to pass a Right to Try law in May of 2014. This law gave terminally ill patients the right to use investigational drugs outside of the purview of the FDA. At the time, these laws were being advanced in several states by patient advocates who were frustrated by the amount of time the federal approval process took to access investigational drugs. Missouri, Louisiana, and many other states followed suit. This controversial piece of legislation would later go on to be passed at the federal level. The law made provision for patients to access investigational drugs as early as after completion of phase 1 of development (i.e. in the absence of efficacy data). Opponents of the Right to Try Act were of the opinion that this was an ill-advised effort that circumvented federal law while also undermining the drug development process. They felt that the law threatened to harm more people than it helped by providing access to medications that have not been proven to be safe and effective.

In the United Kingdom, the Early Access to Medicines Scheme (EAMS) was introduced. EAMS is intended to treat, diagnose, or prevent seriously debilitating or life-threatening conditions. Doctors are allowed to use the scheme (when no other adequate treatment is available) to access new unlicensed and off-label drugs for eligible U.K. patients who have a high unmet medical need.

The Ebola Crisis in West Africa began in 2014, leading the World Health Organization and Ebola Taskforce together with several governments to advocate for the use of investigational drugs through Expanded Access Programs to treat Ebola patients.

2016 — From Washington, D.C. to Europe, new policies emerge

Certain patient advocates had widely claimed that filing paperwork for Expanded Access routinely took over 100 hrs. In response, the FDA removed some of the Expanded Access-related questions from the IND application form and created Form 3926. The agency claimed they streamlined the process and reduced the time needed to complete it to 45 minutes.

It also updated the final guidance on “Charging for Investigational Drugs under an IND.” This added valuable relevant information to the agency’s “Regulation on Charging for Investigational Drugs under an IND for either Clinical Trials or Expanded Access for treatment use.”

Further, an important step was taken to simplify the process for physicians seeking access to an investigational product to treat their patients. Only one Institutional Review Board member —the Chair or another appropriate person — could now approve the treatment. The FDA believes that this improved process expedites the facilitation of access while still protecting patients.

The 21st Century Cures Act was passed in response to the Right to Try Act. This legislation required drug developers to disclose their Expanded Access Policy on the Clinical Trials database, ClinicalTrials.gov, as well as publish their policy on their website. These requirements were embedded in the Final Rule.

The European Medicines Agency (EMA) launched the Priority Medicines Scheme (PRIME) in 2016. PRIME is designed to optimize the drug development process to allow patients to benefit as early as possible from novel therapies. These therapies must address an unmet medical need and their path to market authorization is expedited based on early clinical data.

2017 — FDA revises guidance on adverse events and launches “Expanded Access Navigator”

The FDA released final guidance on Expanded Access for the industry entitled, “Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers.” In this revised guidance, the FDA clarified how adverse event data from Expanded Access would be considered in the drug approval process and clarified which other factors the agency would consider in the review process.

This came after a U.S. Government Accountability Office (GAO) report highlighting stakeholder issues such as the patient and physician journey. It found that while the FDA had taken steps to improve the Expanded Access Program, it still needed to further clarify how adverse events data were viewed. Drug developers and sponsors often indicate they are fearful of being issued a clinical hold order because of adverse events from Expanded Access Programs.

The Reagan-Udall Foundation, a non-profit organization created to help the FDA accomplish its mission, launched an online “Expanded Access Navigator” to help patients and physicians understand the processes and programs associated with Expanded Access.

Around the same time, the European Organization for Rare Diseases (EURORDIS) issued a report called  “Early Access to Medicines in Europe – Compassionate use to become a reality.” It argued for Compassionate Use Programmes for medicines to be made more widely available to those patients in need of urgent help. In addition, EURORDIS recommended that the EU adopt the French ATU system or adopt an EU Regulation which would confer a greater role to the EMA in the organization of Compassionate Use programs.

Meanwhile the Italian government, under Ministerial Decree, issued new rules on Expanded Access to medicinal products. These stated that Expanded Access may be sought for non-authorized products. It thus allowed Expanded Access requests to be sought for non-authorized products, as well as for medicinal products that are authorized in Italy or abroad and used for an off-label indication. It also made provision for the use of drugs that were authorized abroad but not yet in Italy. Expanded Access may also be requested for advanced therapy medicinal products (ATMPs) such as gene and cell therapies.

2018 — FDA’s response to the Federal Right to Try Act

The Right to Try Act, or the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act, was signed into law on May 30, 2018. This law potentially provides another way for patients who have been diagnosed with a life-threatening disease, have tried all approved treatment options, and are unable to participate in a Clinical Trial, access to certain pre-approval treatments.

The whole movement was backed by the Goldwater Institute, a libertarian think-tank from Arizona. The passage of the Right to Try Act renewed public interest in how patients might gain access to therapeutic options. This legislation created an alternative pathway to the FDA’s Expanded Access regulations and ostensibly another way for patients to access drugs that are still in development. Many controversies surround its implementation, chief amongst these is that the law allows physicians and drug companies to implement an investigational treatment protocol without, or with limited, external oversight.

In November of this year, the FDA organized a workshop around Expanded Access and leveraging treatment data, hosted by the Reagan-Udall Foundation. During this public meeting, FDA officials stressed that data collected by sponsors and their Expanded Access programs are useful in supplementing Clinical Trial data and may help inform regulatory decision-making. Panellists advocated for a flexible and case-by-case approach from the agency rather than establishing a new regulation.

The long-awaited “Expanded Access Program report” compiled by McKinsey & Co was released in 2018. This report highlighted that the multi-stakeholder environment as well as the absence of standard processes and policies, created confusion around Expanded Access. It also found that drug developers reported challenges particularly related to uncertainty about how the FDA uses adverse event data from Expanded Access Programs. Additionally, they reported difficulty in managing divergent requirements and guidance from foreign health authorities.

2019 — Project Facilitate aims to improve access to investigational cancer drugs

Project Facilitate was launched by the FDA. The pilot project established a call center as a single point of contact for physicians to submit single-patient Expanded Access requests for oncology patients. In addition, then-FDA commissioner Scott Gottlieb issued a statement on Post-Trial Access (PTA) encouraging developers to use the Expanded Access mechanism to allow promising drugs to continue to be provided to patients after the completion of a Clinical Trial.

Another GAO report was released. It highlighted that drug developers and other stakeholders were largely supportive of steps taken by the FDA to facilitate access to Investigational New Drugs through Clinical Trials, Expanded Access, or Right to Try requests. The report looked closely at actions the FDA had taken to broaden Clinical Trial eligibility criteria, improve access to Investigational Drugs outside of Clinical Trials as well communicate with patients.

2020 and beyond — Expanded Access increasingly becomes a public health priority

Public health emergencies such as the Ebola crisis and the ongoing COVID-19 pandemic, have prompted governments as well as global health organizations, such as WHO, to increasingly recognize the importance of Expanded Access as a mechanism for access. The urgency and severity of the COVID-19 pandemic have bolstered the acceptability and utility of Expanded Access globally. In a similar fashion to the AIDS epidemic in the 1980s, global health organisations as well as regulatory authorities are now having to balance concerns such as scientific process and patient safety against an urgent duty of care.

Expanded Access continues to evolve in response to a wide range of signals and triggers from a variety of stakeholders across disparate disease areas. While regulatory authorities in different parts of the world may have varying approaches to developing and implementing Expanded Access mechanisms, it is clear that processes, programs, and initiatives that credibly engage all stakeholders are more likely to have the most benefit for patients.