On May 30, 2018, President Trump signed into law the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 (Pub. L. No. 115-176) (the “Right to Try Act”), which creates a new regulatory pathway for drug companies to provide investigational drugs to patients suffering from life-threatening diseases. Under the Right to Try Act, drug manufacturers may make eligible investigational drugs available to eligible patients without preapproval by the Food and Drug Administration (“FDA”), and without following the generally applicable requirement that an institutional review board (“IRB”) review and approve the use of the investigational drug. The Right to Try Act does not modify or supersede any existing FDA expanded access programs (also known as “compassionate use” programs), and does not obligate drug companies to grant access to investigational drugs. Because drug companies have sole discretion to decide whether to make eligible investigational drugs available under the Right to Try Act, they should understand and carefully evaluate how this legislation differs from current law, including the differences in regulatory and ethical safeguards between the Right to Try Act and current FDA regulations.
Recent Efforts to Promote Access to Investigational Drugs
In recent years, Congress and FDA have taken a series of actions to facilitate patient access to investigational drugs, including streamlining existing expanded access programs, reducing administrative burdens and delays, and increasing the visibility and transparency of companies’ expanded access programs. In September 2007, Congress required sponsors of most controlled studies of investigational drugs to specify in a clinical trial record submitted to the National Institutes of Health for posting on www.ClinicalTrials.gov whether expanded access to the drug is available and, if so, how patients can obtain additional information about such access. (Food and Drug Administration Amendments Act of 2007, Pub. L. No. 110-85, § 801, 121 Stat. 823, 904-22 (2007).) In December 2016, Congress enacted the 21st Century Cures Act, which requires that manufacturers of investigational drugs for serious diseases post their policies for evaluating and responding to expanded access requests on a publicly available website. (21st Century Cures Act, Pub. L. No. 114-255, § 3032, 130 Stat. 1033, 1101 (2016).)
FDA has also taken a number of steps to streamline the administrative procedures for regulatory review of requests to access investigational drugs. In 2009, FDA overhauled its expanded access regulations, clarifying the criteria that must be met to authorize expanded access use, the required contents of expanded access submissions, and the regulatory and ethical safeguards that must be in effect to protect patients. (Expanded Access to Investigational Drugs for Treatment Use, 74 Fed. Reg. 40,900, 40,900 (Aug. 13, 2009) (codified at 21 C.F.R. pts. 312 & 316).) In August 2017, FDA added a new section to its Manual of Policies and Procedures to describe a process by which physicians can request emergency use of investigational drugs for individual patient expanded access after normal FDA business hours. (“Emergency Investigational New Drug Application Process During and After Normal Business Hours” (August 2017).) And in October 2017, FDA announced policy changes intended to ease the process for applying for expanded access use of investigational drugs and devices. (“Expanded Access to Investigational Drugs for Treatment Use—Questions and Answers” (October 2017).) In particular, FDA decreased the administrative burden of IRB review by permitting the IRB chairperson or designee to approve the expanded access use, rather than the full IRB committee. (Id.) FDA also addressed manufacturers’ concern that adverse events from expanded access use could impede the company’s development program for the investigational product by indicating that adverse event data rarely are reflected in product labeling or lead to a clinical hold determination. (Id.)
Summary of the Right to Try Act
Despite the recent legislative and regulatory reforms described above, proponents of right to try laws have argued that FDA regulations have continued to restrict or delay access to promising new treatments. These arguments resonated in state houses across the country, resulting in 41 states enacting right to try laws beginning in 2014. (“Right to Try in Your State” (last visited July 19, 2018).) Recognizing that state laws could not preempt federal law enforced by the FDA, however, right to try proponents also advocated for changes in federal law and policy. Those efforts culminated in the passage of the Right to Try Act, which expressly states that it is an “alternative pathway alongside, existing expanded access policies.” (S. 204, 115th Cong. § 3 (2018).)
Under the Right to Try Act, to be eligible to access an investigational drug, a patient must: (i) be diagnosed with a life-threatening disease; (ii) exhaust all approved treatment options and be unable to participate in a clinical trial for the investigational drug; and (iii) provide written informed consent for the use of the investigational drug. Only certain investigational drugs are eligible for distribution under the Right to Try Act, however. Specifically, an “eligible investigational drug” must:
- Have completed a phase 1 clinical trial;
- Not be approved or licensed for any use;
- Be subject to either (a) a filed new drug application or biologics license application or (b) an investigational new drug (“IND”) application and be intended to form the primary basis of effectiveness in support of product approval or licensure; and
- Be under active development or production and not discontinued by the manufacturer or placed on clinical hold.
The Right to Try Act establishes liability protection for drug companies that receive a request for an investigational drug. If a company declines to grant a request, the Right to Try Act provides the manufacturer with immunity from liability. Similarly, if a company agrees to provide access and complies with the Right to Try Act, the manufacturer will not be liable for any related act or omission.
Whereas existing expanded access programs remain subject to the Federal Food, Drug, and Cosmetic Act and its implementing regulations, the Right to Try Act largely exempts expanded access from existing FDA requirements and instead establishes a new regulatory framework. A manufacturer that provides an investigational drug under the Right to Try Act must report to FDA, among other information, known serious adverse events on an annual basis (as opposed to the general IND requirement of within 15 days of the sponsor determining that the event is reportable) and must obtain from the subject written informed consent. The manufacturer must continue to satisfy three current FDA regulations that (i) prohibit the promotion of the investigational drug, (ii) require certain labeling that describes the drug as investigational, and (iii) limit the amount that can be charged for the investigational drug.
The use of an investigational drug under the Right to Try Act is also exempt from IRB oversight. In general, IRBs review and approve the study protocol and consent form to ensure that, among other things, human subjects are protected and the risks of the investigational drug are minimized and adequately disclosed. Manufacturers that seek to retain IRB involvement over expanded access use as a patient protection safeguard should consider how the Right to Try Act varies from other expanded access programs.
The Right to Try Act also limits how FDA may use outcome data from a Right to Try Act program. FDA is prohibited from using a clinical outcome associated with a Right to Try Act use to delay or adversely affect the review or approval of a marketing application for the drug, except in two circumstances. First, the manufacturer may request that FDA use the outcome data for such purposes. Second, FDA may determine that the use of the outcome data is critical to evaluating the safety of the investigational drug. Notably, this statutory provision does not affect whether FDA can rely on outcome data from a Right to Try Act program to impose a clinical hold on an ongoing clinical trial involving the investigational drug.
Implementing the Right to Try Act
FDA has publicly announced plans to assemble an internal working group to evaluate how to implement the Right to Try Act, and to issue guidance to clarify and interpret certain statutory provisions. In the meantime, drug manufacturers are likely to face requests for access to investigational drugs under the Right to Try Act. Drug companies should therefore assess how the Right to Try Act relates to their existing expanded access programs and whether making drugs available under the new statute would be compatible with the balance the company has struck between providing access to promising investigational drugs and ensuring appropriate patient safeguards, including FDA and IRB oversight. In certain circumstances, FDA review may serve a valuable patient protection role. Although a company will be aware of nonpublic nonclinical and clinical information specific to its product candidate as well as published literature on the drug, FDA can be uniquely positioned to be aware of class-wide concerns that may not be known to individual companies.
Many companies have put considerable effort into establishing processes and guidelines for decision-making in this area, and take a degree of comfort in the added layers of oversight afforded by IRB and FDA review. Such companies may be reluctant to adopt the new statute’s end-run around these established procedures, potentially putting patients at increased risk of harm, particularly if they perceive the current procedures as working well. One near-term issue that drug manufacturers will need to grapple with is whether to address the Right to Try Act in their public descriptions of their expanded access programs. While this level of detail is not mandated by the 21st Century Cures Act or the Right to Try Act, companies are likely to receive inquiries about the new law. Thus, companies will likely need to have a position on the Right to Try Act in the relatively near future, regardless of whether they choose to post that position publicly or address it non-publicly through an internal policy or on a case-by-case basis.
The Right to Try Act appears to reflect a growing trend in which patients are demanding earlier access to drugs they believe hold promise, even without substantial evidence of effectiveness and before the full safety profile is known. Patient-focused drug development programs, under which patients contribute to FDA’s understanding of the benefit and risk considerations, are helping to move the needle toward patients assuming more risks of an unsafe or ineffective drug in exchange for accessing the drug earlier in its clinical evaluation. For example, under the 21st Century Cures Act, FDA is required to issue new guidance regarding methods and approaches to be used in capturing and measuring patients’ experiences and perspectives. Although the courts have held that terminally ill patients do not have a constitutional right to access experimental drugs (see, e.g., Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach 495 F.3d 695 (D.C. Cir. 2007)), Congress and, to some extent, FDA, seem to be sympathetic to allowing seriously ill patients the ability to access experimental drugs sooner in the development process when there are no comparable alternatives, when preliminary safety information is available, and when adequate patient safeguards are in effect.
The growing momentum towards broader access to investigational drugs is likely to continue placing a heavy burden on drug companies. As pressures continue to mount on manufacturers to make investigational drugs available, companies will need to balance such requests with competing considerations, including assuring that any decision to provide experimental medicines is made in a manner that is scientifically, clinically, and ethically sound. While such considerations may sound self-serving to those who do not have to make them, the experiences of those responsible for such decision making proves demonstrably otherwise, as illustrated by the procedures and safeguards, including use of third party advice in many cases, that drug manufacturers have developed to assist in reaching fair and appropriate determinations in such matters. The movement towards freer access to unapproved therapies also raises questions not addressed by the Right to Try Act, including whether payors (commercial and government-funded) will provide coverage for investigational drugs accessed through the Right to Try Act.
In short, while the Right to Try Act is the latest development in the debate over patient access to investigational therapies, it is unlikely to be the last.
Greg Levine, Mark Barnes, Abram Barth, and David Peloquin are attorneys, and Ahsin Azim is a law clerk, with Ropes & Gray LLP.
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