Proposed reforms for access to investigational individualised therapies in the United States has sparked debate about an individual's right to try medicines before they have been officially approved by regulatory bodies, writes MedicalBrief.
The new US federal frameworks and reforms to expedite the progress of and access to investigational individualised therapies – and essentially bypassing the FDA – is off-track, argue Holly Fernandez Lynch, Steven Joffe, Rebecca Ahrens-Nicklas, and Kiran Musunuru in JAMA Network.
The proposed Right To Try 2.0 law contemplates making unapproved treatments available to patients based wholly on the judgment of sponsors, certifying physicians, and their institutions, reflecting shortcomings associated with recent Chinese examples – and patient deaths, they write.
The past decade has seen tremendous progress in developing individualised therapies, from the first antisense oligonucleotide, milasen, targeting a unique genetic variant in 2018 to the first individualised gene editor, k-abe, in 2025.
Regulatory progress has followed these scientific advances. The first patients were treated under single-patient Investigational New Drug (IND) applications authorised through the Food and Drug Administration’s (FDA) Expanded Access (EA) pathway.
Challenges scaling this approach led the FDA to introduce the plausible mechanism framework, and further reforms have been proposed to facilitate access.
Given the complexity and risk associated with these interventions, the key for any prospective reform is to retain the FDA’s regulatory oversight, a consideration highlighted by recently reported deaths of patients treated with investigational individualised therapies in China, where investigators were permitted to proceed without engaging the national drug regulator.
In June 2026, federal Bills for the Right to Try for Individualised Treatments Act (HR 9190, S 4698) were introduced that would remove the FDA’s critical role.
Although we share the goal of bringing investigational individualised therapies to patients as quickly as possible, Right to Try is the wrong approach.
Access to unapproved therapies
EA allows seriously ill patients to receive investigational drugs as long as the FDA agrees there is no satisfactory alternative, risks and benefits are reasonable, the patient could not obtain the drug in a trial, and providing access will not compromise clinical development.
EA occurs under the FDA’s IND regulations, with all associated safeguards. Although other barriers often impede access, the FDA authorises nearly all EA requests. However, the agency may require modifications based on its expertise and access to confidential information across sponsors.
There is also another pathway under which patients may be treated with unapproved drugs but without first engaging the FDA: Right to Try (RTT). The federal RTT law, passed in 2018, allows patients with life-threatening conditions who have exhausted approved treatment options and cannot participate in a trial to access investigational drugs that have completed phase 1 and are under an active IND.
RTT demands compliance only with FDA regulations governing the labelling and promotion of investigational drugs and limiting charging to direct costs.
RTT is grounded in the compelling notion that “Americans shouldn’t have to ask the government for permission to try to save their own lives” and it is possible that some patients have benefited.
However, assessing the law’s impact – positive and negative – has been hobbled by inadequate reporting requirements.3 All the public knows is that no sponsor to date has requested that the FDA use RTT clinical outcomes data to support its marketing application, which could be interpreted to suggest the absence of patient benefit.
Meanwhile, the FDA also has not used such data in determining a drug’s safety, which could suggest the absence of significant harm or merely that the sponsor’s reporting obligations to the FDA are limited to “known” serious adverse events.
Concern about harms associated with RTT may be mitigated by the fact that most sponsors have found little incentive to use it. However, that is not an ideal approach to protecting patients from careless or disreputable actors.
Proposed federal Right to Try for Individualised Treatments Act
In previous examples, including milasen and k-abe, efforts to provide investigational individualised therapies through the FDA’s EA pathway were streamlined by referencing the backbones of pre-existing drugs, including one already approved and one that had completed phase 1 testing.
Also in both cases, FDA oversight was crucial to ensure that the individualised treatments met proof-of-concept, safety, and manufacturing quality standards consistent with their predecessor drugs.
Notwithstanding the importance of these checks, the federal RTT 2.0 Bill proposes several key changes.
First, it would add a new definition of “eligible patient” for those seeking investigational individualised medical treatments. Patients must have been diagnosed with either a life-threatening condition or a “severely debilitating illness”. They must have “considered approved treatment options,” without having exhausted them, but there is no requirement that trial participation be unavailable, potentially inhibiting research.
They (or a representative) must provide written consent, with the possibility of “additional” witnessed consent that explains currently approved options, provides the patient’s attestation of concurrence with their physician’s assessment that existing options are “unlikely to prolong or improve their life,” and describes potential treatment outcomes.
Second, the Bill would add a definition of “investigational individualised medical treatment” as “a drug or biological product for the patient based on an analysis of the patient’s unique genomic profile”. This definition is broad enough to extend to any product selected after genetic testing, rather than being limited to truly individualised treatments.
Furthermore, there would be no requirement for an investigational individualised medical treatment (or any of its components) to have completed a phase 1 trial and no requirement that there be an IND filed with the FDA.
Third, the proposal would allow manufacturers “in compliance with all applicable Federal assurance laws and regulations” and “operating within an eligible healthcare facility” (defined as operating under “Federal assurance for protection of human subjects”) to make the investigational individualised medical treatment available.
Although probably intended to limit participation to reputable sites, this provision is unlikely to have that effect because assurances are associated with applications for federal funding, apply only in research contexts, and RTT excludes oversight by institutional review boards.
Fourth, the proposed amendments would not impose any reporting obligations around the provision of investigational individualised medical treatments, leaving patients, clinicians, the FDA, and the public in the dark about possible safety issues – a serious concern evidenced by the fact that the recent Chinese deaths came to light more than a year later only through whistleblowers and press inquiries.
Importance of FDA oversight
There is undeniable urgency to bring investigational individualised therapies to patients as quickly as possible. However, recent successes do not support proceeding with minimal regulatory oversight.
To the contrary, success for current and future patients is most likely to be facilitated by close engagement with the FDA, which has the unique breadth of expertise, experience, and access to data needed to maximise benefit and minimise harm.
Yet the proposed federal RTT 2.0 law contemplates making unapproved treatments available to patients based wholly on the judgment of sponsors, certifying physicians, and their institutions, again reflecting shortcomings associated with recent Chinese examples.
Individualised therapies require sophisticated scientific techniques and facilities as well as substantial funds to develop, which may offer some protection against run-of-the-mill snake oil. However, the deregulatory approach advanced by RTT 2.0 is likely to be attractive to those who may perceive it as a lower-cost way to begin research without first securing an IND or who envision concierge treatment of self-pay patients and seek to avoid expensive requirements.
It may also be attractive to some patients with heightened tolerance for risk and uncertainty.
Yet not all of these patients will be able to protect themselves in a regulatory vacuum without IND obligations or phase 1 testing of even a related drug.
A recent national survey from the Goldwater Institute, the organisation behind RTT, found that most respondents agreed that patients with terminal illnesses or rare diseases should have access to the most promising treatments, even before FDA approval, and that it is important for the FDA to update its approval process to accommodate individualised treatments.7
Critically, neither perspective suggests that RTT 2.0 is the only path forward. The FDA has demonstrated openness to new approaches to individualised therapeutics while using its EA pathway to make them available pre-approval.
It is possible, and necessary, to protect patient interests without unduly inhibiting access. RTT 2.0 fails an important element of this test.
Holly Fernandez Lynch, JD, MBE1;
Steven Joffe, MD, MPH1;
Rebecca Ahrens-Nicklas, MD, PhD2;
Kiran Musunuru, MD, PhD, MPH, ML, MRA1
1 University of Pennsylvania, Philadelphia
2 Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
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Girl’s death after first-in-human gene editing sparks investigation
Too many experimental drugs, too many trials, too few patients
FDA passes Vertex’s Casgevy for two-year-olds
FDA approves drug for deadly lung cancer