Working group to tackle regulatory and ethical issues around CGT expanded access
Also known as compassionate use, expanded access allows patients, who are seriously or terminally ill, who have exhausted all available treatment options, to access investigational treatments outside clinical trials.
“The impetus for the working group comes from increased patient and developer interest in pre-approval access to investigation products in the CGT space," said Patricia J Zettler, associate professor of law at The Ohio State University, and chair of the new working group.
Demand for compassionate use is expected to continue or even accelerate. One major reason for this is that the FDA is no longer exercising enforcement discretion for premarket approval requirements for regenerative medicine products, said the ISCT.
Inappropriate use of this pathway, however, could harm the entire CGT sector, undermine research efforts, and ultimately delay approval of products critical for many patients, it cautioned.
The ISCT Expanded Access Working Group aims to:
- Provide resources that help all CGT stakeholders and regulators to provide expanded access in ways that serve the interests of patients without undermining rigorous research.
- Identify and address practical, ethical, and regulatory issues that arise from the use, and potential misuse, of the established expanded access pathway.
- Develop a code of ethics for CGT stakeholders using expanded access and seeking endorsement from societies and professional organizations in the field.
Zettler told BioPharma-Reporter: “ISCT is the leading organization in the cell and gene therapy (CGT) space and works with a variety of stakeholders. It is not interested in acting as a police force but is interested in considering the ways that cell and gene therapies can be most efficiently developed into safe and effective therapies for patients and ways to help stakeholders do that.
"There has been more commercial or financial interest in the expanded access space, which may raise questions about how to ensure that patients have access to investigational products outside clinical trials in the rare circumstances when that is necessary while also balancing the need to ensure that studies can go forward and that robust scientific evidence can be developed."
Patients and their physicians are also supported in their demands for pre-approval use of investigational drugs and interventions by recent changes in the US legislative landscape to allow new avenues of access, such as the Right to Try platform, with US President Trump signing that into law in 2018, noted Zettler.
"Some US states have passed Right to Try laws that are specific to stem cells."
In terms of the expanded access platform, its use was prominent during the pandemic, she noted, with some patients obtaining certain investigational COVID-19 products that way.
"As the CGT field becomes more mature and hopes around such therapies start to be realized, interest in expanded access [for such investigational interventions] will only increase," she added.
Risk: Interference with FDA approval
A research paper, looking at the benefits and challenges around expanded access in the US noted a major concern is that access to an investigational treatment might interfere with its US Food and Drug Administration (FDA) approval.
“Patients requesting access to a drug under development are usually frailer, given the advanced stage of their disease and the multiple lines of prior therapy. Therefore, they are at high risk of toxicity. Once reported to the FDA, these events might ultimately negatively affect the approval process. Additionally, participation in clinical trials might be jeopardized if a drug is easily accessible through an expanded access program.”
The ISCT also outlined how misuse of expanded access in the US could have international repercussions. The working group intends to evaluate expanded access against similarly intentioned programs in other regions and other regulatory frameworks, and research and monitor global developments across the field.
“it is not a US only issue. Our working group is starting by looking at the expanded access pathway specifically in the US. But I think there are implications for the global marketplace. Other parts of the world have similar programs that allow pre-approval access so lessons that can be learned in the US will be relevant for regulators around the world,” commented Zettler.
Indeed, a roundtable session at ISCT's annual meeting in San Francisco in May 2022, will focus on the complex ethical and regulatory issues that arise from the use, and potential misuse, of expanded access pathways, and it will include the participation of global stakeholders. "We are hoping to learn from that international context and use that to move our thinking forward."
The ISCT annual meeting will also serve as a vehicle to kickstart the work of the task force.
Who else is in the task force?
As well as Zettler as chair, the ISCT expanded access working group’s membership includes Laertis Ikonomou, The State University of New York, Buffalo, US, Aaron Levine, Georgia Institute of Technology, US, Bambi Grilley, Baylor College of Medicine, US, Karen Nichols, Vertex Pharmaceuticals, US and Leigh Turner, University of California Irvine, US.
Wilson Bryan, director of the Office of Tissues and Advanced Therapies (OTAT), will serve as the FDA liaison to provide regulatory expertise where relevant.