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Critical Path Institute's 'One to Millions' Initiative

On March 27, 2026, the Critical Path Institute (C-Path) announced the launch of a transformative initiative named "One to Millions". This groundbreaking project represents a global collaboration involving various stakeholders aimed at reshaping the future of personalized medicine on an unprecedented scale. With rapid advancements in technologies, including antisense oligonucleotides (ASOs), genome editing, gene therapies, and RNA-based treatments, the potential for creating precisely targeted therapies for small patient cohorts, even individual patients, has never been greater.

However, existing regulatory and reimbursement frameworks developed for widely applicable drugs have struggled to keep pace, creating a widening gap that hampers patient access to these innovative treatments. In response, the "One to Millions" initiative is developing a framework for credible mechanisms and proof principles for rare diseases as set forth by the U.S. Food and Drug Administration (FDA). This framework will utilize C-Path’s centralized data platform, which meets regulatory standards to support evidence collection, regulatory decision-making, and scalable development pathways.

Dr. Klaus Romero, the CEO of Critical Path Institute, remarked on the significance of this moment, saying, "Words cannot fully convey how critical this moment is for changing lives and realizing the long-awaited vision of innovation. 'One to Millions', created to bring personalized therapies to even more people, is a partnership that could only come about through C-Path. It encompasses a regulatory-ready centralized data platform; a unique pre-competitive space within the entire ecosystem; integrated preclinical, translational, and clinical outcomes alongside patient-level results; practical evidence frameworks for optimizing effectiveness and safety assessment; and the ability to create regulatory-level tools necessary for establishing a continuous learning and confirmation process. Simply put, there is no other initiative like this."

The modernized platform approach introduces essential consistency and reliability into advanced therapeutic technologies. By standardizing manufacturing and testing protocols before market release, it directly addresses the inefficiencies and high costs typically associated with drug development in small volumes. This enables developers to build new therapies based on an established architecture, allowing regulatory reviews to focus exclusively on new components rather than re-evaluating foundational aspects.

Julia Vitarelli, founder of Mila's Miracle Foundation and co-founder of the N=1 Collaborative, emphasized the urgent need for a coordinated approach to address current gaps in the system. "We are living in an incredibly exciting time in genetics. Today, we possess scientific knowledge that can help a vast number of children with severe, life-altering rare diseases, but our access system wasn't designed for the thousands of genetic disorders, each affecting only a small segment of the population," Vitarelli noted. "We are very happy to collaborate with regulatory bodies to shift from approving one drug for one disease to creating processes that work across multiple diseases. This shift could represent a significant breakthrough for millions of patients, but it can only succeed if we ensure continuous, iterative learning from these treatment approaches through systematic data collection and sharing that will serve as the foundation for developing safer and more effective medications."

A key feature of this initiative is the integration of post-approval evidence gathering into the development model. By directly embedding longitudinal registries into this framework, the evidence collected for regulatory decision-making can simultaneously serve as the basis for evaluating durability, safety, and effectiveness from payers' perspectives. Integrating information from the entire ecosystem will prevent duplication of efforts and accelerate the learning process. Dr. Janet Woodcock, former director of the Center for Drug Evaluation and Research (CDER) and former acting commissioner of the FDA, underscored this sentiment, stating, "New technologies allow for potential remedies for the underlying causes of devastating monogenic diseases. However, progress may stall, and regulatory requirements may remain excessively conservative if information for collective analysis and learning is unavailable. We must not repeat past mistakes; we should strive for rapid knowledge transfer and proactive development in this new area by sharing what we have learned. Our patients deserve nothing less."

Leveraging existing resources of preclinical, translational, and clinical datasets will help optimize toxicology and dose selection. Gathering reliable data maximizes the utility of alternative methodological approaches, thereby reducing unnecessary reliance on animal testing while simultaneously building a paradigm of continuous learning and confirmation.

Dr. Timothy Yu, of the Department of Genetics and Genomics at Boston Children's Hospital and co-founder of the N=1 Collaborative, expressed, "This is a crucial new milestone in interventional genetics that fills a long-missing piece in the approval and reimbursement processes. It culminates a development that began with the 2021 FDA guidelines on personalized antisense therapies. By effectively doubling modularity, this framework allows developers to utilize data across therapies aimed at different genetic variants without needing to restart the regulatory process for each mutation. It shows a direction towards a 'plug-and-play' type of genetics future, but such a system cannot be built in isolation. Progress in therapies that is truly greater than the sum of its parts will require knowledge sharing via robust data sharing, where each breakthrough fuels the next."

Sarah Glass, Ph.D., Chief Operating Officer of the n-Lorem Foundation, added, "We have built a robust and scalable process aimed at providing patients with extremely rare diseases individualized ASO-based drugs. We have discovered and developed over 25 ASOs, enabling treatment for more than 45 patients with extremely rare diseases to date. Many of these new ASO-based drugs can potentially be used to treat more patients, and we are committed to getting these drugs to them."

The initiative is joined by organizations such as the n-Lorem Foundation, Mila's Miracle Foundation, and the N=1 Collaborative, all of which are currently gathering founding members to launch this collaborative effort. For further information on the initiative, visit c-path.org/programs/one-to-millions or contact [email protected]

C-Path is hosting a webinar titled "Transforming Drug Development for Precision Medicine: A Practical Approach to Evidence Gathering" and invites everyone to register for another upcoming webinar scheduled for April 8 at noon (Eastern Time) on the topic "Scalable Approaches to Risk-Benefit Assessment from the Patient Perspective: Defining Patient-Centric Drug Development in Precision Medicine."

About Critical Path Institute

Founded in 2005 as a public-private partnership in response to the FDA's Critical Path Initiative, Critical Path Institute (C-Path) is an independent non-profit organization. Its mission is to lead collaboration that contributes to the development of better therapeutics for people around the world. Globally recognized as a pioneer in accelerating drug development, C-Path has established numerous international consortia, programs, and initiatives that currently involve over 1,600 scientists and representatives from government and regulatory agencies, academia, patient organizations, disease-specific foundations, and pharmaceutical and biotechnology companies. C-Path has dedicated team members worldwide, with its global headquarters in Tucson, Arizona, and its European office located in Amsterdam, the Netherlands. For more information, visit c-path.org.