WTAS: FDA Launches Framework for Accelerating Development of Individualized Therapies for Ultra-Rare Diseases

The U.S. Food and Drug Administration on Monday issued draft guidance for sponsors seeking approval for targeted individualized therapies by generating substantial evidence of effectiveness and safety when randomized controlled trials are not feasible due to small patient populations.

The draft guidance, issued by the Center for Biologics Evaluation and Research and Center for Drug Evaluation and Research, specifically discusses genome editing and RNA-based therapies such as antisense oligonucleotides but leaves open the potential that this framework may apply to additional tailored therapeutics provided they directly address the underlying specific cause of the disease.

Headlines
Doctors & Scientists
Government Officials
Advocates & Organizations

Headlines:

• AP: FDA proposes new system for approving customized drugs and therapies for rare diseases
• NPR: The FDA creates a quicker path for gene therapies
• Reuters: US FDA proposes framework to speed rare disease gene therapy approvals
• POLITICO: FDA rolls out new rare-disease drug playbook
• AXIOS: FDA smooths reviews of rare disease treatments
• Bloomberg: FDA Unveils New Framework to Speed Ultra-Rare Drug Approvals
• STAT: FDA unveils rules for bespoke gene therapies, predicting flood of rare disease applications
• The Hill: FDA proposes new treatment approval pathway for ultrarare diseases
• Washington Examiner: FDA moves to facilitate personalized therapies for rare diseases
• BioSpace: FDA’s Bespoke Pathway to Focus on Gene Editing and RNA-Based Treatments for Rare Diseases
• Fierce Biotech: FDA illuminates new approval pathway for bespoke gene editing therapies
• MedPage Today: FDA Proposes New Approval Pathway for Rare Disease Gene Therapy
• Spectrum 1 News: FDA says it will speed up rare disease treatment approvals
• Medical Xpress: FDA proposes new system for approving customized drugs and therapies for rare diseases
• Seeking Alpha: Rare disease pharmas could benefit from FDA guidance to accelerate development
• Becker’s Hospital Review: FDA unveils pathway for ultra-rare disease therapies
• Infection Control Today: FDA Rare Disease Day 2026: Moving Forward With Urgency, Innovation, and Patient Voice

Doctors & Scientists:

• Children’s Hospital of Philadelphia via X: “Drs. Becca Ahrens-Nicklas & Kiran Musunuru joined the @FDA to announce a new “plausible mechanism” framework to speed approvals for rare diseases where large, randomized trials aren’t possible. This was inspired by their work w/ our patient KJ. More: http://ms.spr.ly/6013QkCPR.”
• Fyodor Urnov, professor of molecular therapeutics at UC Berkeley and a Scientific Director at its Innovative Genomics Institute via NPR: “Today's guidance is the best imaginable ‘ready, set, go!’ for the field of personalized gene editing as a therapy…To hear HHS leadership say: ‘a disease with 100 causing mutations will no longer require 100 clinical trials’ sounds like a veritable ‘Ode to Joy’ because it means we will be able to treat children faster and more affordably.”
• Penn Cardiovascular Institute's director of genetic and epigenetic origins of disease program in Philadelphia, Kiran Musunuru, MD, PhD, via MedPage: “My team created a genetic therapy to turn off a cholesterol gene in the liver, permanently reduce cholesterol levels, and give lifelong protection against heart disease…And this therapy is now showing signs of success in clinical trials. The beauty of this kind of therapy is that it has a small component that acts like a GPS -- switch the address in that GPS and the therapy will go to another gene and make a desired change. Otherwise, it's pretty much the same therapy…We'll be continuing our work with the FDA using the plausible mechanism framework that's being published today, with the goal of getting to an approval of this platform as efficiently as possible, and getting individualized treatments for [these types of] disorders to all the patients in the U.S. who could benefit from them…”
• C. Michael Gibson, cardiologist and researcher, via X: “FDA unveils rules for bespoke gene therapies, predicting flood of rare disease applications. “Sponsors should demonstrate that the targeted genetic variant(s) are unique to the patient(s)” being treated.” Sponsors will have to provide a justification for why it is not feasible to run a randomized clinical trial in the target patient population. The pathway would not be limited to rare diseases of a particular size, but could be applied to “any diseases that have a very well defined cellular or molecular mechanism” and “where there is a very targeted, tailored treatment to this specific problem.”
• Rachel Sachs, a law professor at Washington University in St. Louis via NPR: ‘The plausible mechanism policy seems like it's addressing a real problem…”
• Robert Y. Chen, PGY-3 at University of Washington via X: “The @US_FDA announced sweeping guidance on how the US is going to lead rare disease therapeutics in the next decade. Huge shoutout to @DrMakaryFDA on this - really pioneering.”

Government Officials:

• Sen. Roger Marshall via X: “Patients with ultra-rare diseases often face impossible odds. I applaud today’s framework from @SecKennedy and @DrMakaryFDA to cut unnecessary barriers, speeding the path to new therapies and giving families hope.”
• Rep. Diana Harshbarger via Facebook: “As a pharmacist, I’ve seen families desperate for answers when a child is diagnosed with a rare disease. Today I stood with Secretary Kennedy and Dr. Makary as the U.S. Food and Drug Administration announced draft guidance to accelerate individualized therapies for ultra-rare diseases. Nearly 1 in 10 Americans — many of them children — lives with a rare condition. They cannot afford government delay. President Trump’s Right to Try law changed the conversation. Now we build on that momentum — unleashing American innovation, streamlining regulations, and putting patients over paperwork. That’s what Making America Healthy Again looks like.”

Advocates & Organizations:

• Washington Health Innovation Council and JK Strategies founder, Jack Kalavritinos, via LinkedIn: “As founder of the Washington Health Innovation Council and former HHS and FDA official, I applaud the President, Secretary Kennedy, Commissioner Marty Makary M.D., M.P.H. and the team at the FDA for delivering on the promise from both Trump Administrations to break down old ways of thinking and get cures to patients faster. Today is historic, as innovators and researchers in individualized medicine will be able to use this approach for conditions where there is a plausible reason to think that the therapy will act on the underlying genetic or cellular biology of the disease. Kudos to my former HHS colleague and tireless rare disease advocate Judy Stecker who has worked closely with HHS to create this pathway. HHS leadership is green-lighting individualized medicine that uses real world evidence to help the 30 million Americans suffering from debilitating and often fatal rare diseases. Patient advocates, innovators, physicians/researchers and investors should take advantage of the 60-day comment period for the new guidance.”
• Washington Health Innovation Council and JK Strategies founder, Jack Kalavritinos, via X: “Yesterday was truly historic at @HHSGov. Patients are being put first and innovators and researchers are having barriers removed to getting life- changing and life-saving cures to Americans.”
• EveryLife Foundation via X: “On Monday, the @US_FDA released more details about the Plausible Mechanism Framework. The Plausible Mechanism Framework is a set of recommendations to help those developing individualized therapies generate sufficient evidence that they are safe and effective, and that they can be manufactured appropriately. The EveryLife Foundation team will closely review the draft Guidance, alongside the Community Congress Regulatory Working Group in the coming weeks and together, we will continue to press for policy solutions that acknowledge the differences in how rare disease products must be developed and evaluated. Today’s release of the Plausible Mechanism Framework Draft Guidance was a meaningful step in that direction.”
• Wilson Center’s acting chair, David Mansdoerfer, via X: “A long time coming. Excellent work coming out of the FDA and @DrMakaryFDA”
• National Organization for Rare Disorders via press release: “NORD is encouraged by efforts to strengthen and clarify regulatory tools that advance rare disease treatments. For conditions with extremely small patient populations, where traditional clinical trials are difficult to conduct, regulatory flexibility is essential. This draft guidance works within FDA’s existing authorities to support innovation for those with specific genetic conditions, where there are frequently significant unmet needs.”
• Goodwin law practice’s chair of life sciences regulatory and compliance practice, Julie Tibbets, via LinkedIn: “ICYMI, Secretary Kennedy announced at today's #HHS #raredisease event on advancing #innovation & celebrating the release of #FDA's Plausible Mechanism draft guidance that: ‘Innovation without accountability destroys trust. Regulation without flexibility destroys hope. We reject both extremes. We choose innovation and accountability. We choose speed and safety. We choose science and compassion. Together we will accelerate cures, empower physicians, heal patients, fuel innovation, and make America healthy again." FDA is accepting comments for 60 days on its draft guidance…’”
• Alliance for Regenerative Medicine’s spokesman, Stephen Majors, via STAT: “Establishing guidance to ensure we have more individualized treatments is a positive step.”