Breakthrough Therapy and RMAT Designations in Oncology

Breakthrough Therapy and RMAT designations can be powerful accelerators in oncology development, but their value depends on more than eligibility alone. In this episode of The Top Line, Stephanie Butler speaks with Sheila Plant, VP of Regulatory Affairs at Allucent, about how sponsors can evaluate which pathway best aligns with their science, evidence package, and development goals.

Plant explains that while both designations offer similar benefits, they are grounded in different evidentiary expectations. Breakthrough Therapy requires preliminary clinical evidence indicating that a drug may demonstrate substantial improvement over available therapies, while RMAT is available for regenerative medicine therapies and focuses on clinical evidence showing the potential to address unmet medical needs for a serious or life-threatening condition, and may be supported by earlier-stage clinical evidence. She also points to common missteps, including moving too early without a sufficiently robust data package or failing to account for manufacturing readiness.

The discussion underscores why regulatory strategy must be built into development planning from the start. Decisions about clinically meaningful endpoints, patient selection, and Phase I and II trial structure can influence whether a program is positioned to take full advantage of an expedited pathway. Plant also cautions that manufacturing, validation, and analytical readiness must keep pace with accelerated clinical timelines. Once a designation is granted, sponsors gain increased collaboration with the FDA, creating opportunities for more real-time feedback and potentially faster development timelines.

For sponsors pursuing RMAT, Breakthrough Therapy, or both, the central takeaway is clear: expedited designations do not accelerate development in isolation. They create opportunities, but outcomes depend on how effectively sponsors plan for, secure, and leverage them.

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About the Speaker

Dr. Sheila Plant, PhD, MHS, RAC, Vice President, Regulatory Affairs

Dr. Sheila Plant, PhD, MHS, RAC, brings more than 27 years of experience, including over 18 years specializing in regulatory affairs and clinical research. She has led marketing application programs resulting in FDA approvals and has extensive experience developing, authoring, compiling, and submitting regulatory applications, including initial INDs, IND amendments, NDAs, and NDA amendments. Her expertise spans regulatory strategy, marketing authorization submissions, and strategic guidance throughout the clinical development lifecycle. With broad FDA interaction experience, Dr. Plant has supported sponsors through regulatory correspondence and provided strategic review and authorship of regulatory and scientific documents designed to advance regulatory interactions and clinical development programs.

Dr. Plant holds a PhD in Neurobiology from the University of North Carolina at Chapel Hill, with training at the Lineberger Comprehensive Cancer Center, and an MHS in Clinical Research from the Duke University School of Medicine Clinical Research Training Program

FAQs

1 What is Breakthrough Therapy designation? +

Breakthrough Therapy designation is an FDA expedited program for a drug intended to treat a serious condition when preliminary clinical evidence indicates that it may offer a substantial improvement over available therapy on one or more clinically significant endpoints. The designation provides more intensive FDA guidance and support to help streamline the drug’s development and review.

2 What is RMAT designation? +

Regenerative Medicine Advanced Therapy (RMAT) designation is an FDA expedited program specifically for regenerative medicine therapies. These therapies use cells, tissues, or genetic material to repair, replace, regenerate, or modify cells or tissues. To receive the designation, a therapy must be intended to treat, modify, reverse, or cure a serious or life-threatening condition, and preliminary clinical evidence must indicate its potential to address an unmet medical need. RMAT designation also provides increased FDA guidance and support to help streamline development and review.

3 What is the difference between Breakthrough Therapy and RMAT designation? +

Both designations require preliminary clinical evidence, but Breakthrough Therapy generally requires stronger evidence than RMAT. Breakthrough Therapy designation may apply to any drug or biologic intended to treat a serious condition. The evidence, often from Phase I or Phase II, must indicate that the therapy may provide substantial improvement over available therapy on a clinically significant endpoint. RMAT designation is limited to regenerative medicine therapies and may be supported earlier in development by preliminary evidence of therapeutic activity in patients and the potential to address an unmet medical need for a serious or life-threatening condition. Once granted, both designations provide similar opportunities for intensive FDA guidance and collaboration.

4 When should a company apply for Breakthrough Therapy or RMAT designation? +

Companies should start planning for these designations at the pre-IND stage, when decisions about patient selection and clinical endpoints can shape the evidence they will collect. They should submit a designation request once they have sufficient preliminary clinical evidence to meet the criteria for Breakthrough Therapy or RMAT. Planning early also gives teams time to prepare for manufacturing scale-up, process validation, and product quality testing if the clinical program accelerates.

5 What evidence is needed for Breakthrough Therapy or RMAT designation? +

Both designations require preliminary clinical evidence. For Breakthrough Therapy, the evidence must indicate that a drug may provide substantial improvement over available therapy on a clinically significant endpoint. That improvement must be supported by a credible comparison, though a concurrent control arm is not always required. For RMAT, early clinical evidence of therapeutic activity in patients must indicate that a regenerative medicine therapy has the potential to address an unmet medical need for a serious or life-threatening condition; it does not need to demonstrate substantial improvement over available therapy.

6 Do Breakthrough Therapy and RMAT designations speed up drug development? +

They can. Both designations provide intensive FDA guidance and more frequent opportunities to discuss the development program, including study design. To take advantage of that guidance, sponsors need to act on FDA feedback and keep clinical studies, manufacturing, and regulatory work moving together. When those activities are ready to advance, the designations can help sponsors streamline development and shorten the overall timeline.

7 How can a CRO help a biotech company pursue Breakthrough Therapy or RMAT designation? +

A CRO can help assess whether the therapy and its clinical evidence meet the criteria for a designation, advise on the timing of the request, and prepare for discussions with the FDA. It can also help design early studies with appropriate patient populations and clinically meaningful endpoints. If the designation is granted, the CRO can help the biotech company act on FDA feedback and coordinate clinical, regulatory, and manufacturing plans so the program is ready to take advantage of an accelerated timeline. Allucent provides this support through its regulatory strategy and cross-functional development teams.

Watch Our Corporate Video

FDA Breakthrough Therapy and RMAT: Strategic Decisions That Can Accelerate Oncology Development

About the Speaker

Dr. Sheila Plant, PhD, MHS, RAC, Vice President, Regulatory Affairs

FAQs

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