Behind the Scenes of an FDA Type C Meeting: A Case Study in Using Gap Analysis to Align Nonclinical Strategy in a Rare Pediatric Disease

By Tom Hallam, Ph.D., MBA

For small pharma companies navigating the road to US market approval, the right nonclinical regulatory strategy, built with expert consulting and scientific guidance, can mean the difference between efficient progress and costly delays. Among the FDA meeting types, the FDA Type C Meeting offers a uniquely flexible forum for dialogue, covering topics not otherwise addressed in other meeting types (e.g., Type A [stalled development], Type B [milestone], or Type D [rapid input on a focused issue]).

From our experience at Facet Life Sciences, proactive and early communication with the Agency, particularly through Type C meetings, can help sponsors align their R&D activities with the Agency’s expectations and avoid costly delays. As Type C FDA meetings are not considered milestone meetings, they offer a unique opportunity to clarify scientific or regulatory issues that arise at any point during development. This is especially critical in rare pediatric diseases, where patient populations are limited and clinical development faces unique scientific challenges.

In this blog, we describe a real-world case study where Facet supported a small pharma company through a nonclinical FDA Type C meeting for a novel gene therapy targeting a fatal pediatric disease, where no other approved treatments exist. Our team conducted a gap analysis, led the preparation and writing of the FDA Type C meeting materials, and provided expert nonclinical regulatory advice throughout the process.

The Situation

Our client was developing a novel gene therapy targeting a rare pediatric neurodegenerative disorder. Facet helped our client clear the initial IND application and commence a Phase 1 clinical trial in healthy adults.
As the program advanced in the clinic, a critical juncture arose in the nonclinical animal studies. While the company previously conducted a juvenile toxicity study in animals that corresponded to patients 12-18 years of age, there were opportunities to also treat younger pediatric patients (ages 2–12) in future clinical trials. Thus, there were questions about the need for additional nonclinical data to support the enrollment of younger children.

Facet’s nonclinical experts advised the client to seek additional FDA guidance on several key issues concerning nonclinical development, including:

• The need for additional juvenile nonclinical toxicity studies to support the inclusion of patients 2-12 years of age in future trials.
• The need for additional biodistribution and pharmacokinetic data in pediatric-age animal models.
• Whether certain toxicology studies could be waived, given the disease’s severity and patient life expectancy.

Given the novel therapeutic modality, intended patient population, and the risk of investing in potentially unnecessary or misaligned nonclinical studies, Facet advised the sponsor to engage in a Type C meeting with FDA to further clarify expectations for nonclinical safety studies to support future pediatric dosing.

The FDA Type C Meeting Submission and Outcome

Using recommendations from the Nonclinical Gap Analysis conducted by Facet’s American Board of Toxicology certified toxicology experts, Facet worked with the company to prepare and submit a Type C meeting request, along with a detailed meeting background package. This package was carefully prepared to support the Sponsor’s position through structured scientific analysis and persuasive regulatory writing, which summarized:

• The available nonclinical data collected to date;
• The proposed nonclinical studies to support future clinical development;
• Specific questions for FDA input with a rationale for each discussion topic.

FDA granted a Type C Written Response Only (WRO) meeting, a common outcome when in-person or real-time (telcon, videoconference) interaction isn’t deemed necessary by FDA.

Key highlights of the Type C FDA WRO meeting feedback included:

• Since the condition manifests in early infancy, a juvenile animal study was required prior to enrolling younger patients.
• Developmental maturity data on target organs in the proposed animal models combined with biodistribution data in adult animals could be used in lieu of pediatric-specific biodistribution data.
• A waiver for reproductive toxicity studies was likely to be granted, given that the target pediatric population was not expected to survive long enough to achieve reproductive potential.

This clear feedback from FDA provided the Sponsor with definitive nonclinical regulatory direction and validated their novel nonclinical strategy, which was shaped through Facet’s targeted gap analysis.

Impact of the Type C Meeting with FDA: A Clear Path Forward

This case highlights how a proactive gap analysis and FDA Type C meeting helped the Sponsor streamline their program and reduce the risk of delays to the clinic. The broad takeaways include:

• The Sponsor avoided conducting unnecessary studies, saving time and resources.
• FDA was able to align on a customized scientifically-sound nonclinical strategy that was identified as part of Facet’s gap analysis.
• The development plan could be streamlined to include the right studies to support pediatric dosing in an efficient and targeted manner.
• The Agency was supportive of Facet’s innovative approach to drug development, when justified and supported by data.

Get Clarity on Your Type C FDA Meeting?

With Facet’s support, the gap analysis and FDA Type C meeting provided the Sponsor much-needed clarity on FDA’s expectations for nonclinical data in a rare pediatric disease setting. Whether you’re facing a unique nonclinical challenge or exploring an accelerated path for rare diseases, Facet Life Sciences can help you analyze, plan, and execute a nonclinical strategy that gets to and through FDA the first time.

Contact us today to start a conversation.