Comment from Tom Slover

I am the father of a child with severe autism. I offer the following comments and requests for action. **ASD Should be a Priority Area** The need for treatments is real and unmet. Per CDC ADDM data (2025), approximately 1 in 31 children aged 8 in the United States had ASD in 2022. Despite the prevalence and decades of research, there are no FDA-approved treatments for the core symptoms of autism. Not one. Yet there are many promising studies that urgently need support. **Repurposing Fits the Biology of ASD** One of the key reasons there are no approved treatments is biology. Autism is not a single biological condition; it is a behavioral diagnosis. Different underlying biologies can result in children who meet the clinical definition of ASD, which is itself a spectrum. It is therefore not surprising that no single therapy works for all of them. That is precisely why repurposing is uniquely well-suited to ASD, and why label expansion is the pragmatic near-term opportunity. Often times, drugs (novel and repurposed) show meaningful benefit for some, but not all, in ASD trials. This is what should be expected when testing a population with a heterogenous etiology against a treatment with a specific mechanism of action. In some cases, the problem may not be that the drug lacks effect, but rather that the effect is being measured against the wrong denominator. This variability creates a genuinely confusing landscape for families and the pediatricians, neurologists, and psychiatrists they turn to: clinicians who may be unfamiliar with the latest ASD-specific research and thus, hesitant to prescribe treatments that could help. Ideally, we could identify individuals likely to respond to a particular treatment in advance based on their biology. Unfortunately, we are not there yet in our biological understanding of ASD. Repurposing helps fill that gap. Allowing formal repurposing would also encourage health insurance companies to cover such treatments, rather than denying treatment on the basis of being "unproven" or "beyond the scope of patients suitable for treatment". Where to look? The academic literature is full of studies showing ASD benefits from approved medications. The list of drugs is so long that researchers have published systematic analyses scoring them by strength of evidence in ASD. **Financial Incentives are Needed - especially in ASD** Clinical trials to demonstrate efficacy in the modern era are very expensive. Autism’s biological heterogeneity, lack of established biomarkers, and requirement of subjective behavioral endpoints only escalate those costs for ASD clinical trials. The need for financial incentives to fund repurposing studies is particularly acute in ASD. And every dollar spent on treating autism and improving symptoms would save many more dollars of expenses relating to special education, housing and caring for people with ASD. I request the following actions be taken: 1. Designate ASD as a priority area for drug repurposing. It meets every criterion this RFI describes. 2. Pursue label expansion for approved drugs with established safety profiles and credible signals of benefit in ASD. This is the step FDA can take now, with existing authority, that would have the most immediate impact. 3. Create financial incentives for sponsors who fund trials or data collection leading to label expansion of approved drugs in priority areas. 4. Finally, while it goes beyond the scope of this RFI, I encourage FDA to take two further steps: provide guidance on what evidence would support approval for a treatment-responsive ASD subgroup, and establish a working group to identify trial designs better suited to ASD's heterogeneity. The same biology that makes repurposing attractive also makes conventional all-comers trials a poor fit for ASD. Thank you for your consideration.