Comment from ADRO

We support FDA's drug repurposing efforts and recommend the following high-unmet-need conditions as priority areas: • Premenstrual Dysphoric Disorder (PMDD) • Chronic Cough • Ehlers-Danlos Syndrome (EDS) • Postural Orthostatic Tachycardia Syndrome (POTS) POTENTIAL DRUG CANDIDATES: • PMDD - GnRH agonists/antagonists, dutasteride, finasteride, brexanolone, zuranolone, venlafaxine, duloxetine, spironolactone. • Chronic Cough - gabapentin, pregabalin, amitriptyline, baclofen, trazodone. • EDS - celiprolol, beta-blockers, H1/H2 antihistamines, cromolyn, montelukast, losartan, cyclobenzaprine, tizanidine, baclofen. • POTS - methylphenidate, propranolol, metoprolol, midodrine, fludrocortisone, droxidopa, pyridostigmine, venlafaxine, desvenlafaxine. BARRIERS The primary barrier to repurposing is lack of economic incentive. For off-patent drugs, sponsors bear the cost of clinical development while competitors benefit from any resulting label expansion. Additional barriers include insurance denials, prior authorizations, lack of awareness, and clinician liability concerns when prescribing off-label. COST OF CLINICAL TRIALS When a drug goes off-patent and generic manufacturers enter the market, no single sponsor can justify spending millions on studies when the average cost of a Phase 3 clinical trial is $800 million USD. Any new indication added to the label would immediately benefit competitors who did not fund the research or sponsor the clinical trials. INSURANCE DENIALS Payers routinely deny coverage for medications prescribed off-label, placing an immense financial burden on patients or burying clinicians in exhausting prior authorization appeals. EXTEND EXCLUSIVITY AND PROVIDE FINANCIAL INCENTIVES TO SPONSORS FDA and Congress should consider mechanisms that provide additional exclusivity or patent-term incentives for sponsors that generate the evidence necessary to support approval of new indications for previously approved drugs. Three years of exclusivity does not justify the cost of large clinical trials. Leverage real-world evidence (EHRs, claims data) and patient advocacy groups to identify diseases where off-label use is common and approved options are limited.