The US government shutdown has interrupted FDA operations, halting new drug and biologic submissions requiring user fees and delaying regulatory decisions. Recent developments include the FDA’s complete response letter rejecting Cyprium Therapeutics’ CUTX-101 for Menkes disease due to manufacturing deficiencies. Meanwhile, Novartis secured FDA approval for Rhapsido (remibrutinib), the first oral Bruton’s tyrosine kinase inhibitor for chronic spontaneous urticaria. CMS finalized guidance establishing orphan drug protections for Medicare negotiations, impacting drug pricing. These regulatory dynamics underscore a challenging environment within US biomedical oversight.