FDA Removes REMS Requirements for Embryofetal Toxicity Risk from All Endothelin Receptor Antagonist Medicines

The US Food and Drug Administration (FDA) announced the removal of Risk Evaluation and Mitigation Strategy (REMS) requirements related to embryofetal toxicity (EFT) risk for all endothelin receptor antagonist (ERA) medicines. This decision was based on a new analysis of two decades of human pregnancy data, through which the FDA concluded that labeling alone is sufficient to effectively communicate these risks to healthcare professionals and patients. Effective April 2025, the REMS for Letairis^® (ambrisentan – Gilead/generics), Opsumit^® (macitentan – Acetlion/generics), Opsynvi^® (macitentan/tadalafil – Johnson and Johnson Innovative Medicine) and Tryvio^® (aprocitentan – Idorsia Pharmaceuticals) were eliminated. Consequently, healthcare professionals can now prescribe and dispense these medications without enrolling in a REMS and patients also do not need to enroll in a REMS now. Additionally, the FDA has instructed manufacturers to modify REMS for Tracleer^® (bosentan – Johnson and Johnson Innovative Medicine/generics) and Filspari^® (sparsentan – Travere Therapeutics) to remove EFT risk requirements, while maintaining hepatotoxicity risk requirements. The updated prescribing information will continue to inform about EFT risks, contraindications in pregnancy and the necessity for effective contraception and ensuring they are not pregnant prior to starting treatment.

New Titration Dosing Approved for Kisunla

On July 9, 2025, the FDA approved a label update for Kisunla^® (donanemab-azbt – Eli Lilly) with a new titration dosing schedule. Kisunla is an amyloid-targeting therapy indicated for treating early symptomatic Alzheimer’s disease, including mild cognitive impairment and mild dementia stages. The new dosing starts with one 350mg vial for the first intravenous (IV) infusion, gradually increasing to four vials by the fourth dose, administered every four weeks. The updated regimen lowers the risk of amyloid-related imaging abnormalities with edema and effusion (ARIA-E) by 41% at 24 weeks and 35% at 52 weeks compared to the original dosing schedule, without compromising the drug’s amyloid-lowering efficacy.  The original regimen, two 350mg vials of the drug for each of the first three infusions before increasing to four vials from the fourth dose, raised safety concerns that limited broader adoption. Updated prescribing information is here.

Full Approval Granted for Moderna’s Spikevax for High-Risk Children Aged 6 Months to 11 Years

Moderna announced on July 10, 2025, that the FDA granted traditional approval to Spikevax^® [coronavirus disease 2019 (COVID-19) Vaccine, mRNA] for the prevention of COVID-19 in children aged six months through 11 years who are at increased risk for severe disease, marking a transition from Emergency Use Authorization to full approval for this pediatric population. Approval was based on a comprehensive review of safety and efficacy data, including prior clinical trials demonstrating protection against severe disease and hospitalization. Here is the prescribing information.