FDA Grants Orphan Drug Designation to DIAG723 for Treatment of HHT

The US Food and Drug Administration (FDA) has granted orphan drug designation to first-in-class antibody DIAG723 for the treatment of hereditary hemorrhagic telangiectasia (HHT).1

Announced by Diagonal Therapeutics on June 18, 2025, DIAG723 also received a positive opinion from the European Medicines Agency (EMA), confirming the medication meets criteria for an orphan drug designation in the European Union.1

HHT is a rare genetic disorder caused by loss-of-function mutations in genes encoding ALK1 (ACVRL1) and endoglin (ENG) receptors, which impair signaling pathways regulating vascular development. This results in the formation of telangiectasias and arteriovenous malformations (AVMs), which are prone to rupture. This causes bleeding events, which can lead to chronic anemia and life-threatening complications.1

DIAG723 is a bispecific antibody targeting key extracellular receptors to restore ALK1 signaling, promoting vascular quiescence. Diagonal Therapeutics has conducted preclinical studies to demonstrate the disease-modifying potential of DIAG723’s mechanism of action, confirming its capacity to restore ALK1 signaling, prevent and reverse AVM formation, and prevent HHT-associated anemia.1

“DIAG723 represents a powerful new approach to treating HHT, supported by a robust preclinical data package that has demonstrated its ability to address the key disease manifestations,” said Alex Lugovskoy, PhD, Chief Executive Officer of Diagonal Therapeutics. “Receiving orphan drug designation from the FDA and a positive opinion from the EMA emphasizes the critical need for effective treatments for HHT and reinforces the potential of DIAG723 to significantly improve the lives of people and families affected by the disease.”1

Diagonal Therapeutics also began a natural history study of adults with HHT on March 4, 2025, with the partnership of the organization Cure HHT. The ongoing study aimed to characterize the variability of patient-reported outcomes, namely epistaxis, hematologic support, and quality of life.2

The study aims to enroll >100 US adults with a confirmed HHT diagnosis. Over a projected 13-month period, participants will record healthcare utilization, hematologic support, daily epistaxis scores, and other periodic patient-reported outcomes. Patients will also participate in regular check-ins with staff.2

“Our ongoing collaboration with Cure HHT has been instrumental in building strong connections with the HHT community, and we express our heartfelt gratitude to the many individuals living with HHT who volunteered to participate in this critical study,” Lugovskoy said. “This study is designed to capture daily changes and adjustments in behavior related to the extensive symptom burden associated with the disease, while informing efficient trial design to accelerate the development of novel treatments.”2

References

1. Diagonal Therapeutics. Diagonal’s First-in-Class Clustering Antibody, DIAG723, Receives Orphan Drug Designation (ODD) from U.S. FDA and an ODD Positive Opinion from EMA for Treatment of Hereditary Hemorrhagic Telangiectasia (HHT). Globe Newswire. June 18, 2025. Accessed June 20, 2025. https://www.globenewswire.com/news-release/2025/06/18/3101304/0/en/Diagonal-s-First-in-Class-Clustering-Antibody-DIAG723-Receives-Orphan-Drug-Designation-ODD-from-U-S-FDA-and-an-ODD-Positive-Opinion-from-EMA-for-Treatment-of-Hereditary-Hemorrhagic.html

2. Diagonal Therapeutics. Diagonal therapeutics Initiates Natural History Study of Adults Living with Hereditary Hemorrhagic Telangiectasia (HHT), a Rare Bleeding Disorder with No Approved Treatments. Globe Newswire. March 4, 2025. Accessed June 20, 2025. https://www.globenewswire.com/news-release/2025/03/04/3036355/0/en/Diagonal-Therapeutics-Initiates-Natural-History-Study-of-Adults-Living-with-Hereditary-Hemorrhagic-Telangiectasia-HHT-a-Rare-Bleeding-Disorder-with-No-Approved-Treatments.html