The Food and Drug Administration (FDA) has granted Orphan Drug designation to enzastaurin for the treatment of vascular Ehlers-Danlos syndrome (EDS), an inherited connective tissue disorder.

Vascular EDS is the most severe subtype of Ehlers-Danlos syndrome. The disorder is caused by mutation in the COL3A1 gene, which encodes the chains of type III procollagen. Patients with vascular EDS may suffer from life-threatening arterial dissections and ruptures, as well as intestinal and uterine ruptures.

Enzastaurin is an oral first-in-class small molecule serine/threonine kinase inhibitor of the PKC beta, PI3K and AKT pathways; PKC/ERK pathway signaling has been shown to be the driver of vascular EDS based on preclinical models.

The FDA’s Orphan Drug designation is granted to medicines intended to treat or prevent rare diseases or disorders that affect fewer than 200,000 individuals. “Receiving Orphan Drug designation for [enzastaurin] underscores the unmet need for patients with VEDS, for which there are currently no FDA-approved treatments,” said Josh Disbrow, Chief Executive Officer of Aytu BioPharma.

The Company plans to initiate the PREVEnt trial, which will assess the safety and efficacy of enzastaurin in preventing cardiac and arterial events in patients with vascular EDS confirmed with COL3A1 gene mutations, in the first half of 2022.


  1. Aytu BioPharma receives Orphan Drug designation from FDA for AR101 for treatment of vascular Ehlers-Danlos syndrome. News release. December 8, 2021.
  2. Aytu BioPharma announces FDA clearance of Investigational New Drug (IND) application for AR101/enzastaurin in vascular Ehlers-Danlos syndrome. News release. December 13, 2021.