In early December 2021, specialty pharmaceutical company Aytu BioPharma, Inc. (“Aytu”) announced that its therapy AR101 (enzastaurin) earned Orphan Drug designation from the FDA. According to the announcement, the therapy received this status for the treatment of Ehlers-Danlos syndrome (EDS), a rare inherited connective tissue disorder. Although vascular EDS (vEDS) currently has no treatment, vEDS is covered under the Orphan Drug status. Ultimately, this highlights that patients with vEDS could have some burgeoning therapeutic options on the horizon!

AR101

To begin, what exactly is AR101? According to Aytu, AR101 is:

a well characterized PKCβ inhibitor that has been evaluated in over 50 clinical trials, with more than 3300 patients. Recent findings from animal studies, in a vEDS mouse model with similar Col3A1 mutations have shown that the mutation is a key mediator in increased PKC/ERK pathway signaling.

Thus, AR101 has the potential ability to reduce the risk of spontaneous aortic ruptures, as well as other health issues. Moving forward, Aytu hopes to study AR101 within the PREVEnt clinical trial to learn more about its safety, efficacy, and tolerability.

AR101 as an Orphan Drug

Orphan Drug designation is granted by the FDA to drugs or biologics which improve treating, diagnosing, or preventing rare conditions. In this case, rare diseases or conditions are defined as those affecting under 200,000 Americans. Since Aytu received this status, the company also earned a variety of incentives such as fee waivers, tax credits, increased regulatory assistance, and 7 years of market exclusivity upon approval.

Ehlers-Danlos Syndrome (EDS)

Ehlers-Danlos syndrome (EDS) consists of a group of inherited disorders which may manifest in various ways, such as vascular (vEDS) or hyper-mobile (hEDS). Regardless of type, EDS affects connective tissues throughout the body. EDS results from collagen and protein defects; normally, collagen and protein help maintain tissue function and structure.

Symptoms of EDS vary based on subtype. For today, we’re going to focus on vEDS. vEDS is considered the most severe EDS subtype and may manifest in childhood. Symptoms and complications include:

• Fragile tissues that are prone to rupturing
• Thin, translucent, velvet-like skin
• Small joint hypermobility
• Varicose veins
• Pneumothorax (collapsed lung)
• Easy bruising
• Receding gums
• Dental cavities
• Premature skin aging on the hands and feet
• Gastrointestinal infarctions
• Arterial aneurysm