The winding road of BioCryst Pharmaceuticals’ avoralstat has come to an end. The company announced it has concluded development of the plasma kallikrein inhibitor, which was being studied to treat diabetic macular edema (DME).
Abandoning avoralstat is meant to help focus the company’s pipeline on rare diseases, the biopharma explained in a May 6 earnings release. The company's pipeline includes BCX17725, an investigational KLK5 inhibitor in phase 1 trials for the treatment of a rare, severe autosomal recessive genetic disorder called Netherton syndrome.
Avoralstat began as a treatment for hereditary angioedema (HAE), a rare genetic disorder that causes severe swelling in the skin, limbs, intestines and airway. The drug—which aims to inhibit the plasma kallikrein enzyme and reduce excess bradykinin production—advanced into a now-terminated phase 3 study in 2015. The study didn’t demonstrate efficacy in preventing angioedema attacks compared to placebo, though it did shorten the length of attacks.
After avoralstat’s HAE readout, BioCryst continued to pursue a treatment for the condition. It found success in another kallikrein inhibitor, Orladeyo, which was approved in 2020 to treat children and adults with HAE and generated $148.3 million in revenue for BioCryst in the first quarter of this year, according to the company.Â
Orladeyo has competition in the kallikrein inhibitor space. KalVista Pharmaceuticals' Ekterly was approved last year for patients with HAE and was the featured asset in Chiesi Group's acquisition of the company, which was announced last week.
But BioCryst wasn’t done with avoralstat. In 2023, the company announced the drug would be studied to treat DME, a condition in which fluid leaks from damaged retinal blood vessels into the macula, causing swelling, blurred central vision and potential vision loss. It is prevalent in around 5% of patients with diabetes and is a leading cause of blindness in working-age adults in developed countries.Â
Avoralstat’s phase 1b study in DME patients began in October 2025 and enrolled nine individuals. The goal was to show that the drug could deliver a high enough dose to the retinal vessels so that injections would be less frequent than the current standard of care. The trial is now listed as active but not recruiting.
BioCryst had not responded to Fierce Biotech’s questions about the reasons for ending the avoralstat program at the time of publication.