BCX4161 (plasma kallikrein inhibitor)
BCX4161 is being developed as an oral prophylactic treatment for patients suffering from Hereditary Angioedema (HAE). In March 2013, BioCryst initiated a Phase 1 clinical trial to evaluate the safety, pharmacokinetics and phamacodynamics of orally-administered BCX4161 in healthy volunteers. In July 2013, BioCryst announced that its randomized, placebo-controlled, Phase 1 clinical trial of orally-administered BCX4161 in healthy volunteers successfully met all of its objectives. The safety, tolerability, drug exposure and on-target kallikrein inhibition results of this Phase 1 trial strongly supported advancing the development program into a Phase 2a trial in high-attack frequency hereditary angioedema (HAE) patients. The OPuS-1 (Oral ProphylaxiS-1) Phase 2a proof of concept clinical trial enrolled its first subject in November 2013 and on May 27, 2014 BioCryst announced that OPuS-1 met the primary efficacy endpoint, several secondary endpoints and all other objectives established for the trial.
BCX4161 inhibits plasma kallikrein and suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients. In preclinical experiments, BioCryst has confirmed the potency of BCX4161 using human plasma and established a predicted therapeutic window to prevent HAE attacks. The oral bioavailability of BCX4161 in preclinical experiments was sufficient to support its continued development. More information is available at the links below:
- "BCX4161, an Oral Kallikrein Inhibitor: Safety and Pharmacokinetic Results of a Phase 1 Study in Healthy Volunteers," P-138, presented at the 2014 AAAAI Annual Meeting, San Diego, CA.
- "A Simple, Sensitive and Selective Fluorogenic Assay to Monitor Plasma Kallikrein Inhibitory Activity of BCX4161 in Activated Plasma," P-143, presented at the 2014 AAAAI Annual Meeting, San Diego, CA.
- "BCX4161, a small molecule orally bioavailable plasma kallikrein inhibitor for the treatment of hereditary angioedema," presented at the 2013 AAAAI Annual Meeting, San Antonio, TX.
Second Generation plasma kallikrein inhibitors
In December 2013, BioCryst selected two optimized next generation kallikrein inhibitors to advance into preclinical development for the treatment of HAE. Its scientists are moving forward based on evidence of superior bioavailability and selectivity, as well as comparable or better potency compared to BCX4161.
About Hereditary Angioedema (HAE)
HAE is a rare, severely debilitating and potentially fatal genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people. HAE symptoms include recurrent episodes of edema in various body parts including the hands, feet, face, genitalia and airway. In addition, patients often have bouts of excruciating abdominal pain, nausea and vomiting that is caused by swelling in the intestinal wall. Airway swelling is particularly dangerous and can lead to death by asphyxiation. Current treatments include potentially toxic oral anabolic steroids for prophylaxis or medicines that are delivered by injection or infusion to either prevent or treat acute attacks. Daily, oral administration of a safe and efficacious prophylactic drug would revolutionize treatment for patients suffering from this serious condition.
For more information on hereditary angioedema, please visit the following websites: