Rare Disease Report

Oral Plasma Kallikrein Inhibitor Significantly Reduces Attacks of Hereditary Angioedema

AUGUST 06, 2018
Rachel Lutz
Hereditary angioedema (HAE) can be treated with a new drug called BCX7353, according to a paper published in The New England Journal of Medicine.

HAE can affect just 1 or 2 individuals in a group of 100,000, the investigators said, and it can even be fatal. HAE patients can be plagued by recurrent episodes of severe swelling of the skin and mucous membranes. Typically, HAE appears on the face and around the lips but does not usually leave lasting marks; it can be serious if the swelling occurs in the throat or tongue and blocks the airway, or milder symptoms last more than a few days, according to the Mayo Clinic.

“HAE is a condition that may be associated with lifelong impairment,” principal investigator Emel Aygören-Pürsün, MD, said in a recent statement. Dr Aygören-Pürsün works at the HAE competence center at University Hospital Frankfurt. “With this fundamentally new development, we may reduce HAE attacks and consistently improve our patients' quality of life.”

A team of investigators from Europe conducted a study to test the safety and efficacy of BCX7375. The international study included 72 patients who participated at 26 facilities across Europe, Canada, and Australia. The patients were asked to complete a quality of life questionnaire at the beginning and the end of the study period. The participants also kept a diary of the frequency, location on the body, and severity of the HAE attacks throughout the study period.

The investigators examined 4 doses of BCX7353: 62.mg, 125 mg, 250 mg and 350 mg once daily. They were specifically interested in the prevention of HAE attacks over a 28-day period and the patients received either BCX7353 or placebo. The investigators also looked at angioedema attacks based on their location on the patients’ bodies and the effect on the patients’ quality of life.

The study authors previously understood that HAE is caused by a deficiency or dysfunction of the C1-inhibitor in most cases. When the C1-inhibitor is deficient, plasma levels of bradykinin—a peptide which increases the permeability of small blood vessels—increases. Bradykinin and another plasma protein called kallikrein are linked. When kallikrein is active, more bradykinin is generated. Therefore, the investigators hypothesized, inhibiting kallikrein should be a prophylactic measure against HAE.

BCX73753 is described in the study’s abstract as “a potent oral small-molecule inhibitor of plasma kallikrein with a pharmacokinetic and pharmacodynamic profile that may help prevent angioedema attacks.”

It was developed with ease of administration in mind. Previously, the only medications available were injections and often they could not be administered to pregnant women or children. Instead, this is an oral capsule.

Patients who received BCX7353 at 125 mg daily or higher had significantly lower rates of confirmed HAE attacks compared with those who received a placebo, the investigators reported. In particular, the 125 mg daily dose group experienced nearly 75% reduction in the frequency of their HAE attacks compared with the placebo group. In that group, more than 40% of the patients had no HAE attacks over the 28-day period.

The investigative team also observed significant improvements to the quality of life scores in the groups that received 125 mg daily and 250 mg daily of BCX7353.

The most common adverse events were mild, associated with the gastrointestinal tract, and were mostly found in the 250 mg and 350 mg daily groups, the investigators wrote.

In the future, more studies will be necessary to validate these findings and to determine the safety and efficacy for long-term administration of BCX7353, the investigators concluded.

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