Oral Treatment Candidate BCX7353 Quickly Eases HAE Attacks, Early Phase 2 Trial Findings Show

The oral treatment candidate BCX7353 eases hereditary angioedema (HAE) attacks, reduces the occurrence of symptoms, and helps decrease the use of rescue medications, according to BioCryst Pharmaceuticals’ early Phase 2 trial results.

The data also showed that the investigational therapy was safe and well-tolerated.

BCX7353 is an oral inhibitor of plasma kallikrein, a precursor of bradykinin. This inflammatory molecule is produced at excessive levels in patients with HAE, leading to angioedema attacks and pain.

By targeting kallikrein, the investigational compound is intended to lower the amount of bradykinin. It is being developed as a liquid for acute treatment of HAE and as a capsule to prevent attacks.

Aiming to determine whether BCX7353 shows clinically meaningful efficacy in the severity of HAE attacks, and to define goals for a future Phase 3 study, BioCryst is conducting the proof-of-concept, double-blind, randomized ZENITH-1 Phase 2 trial (NCT03240133) in locations across Europe.

With ZENITH-1 still recruiting participants (more information here),  the company also intends to assess safety, tolerability, and potential doses of BCX7353.

Adult patients with types 1 or 2 of HAE self-administered blinded treatment for three attacks; two treated with BCX7353 and one with a placebo, in a random sequence.

They were asked to administer the treatment within an hour of symptoms’ onset. They were allowed to use prescribed acute medications but were asked to wait at least four hours after administering the medicine, if possible.

Patients completed study diaries to obtain data on symptoms, attack severity with the Visual Analog Scale (VAS), and use of standard of care medicines prior to and at 1, 2, 3, 4, 8 and 24 hours after dosing.

In the 750 mg BCX7353 study group, 33 patients treated a total of 95 attacks  — 64 with BCX7353, 31 with placebo. The treatment candidate provided lessening of symptoms and attack severity as early as one hour after oral dosing. These benefits were sustained through 24 hours.

Also, treating HAE attacks with BCX7353 enabled a 31.6% reduction in standard of care medications use, compared to placebo. The data also showed that no or mild symptoms were reported in 64.1% of BCX7353-treated attacks, in comparison with 32.3% with placebo.

Treatment with the 750 mg dose was generally safe and well-tolerated, leading to no serious adverse events. The most frequently reported adverse events were nasopharyngitis  — or inflammation of the pharynx and nasal cavities (four in attacks treated with BCX7353, one with placebo), diarrhea and headache (both three events with BCX7353 treatment).

Two patients stopped treatment, one following BCX7353 due to a temporary, localized rash, and the other following placebo due to abdominal pain.

“ZENITH-1 represents a groundbreaking study, as the first clinical trial to demonstrate effective treatment of acute HAE attacks with an oral therapy,” Hilary Longhurst, principal investigator of ZENITH-1, said in a press release. She added that the quick lessening of attack severity and the reduction in rescue medications “suggest that BCX7353 has outstanding potential to offer physicians and patients an urgently needed new oral therapy option.”

According to BioCryst, ZENITH-1 is the first trial of an HAE acute therapy evaluating self-administered treatment at home and enabling treatment to be given quickly after start of symptoms.

“We are thrilled to see such a robust treatment effect with BCX7353 in ZENITH-1, using a modern approach with self-administered therapy,” said William Sheridan, BioCryst’s chief medical officer.

According to BioCryst, results from the 250 mg and 500 mg doses are expected in the first quarter of 2019.

In August 2018, the U.S. Food and Drug Administration granted BCX7353 fast track status for the prevention of HAE attacks. In July, BioCryst published results of the APeX-1 Phase 2 trial (NCT02870972) showing that prophylactic treatment with 125 mg BCX7353 reduced HAE attacks by over 70% compared to placebo. Also, a greater number of patients remained attack-free.

Based on these results, the company launched the APeX-2 Phase 3 trial (NCT03485911) and the long-term APeX-S Phase 2 study (NCT03472040) — to continue assessing the safety and effectiveness of its treatment candidate for HAE. Both trials are underway and recruiting participants. (For more information, click on the trials’ identifiers.)

“These results from ZENITH-1, combined with the results we saw in APeX-1, are evidence that BCX7353 would be the first safe and effective oral drug for both treating and preventing HAE attacks,” commented Jon Stonehouse, BioCryst’s CEO.

“We look forward to completing APeX-2 and to submitting our applications for product approval to regulatory authorities,” he added.