Early Trial Supporting 3-month Dosing With STAR-0215 for HAE

Patient trial possible next year into longer-acting preventative treatment

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A single injection of STAR-0215, an experimental treatment to prevent swelling attacks in people with hereditary angioedema (HAE), safely led to rapid and sustained inhibition of the kallikrein protein in healthy adults, according to preliminary data from a Phase 1a trial.

“STAR-0215 has shown early proof of concept for its target profile: of being a long-acting preventative therapy for HAE … and dosing once every 3 months or less frequently,” said Jill C. Milne, PhD, CEO of Astria Therapeutics, the treatment’s developer, said in a company press release.

Kallikrein’s overactivity helps to drive the swelling attacks that mark HAE symptoms. STAR-0215, an antibody, aims to block this protein to prevent swelling episodes and to do so with the less frequent dosing requested by patients. Dosing intervals of up to six months are also being considered for testing.

Astria is planning to launch a proof-of-concept Phase 1b/2 global trial, to be called ALPHA-STAR, evaluating STAR-0215 in HAE patients early next year.

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“These results are an important step forward as we work towards our goal of changing the way that people live with HAE. We’ve heard the desire from the HAE community to normalize their lives, living without limitations from their symptoms and treatments,” Milne said in an emailed statement to Angioedema News.

“Our Phase 1a data support our vision that STAR-0215 can become the new standard of care for HAE attack prevention,” she added.

STAR-0215’s mechanism of action is similar to that of Takeda’s Takhzyro (lanadelumab), an approved HAE preventive treatment.

Takhyzro, however, is given as an under-the-skin injection once every two weeks, lowering to about once a month if patients remain attack free. Astria is developing STAR-0215 to be longer lasting, allowing for a less frequent dosing schedule.

Preclinical data supported this potential, suggesting that STAR-0215 is more potent and has greater stability in the bloodstream than Takhyzro.

Its half-life — the time it takes for the levels of a compound in the bloodstream to drop by half — was more than three times longer than that of Takhyzro in non-human primates, the company reported.

Based on animal and other lab work, scientists predicted that STAR-0215 could remain above minimum therapeutic levels for at least 84 days after a single injection, leading to a more sustained suppression of kallikrein, and therefore, of swelling attacks.

The Phase 1a trial (NCT05477160), which opened in August with regulatory approval, is determining whether that assumption holds in humans, and if treatment would be safe.

A total of 25 healthy adults were randomly assigned to a single under-the-skin injection of STAR-0215 at a dose of 100, 300, or 600 mg, or to a placebo, and are being monitored for 224 days, or between seven and eight months.

Preliminary data, with a cut-off date of Dec. 5, covered those monitored for at least 84 days post-injection, according to an Astria investors report.

STAR-0215 was seen to be well-tolerated at all dose levels up to 84 days, with no serious adverse events. The most common treatment-related side effect was a mild, temporary injection site reaction, usually manifested as skin redness.

The treatment’s pharmacokinetics — its movement into, through, and out of the body — as well as its pharmacodynamics — its engagement with kallikrein in the body — were also assessed. Pharmacokinetic data were available through 84 days post-injection in the 100 mg and 300 mg dosing groups, and through 56 days in the 600 mg dosing group.

Its pharmacokinetic profile in the two highest dose groups supported clinical benefit of up to three months with STAR-0215. Its half-life in the bloodstream is an estimated 110 days, or about 3.5 months — potentially more than five times longer than that of Takhyzro, the company reported.

“Single dose of 300 mg leads to significant durable inhibition of plasma kallikrein observed through 3 months,” the report stated.

A 40% to 60% decrease in the protein’s activity was observed, which is consistent with the levels shown to be able to prevent HAE attacks.

Astria is planning to possibly enroll new groups of healthy adults early next year to test dosing once every six months.

The potential ALPHA-STAR trial will be a treatment safety and tolerability study with secondary goals including the effects of STAR-0215 treatment on HAE attack rates and patients’ quality of life.