STAR-0215 shows promise as HAE treatment in new Phase 1 trial data

Early results support 3- or 6-month dosing of therapy targeting kallikrein

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A single subcutaneous or under-the-skin injection of STAR-0215 — an experimental treatment that aims to prevent swelling attacks in people with hereditary angioedema (HAE) — led to a sustained decrease in kallikrein protein activity in healthy adults for close to three months, according to new trial data.

Early data also show that a higher dose worked for more than seven months.

The final results from the first dosed groups in a Phase 1a trial in healthy volunteers showed that doses of STAR-0215 at 300 or 600 mg were able to inhibit kallikrein for 84 days, or nearly three months. In HAE, overactive kallikrein leads to the excessive production of a molecule called bradykinin that drives swelling attacks.

Two new groups of volunteers were added to the trial: One received STAR-0215 at a dose of 1,200 mg, while another was given STAR-0215 intravenously, or into the vein, at 600 mg. Initial data from the 1,200 mg group show sustained reduction of kallikrein through 224 days, or between seven and eight months.

“These new data, including long-term follow-up from the original cohorts and initial data from new, higher dose cohorts, support our vision for STAR-0215 as a first-choice therapy for HAE,” Chris Morabito, MD, chief medical officer at Astria Therapeutics, the treatment’s developer, said in a company press release.

William Lumry, MD, a professor at the University of Texas Health Science Center at Dallas, presented the results in a poster, titled “Support for STAR-0215 Administered Every Three- or Six-Months for Hereditary Angioedema: Phase 1a Results,” at the American College of Allergy, Asthma, and Immunology Annual Scientific Meeting, recently held in Anaheim, California.

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According to Morabito, the findings “confirm our approach to administer STAR-0215 once every three and every six months in future trials.”

“We intend to provide patients the option to choose what works best for their lives with a therapy that has a trusted modality and mechanism,” Morabito said.

STAR-0215 is an antibody that blocks kallikrein to prevent swelling. Its mechanism of action is similar to the approved HAE treatment Takhzyro (lanadelumab), which is marketed by Takeda.

Takhzyro is administered once every two weeks as a subcutaneous injection, with the possibility of monthly dosing if patients remain attack-free. STAR-0215 would allow for a less frequent dosing schedule — a significant need identified by HAE patients in a study conducted by Astria.

The Phase 1a trial (NCT05477160), launched in 2022, enrolled 41 healthy adults with a mean age of 38.8; in all, 46.3% of the participants were women. Among those in the study, 51.2% were African-American individuals while 41.5% were white individuals, according to the poster.

The participants were randomly assigned to receive either a single subcutaneous injection of STAR-0215 — at a dose of 100, 300, or 600 mg, or 1,200 mg — or a placebo and were monitored for 224 days. Another group of participants received a single intravenous delivery of STAR-0215 at a dose of 600 mg or a placebo.

The poster presented the final data from the 100, 300, and 600 mg groups, as well as an interim analysis of the 1,200 mg and intravenous administration groups.

In total, 31 participants received STAR-0215 — 25 by subcutaneous injection and six intravenously — and 10 a placebo.

Treatment with STAR-0215 was well tolerated, with no serious adverse events or discontinuations reported. The most common treatment-related adverse events were injection-site reactions of redness, occurring in 22.6%, and itchy skin and swelling, both seen in 12.9% of cases.

The medication’s pharmacokinetics — its movement into, through, and out of the body — and pharmacodynamics, or its effects on the body, also were assessed.

Complete pharmacokinetics data were available through the 224 days post-injection in all groups, through 112 days for the 1,200 mg subcutaneous dose, and through 84 days for the 600 mg intravenous group.

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The results showed rapid and dose-related increases in STAR-0215 levels. All groups except the lowest dose (100 mg) led to mean concentrations of STAR-0215 above the threshold of 12 micrograms/milliliter that was deemed to have potential clinical benefits.

STAR-0215’s half-life, meaning the time needed for its levels to be reduced by half in the bloodstream, was 127 days, or about 4.2 months.

Relative to the placebo, kallikrein activity was significantly blocked in the three subcutaneous groups with higher doses through at least 84 days. In the highest dose, that inhibition was sustained for 224 days.

Levels linked with clinical benefit were maintained with dosing every three months for one year, and every six months for two years, according to pharmacokinetic modelling.

We now expect to deliver initial proof-of-concept data for STAR-0215 as a long-acting preventative therapy for HAE in [the first quarter of] 2024.

A Phase 1b/2 trial, called ALPHA-STAR (NCT05695248) is now enrolling HAE patients to test the treatment candidate. After a run-in period, participants will receive either a single subcutaneous injection or two injections one or three months apart.

“Our Phase 1b/2 ALPHA-STAR trial in HAE patients is on track and enrolling the third and final cohort,” Morabito said.

“We now expect to deliver initial proof-of-concept data for STAR-0215 as a long-acting preventative therapy for HAE in [the first quarter of] 2024,” Morabito added.

Patients who complete ALPHA-STAR can enroll in a long-term open-label study called ALPHA-SOLAR (NCT06007677), in which they will continue to receive STAR-0215.