麻豆传媒

WASHINGTON -- Apraglutide, an investigational long-acting synthetic GLP-2 analog, reduced the need for parenteral support in patients with short bowel syndrome and intestinal failure (SBS-IF), a phase III randomized trial showed.

At 24 weeks, the relative change from baseline in weekly parenteral support volume was -25.5% for patients who received a weekly subcutaneous dose of apraglutide compared with -12.5% for the placebo group (P=0.001), reported Francisca Joly, MD, PhD, of Hôpital Beaujon in Clichy, France, during a presentation at the Digestive Disease Week annual meeting.

Key secondary endpoints were also met, with apraglutide significantly increasing additional days off parenteral support per week (43% vs 27.5% in the placebo group, P=0.040).

In addition, more patients treated with apraglutide were clinical responders, defined as ≥20% parenteral support volume reduction at both weeks 20 and 24, compared with the placebo group (42.7% vs 20.8%, P=0.003).

"We had patients at week 24 who were totally rid of parenteral support," Joly said, a "very good" result.

SBS-IF can be caused by inflammatory bowel disease, vascular disease, and surgery, Joly explained. Treatment focuses on providing "nutrition to compensate for the reduction of intestinal function," she noted, "but it's not a curative treatment. It's a palliative treatment."

The 5-year survival rate is typically about 70%, she said

Approximately 18,000 adults in the U.S., Europe, and Japan have SBS-IF. Joly said this study is the largest ever completed in this patient population. Apraglutide, an analog of GLP-2, an "endogenous endocrine peptide that maintains GI nutrient and fluid absorption," works quickly, with effects appearing in 8 weeks, she added.

For this double-blind study known as STARS, the researchers included 164 patients with SBS-IF (all requiring parenteral support at least 3 days a week; mean 5.9 days a week) from 68 centers in 18 countries. Mean age was 51-52, 40-51% were men, 81-86% were white, and 68-70% were European. Eighty patients had stoma, and 83 had colon-in-continuity.

Of the total study population, 95.1% completed treatment, and most continued in a long-term extension study. Of those who dropped out in the apraglutide group, one withdrew consent, four cited adverse events, and one died.

Patients in the stoma and colon-in-continuity subgroups also had significantly greater relative reductions in weekly parenteral support volume at week 24. Enteral autonomy was achieved by more patients treated with apraglutide compared with placebo in both the stoma & colon-in-continuity subgroups at 24 weeks (6.4% vs 0%, P=0.006).

Treatment-related adverse events occurred in 35.5% and 43.4% of the apraglutide and placebo groups, respectively, and serious treatment-related adverse events occurred in 2.7% and 5.7%, respectively.

The most frequent adverse events across the apraglutide and placebo groups through week 48 were nausea (13.6% vs 11.3%), vascular device infection (12.7% vs 9.4%), headache (12.7% vs 11.3%), abdominal pain (10.9% vs 9.4%), diarrhea (10% vs 9.4%), fatigue (10% vs 5.7%), nasopharyngitis (9.1% vs 3.8%), abdominal distension (8.2% vs 7.5%), and arthralgia (7.3% vs 9.4%).

In a , drug maker Ironwood Pharmaceuticals said it "plans to submit a new drug application and other regulatory filings for apraglutide for use in adult patients with SBS who are dependent on parenteral support."

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