01—Abstract
Summary
Summary of the 8-K filed May 28, 2024. Cited figures are marked; the original filing is the authoritative source.
Insmed Incorporated (INSM) announced positive topline results from its Phase 3 ASPEN study of brensocatib in patients with non-cystic fibrosis bronchiectasis on May 28, 2024.
The study met its primary endpoint: both the 10 mg and 25 mg doses produced statistically significant reductions in the annualized rate of pulmonary exacerbations versus placebo, with reductions of 21.1%a (p=0.0019) and 19.4% (p=0.0046), respectively. Several prespecified secondary endpoints were also statistically significant, including time to first exacerbation, odds of remaining exacerbation free over 52 weeks, and change in FEV1 for the 25 mg dose (38 mL, p=0.0054). Reductions in the annualized rate of severe exacerbations and the 10 mg FEV1 change were not statistically significant.
The company plans to file a New Drug Application with the FDA in the fourth quarter of 2024, and anticipates a U.S. launch in mid-2025, followed by launches in Europe and Japan in the first half of 2026, pending regulatory approvals. Brensocatib has Breakthrough Therapy Designation from the FDA and PRIME access from the European Medicines Agency. If approved, it would be the first treatment for bronchiectasis and the first approved DPP1 inhibitor.
Reported safety was broadly comparable to placebo: any TEAE occurred in 77.7%b (10 mg), 76.7% (25 mg) and 79.6% (placebo) of patients, and TEAEs leading to death were 0.5%, 0.7% and 1.2%, respectively. Hyperkeratosis was more frequent with the 25 mg dose (3.0%) than with placebo (0.7%).
The company is also advancing brensocatib in chronic rhinosinusitis without nasal polyps (Phase 2 underway) and plans a Phase 2 study in hidradenitis suppurativa in the second half of 2024. Detailed ASPEN results are expected at an upcoming medical meeting.
02—Key points
Key Highlights
- Primary endpoint met: annualized rate of pulmonary exacerbations reduced 21.1% (10 mg, p=0.0019) and 19.4% (25 mg, p=0.0046) versus placebo.
- Secondary endpoints significant for both doses: time to first exacerbation (18.7% and 17.5%) and odds of remaining exacerbation free over 52 weeks (41.2% and 40.0%).
- FEV1 improvement of 38 mL at week 52 for the 25 mg dose (p=0.0054); the 10 mg dose (11 mL, p=0.3841) was not significant.
- Reduction in annualized rate of severe exacerbations (25.8% and 26.0%) was not statistically significant (p=0.1277 and p=0.1025).
- Regulatory plans: NDA submission to the FDA in Q4 2024, anticipated U.S. launch in mid-2025, and launches in Europe and Japan in the first half of 2026, pending approval.
- Brensocatib has FDA Breakthrough Therapy Designation and PRIME access from the EMA; if approved, it would be the first bronchiectasis treatment and first approved DPP1 inhibitor.
- Safety comparable to placebo: any TEAE in 77.7% (10 mg), 76.7% (25 mg) and 79.6% (placebo) of patients; hyperkeratosis was higher with 25 mg (3.0%) than placebo (0.7%).
03—Questions
Frequently Asked Questions
Did the ASPEN study meet its primary endpoint?
Yes. Both the 10 mg and 25 mg doses of brensocatib showed statistically significant reductions in the annualized rate of pulmonary exacerbations versus placebo, at 21.1% (p=0.0019) and 19.4% (p=0.0046), respectively.
When does Insmed plan to submit for FDA approval and launch in the U.S.?
Insmed plans to file a New Drug Application with the FDA in the fourth quarter of 2024 and anticipates a U.S. launch in mid-2025, pending regulatory approvals.
Were there any endpoints that did not reach statistical significance?
Yes. The reduction in the annualized rate of severe pulmonary exacerbations (25.8% for 10 mg, p=0.1277; 26.0% for 25 mg, p=0.1025) and the FEV1 change for the 10 mg dose (11 mL, p=0.3841) were not statistically significant. The QoL-B Respiratory Score change was nominally significant only for the 25 mg dose (3.8 points, p=0.0004).
How well was brensocatib tolerated in the ASPEN study?
The company described brensocatib as well-tolerated. Any TEAE occurred in 77.7% (10 mg), 76.7% (25 mg) and 79.6% (placebo) of patients. TEAEs leading to death were 0.5%, 0.7% and 1.2%, respectively, and TEAEs leading to treatment discontinuation were 4.3%, 3.8% and 4.1%. Hyperkeratosis was more common with the 25 mg dose (3.0%) than placebo (0.7%).
What other indications is Insmed pursuing for brensocatib?
A Phase 2 study in chronic rhinosinusitis without nasal polyps is currently underway, and Insmed plans to initiate a Phase 2 study in hidradenitis suppurativa in the second half of 2024.
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