Pamufetinib (TAS-115) for chronic fibrosing interstitial lung diseases with a progressive phenotype: a double-blind,
Ryo Okuda1, Yasuhiko Nishioka2, Yasuhiro Kondoh3,4
1Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan.
Rationale:
No recommended therapy exists for chronic fibrosing interstitial lung diseases (CF-ILDs) with disease progression despite ongoing treatment with nintedanib or pirfenidone. Pamufetinib (also known as TAS-115) is a novel oral antifibrotic tyrosine kinase inhibitor in development for CF-ILD with a progressive phenotype.
Objective:
We sought to evaluate the dose-response of pamufetinib monotherapy in patients with CF-ILD including idiopathic pulmonary fibrosis (IPF) with a progressive phenotype despite an antifibrotic treatment.
Methods:
In this double-blind, multicenter, active-controlled phase 2b study, patients with CF-ILD with a progressive phenotype (defined as ≥ 5% decline in the annual percent predicted FVC [%FVC] despite treatment with nintedanib or pirfenidone and an %FVC ≥ 50%) were randomized 1:1:1 to pamufetinib 50 mg, 100 mg, or control (nintedanib or pirfenidone) for ≥ 6 weeks. The primary endpoint was the 26-week rate of decline in FVC.
Measurements And Main Results:
Of the 243 patients randomized, approximately 70% had IPF. The 26-week rate of change in FVC was -157.8 mL, -95.9 mL, and -63.6 mL in patients receiving pamufetinib 100 mg, pamufetinib 50 mg, and control, respectively; as such, no clear dose-response relationship was observed. The most frequent adverse event in the pamufetinib groups was rash, which was mostly mild or moderate in severity.
Conclusions:
While the safety profile was acceptable, pamufetinib failed to decelerate FVC decline in patients with CF-ILD with a progressive phenotype who had previously been treated with nintedanib or pirfenidone. No benefits were demonstrated by switching from standard antifibrotic treatment to pamufetinib monotherapy.Clinical trial registered with the Japan Registry of Clinical Trials (https://jrct.mhlw.go.jp/en-top; jRCT2051210050).
Insights
Pamufetinib did not slow lung function decline in patients with progressive chronic fibrosing interstitial lung disease (CF-ILD) despite existing treatments. Switching to pamufetinib monotherapy showed no benefit over standard antifibrotic therapy.
Area of Science:
- Pulmonology
- Pharmacology
- Clinical Trials
Background:
- Chronic fibrosing interstitial lung diseases (CF-ILD) lack effective therapies for progressive cases unresponsive to nintedanib or pirfenidone.
- Pamufetinib (TAS-115) is an investigational oral antifibrotic tyrosine kinase inhibitor for progressive CF-ILD.
Purpose of the Study:
- To assess the dose-response of pamufetinib monotherapy in patients with progressive CF-ILD, including idiopathic pulmonary fibrosis (IPF), who were already treated with antifibrotics.
- To evaluate pamufetinib's efficacy in decelerating forced vital capacity (FVC) decline in this patient population.
Main Methods:
- A double-blind, multicenter, active-controlled Phase 2b study randomized 243 patients with progressive CF-ILD to pamufetinib (50mg or 100mg) or control (nintedanib/pirfenidone) for at least 26 weeks.
- The primary endpoint was the rate of FVC decline over 26 weeks.
Main Results:
- No clear dose-response relationship for pamufetinib was observed.
- The 26-week FVC decline rates were -157.8 mL (100mg pamufetinib), -95.9 mL (50mg pamufetinib), and -63.6 mL (control).
- Rash was the most common adverse event in pamufetinib groups, generally mild to moderate.
Conclusions:
- Pamufetinib did not demonstrate efficacy in slowing FVC decline in patients with progressive CF-ILD previously treated with nintedanib or pirfenidone.
- Switching to pamufetinib monotherapy offered no advantages over continuing standard antifibrotic treatments.
- The safety profile of pamufetinib was deemed acceptable.
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