BIBF 1120 is developed by Boehringer Ingelheim. It is a tyrosine kinase inhibitor targeting multiple tyrosine kinase receptors including platelet-derived growth factor receptors (PDGFR) α and β, vascular endothelial growth factor receptors
(VEGFR) 1, 2, and 3, and fibroblast growth factor receptors (FGFR) 1, 2, and 3.
A recent 12-month, randomized, double-blind, placebo-controlled, phase 2 trial (To Improve Pulmonary Fibrosis with BIBF 1120 [TOMORROW]) with 4 doses (50 mg once a day, 50 mg twice a day, 100 mg twice a day, or 150 mg twice a day) may have some positive effect (N = 428 patients). Although highest dose was associated with significant side effects, 150 mg twice a day was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. Although the differences in primary end point among the study groups were not statistically significant, the benefits observed in the study were indeed clinically relevant.
It is encouraging that the trial was, at least, not another failed IPF trial, compared to others (pirfenidone, systemic glucocorticoids, azathioprine and cyclophosphamide, interferon-γ-1b, phosphodiesterase-5 inhibitors, or endothelin receptor antagonists).
I do hope that phase III trial gives more positive news. Since lower doses did not show much, I would guess that next trial uses highest dose, 150 mg b.i.d.
References:
Richeldi L, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87. PubMed PMID: 21992121.
NEJM link: http://www.nejm.org/doi/full/10.1056/NEJMoa1103690.
Downey GP. Resolving the scar of pulmonary fibrosis. N Engl J Med. 2011 Sep
22;365(12):1140-1. PubMed PMID: 21992127.
NEJM link: http://www.nejm.org/doi/full/10.1056/NEJMe1108558.
(VEGFR) 1, 2, and 3, and fibroblast growth factor receptors (FGFR) 1, 2, and 3.
A recent 12-month, randomized, double-blind, placebo-controlled, phase 2 trial (To Improve Pulmonary Fibrosis with BIBF 1120 [TOMORROW]) with 4 doses (50 mg once a day, 50 mg twice a day, 100 mg twice a day, or 150 mg twice a day) may have some positive effect (N = 428 patients). Although highest dose was associated with significant side effects, 150 mg twice a day was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. Although the differences in primary end point among the study groups were not statistically significant, the benefits observed in the study were indeed clinically relevant.
It is encouraging that the trial was, at least, not another failed IPF trial, compared to others (pirfenidone, systemic glucocorticoids, azathioprine and cyclophosphamide, interferon-γ-1b, phosphodiesterase-5 inhibitors, or endothelin receptor antagonists).
I do hope that phase III trial gives more positive news. Since lower doses did not show much, I would guess that next trial uses highest dose, 150 mg b.i.d.
References:
Richeldi L, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87. PubMed PMID: 21992121.
NEJM link: http://www.nejm.org/doi/full/10.1056/NEJMoa1103690.
Downey GP. Resolving the scar of pulmonary fibrosis. N Engl J Med. 2011 Sep
22;365(12):1140-1. PubMed PMID: 21992127.
NEJM link: http://www.nejm.org/doi/full/10.1056/NEJMe1108558.
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