Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes

Publication Date:
2018-08-03
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Phagocytes, Granulocytes, and Myelopoiesis, Clinical Trials and Observations
Published by:
http://www.hematology.org/
_version_ 1836399020286672897
autor Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
beschreibung Hypereosinophilic syndromes (HESs) are a heterogeneous group of disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. Whereas most patients respond to glucocorticoid (GC) therapy, high doses are often necessary, and side effects are common. Dexpramipexole (KNS-760704), an orally bioavailable synthetic aminobenzothiazole, showed an excellent safety profile and was coincidentally noted to significantly decrease absolute eosinophil counts (AECs) in a phase 3 trial for amyotrophic lateral sclerosis. This proof-of-concept study was designed to evaluate dexpramipexole (150 mg orally twice daily) as a GC-sparing agent in HESs. Dual primary end points were (1) the proportion of subjects with ≥50% decrease in the minimum effective GC dose (MED) to maintain AEC 〈1000/μL and control clinical symptoms, and (2) the MED after 12 weeks of dexpramipexole (MEDD) as a percentage of the MED at week 0. Out of 10 subjects, 40% (95% confidence interval [CI], 12%, 74%) achieved a ≥50% reduction in MED, and the MEDD/MED ratio was significantly 〈100% (median, 66%; 95% CI, 6%, 98%; P = .03). All adverse events were self-limited, and none led to drug discontinuation. Affected tissue biopsy samples in 2 subjects showed normalization of pathology and depletion of eosinophils on dexpramipexole. Bone marrow biopsy samples after 12 weeks of dexpramipexole showed selective absence of mature eosinophils in responders. Dexpramipexole appears promising as a GC-sparing agent without apparent toxicity in a subset of subjects with GC-responsive HESs. Although the exact mechanism of action is unknown, preliminary data suggest that dexpramipexole may affect eosinophil maturation in the bone marrow. This study was registered at www.clinicaltrials.gov as #NCT02101138.
citation_standardnr 6313514
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-08-03
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/132/5/501?rss=1
schlagwort Phagocytes, Granulocytes, and Myelopoiesis, Clinical Trials and Observations
search_space articles
shingle_author_1 Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
shingle_author_2 Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
shingle_author_3 Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
shingle_author_4 Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
shingle_catch_all_1 Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
Phagocytes, Granulocytes, and Myelopoiesis, Clinical Trials and Observations
Hypereosinophilic syndromes (HESs) are a heterogeneous group of disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. Whereas most patients respond to glucocorticoid (GC) therapy, high doses are often necessary, and side effects are common. Dexpramipexole (KNS-760704), an orally bioavailable synthetic aminobenzothiazole, showed an excellent safety profile and was coincidentally noted to significantly decrease absolute eosinophil counts (AECs) in a phase 3 trial for amyotrophic lateral sclerosis. This proof-of-concept study was designed to evaluate dexpramipexole (150 mg orally twice daily) as a GC-sparing agent in HESs. Dual primary end points were (1) the proportion of subjects with ≥50% decrease in the minimum effective GC dose (MED) to maintain AEC <1000/μL and control clinical symptoms, and (2) the MED after 12 weeks of dexpramipexole (MEDD) as a percentage of the MED at week 0. Out of 10 subjects, 40% (95% confidence interval [CI], 12%, 74%) achieved a ≥50% reduction in MED, and the MEDD/MED ratio was significantly <100% (median, 66%; 95% CI, 6%, 98%; P = .03). All adverse events were self-limited, and none led to drug discontinuation. Affected tissue biopsy samples in 2 subjects showed normalization of pathology and depletion of eosinophils on dexpramipexole. Bone marrow biopsy samples after 12 weeks of dexpramipexole showed selective absence of mature eosinophils in responders. Dexpramipexole appears promising as a GC-sparing agent without apparent toxicity in a subset of subjects with GC-responsive HESs. Although the exact mechanism of action is unknown, preliminary data suggest that dexpramipexole may affect eosinophil maturation in the bone marrow. This study was registered at www.clinicaltrials.gov as #NCT02101138.
Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
Phagocytes, Granulocytes, and Myelopoiesis, Clinical Trials and Observations
Hypereosinophilic syndromes (HESs) are a heterogeneous group of disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. Whereas most patients respond to glucocorticoid (GC) therapy, high doses are often necessary, and side effects are common. Dexpramipexole (KNS-760704), an orally bioavailable synthetic aminobenzothiazole, showed an excellent safety profile and was coincidentally noted to significantly decrease absolute eosinophil counts (AECs) in a phase 3 trial for amyotrophic lateral sclerosis. This proof-of-concept study was designed to evaluate dexpramipexole (150 mg orally twice daily) as a GC-sparing agent in HESs. Dual primary end points were (1) the proportion of subjects with ≥50% decrease in the minimum effective GC dose (MED) to maintain AEC <1000/μL and control clinical symptoms, and (2) the MED after 12 weeks of dexpramipexole (MEDD) as a percentage of the MED at week 0. Out of 10 subjects, 40% (95% confidence interval [CI], 12%, 74%) achieved a ≥50% reduction in MED, and the MEDD/MED ratio was significantly <100% (median, 66%; 95% CI, 6%, 98%; P = .03). All adverse events were self-limited, and none led to drug discontinuation. Affected tissue biopsy samples in 2 subjects showed normalization of pathology and depletion of eosinophils on dexpramipexole. Bone marrow biopsy samples after 12 weeks of dexpramipexole showed selective absence of mature eosinophils in responders. Dexpramipexole appears promising as a GC-sparing agent without apparent toxicity in a subset of subjects with GC-responsive HESs. Although the exact mechanism of action is unknown, preliminary data suggest that dexpramipexole may affect eosinophil maturation in the bone marrow. This study was registered at www.clinicaltrials.gov as #NCT02101138.
Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
Phagocytes, Granulocytes, and Myelopoiesis, Clinical Trials and Observations
Hypereosinophilic syndromes (HESs) are a heterogeneous group of disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. Whereas most patients respond to glucocorticoid (GC) therapy, high doses are often necessary, and side effects are common. Dexpramipexole (KNS-760704), an orally bioavailable synthetic aminobenzothiazole, showed an excellent safety profile and was coincidentally noted to significantly decrease absolute eosinophil counts (AECs) in a phase 3 trial for amyotrophic lateral sclerosis. This proof-of-concept study was designed to evaluate dexpramipexole (150 mg orally twice daily) as a GC-sparing agent in HESs. Dual primary end points were (1) the proportion of subjects with ≥50% decrease in the minimum effective GC dose (MED) to maintain AEC <1000/μL and control clinical symptoms, and (2) the MED after 12 weeks of dexpramipexole (MEDD) as a percentage of the MED at week 0. Out of 10 subjects, 40% (95% confidence interval [CI], 12%, 74%) achieved a ≥50% reduction in MED, and the MEDD/MED ratio was significantly <100% (median, 66%; 95% CI, 6%, 98%; P = .03). All adverse events were self-limited, and none led to drug discontinuation. Affected tissue biopsy samples in 2 subjects showed normalization of pathology and depletion of eosinophils on dexpramipexole. Bone marrow biopsy samples after 12 weeks of dexpramipexole showed selective absence of mature eosinophils in responders. Dexpramipexole appears promising as a GC-sparing agent without apparent toxicity in a subset of subjects with GC-responsive HESs. Although the exact mechanism of action is unknown, preliminary data suggest that dexpramipexole may affect eosinophil maturation in the bone marrow. This study was registered at www.clinicaltrials.gov as #NCT02101138.
Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
Phagocytes, Granulocytes, and Myelopoiesis, Clinical Trials and Observations
Hypereosinophilic syndromes (HESs) are a heterogeneous group of disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. Whereas most patients respond to glucocorticoid (GC) therapy, high doses are often necessary, and side effects are common. Dexpramipexole (KNS-760704), an orally bioavailable synthetic aminobenzothiazole, showed an excellent safety profile and was coincidentally noted to significantly decrease absolute eosinophil counts (AECs) in a phase 3 trial for amyotrophic lateral sclerosis. This proof-of-concept study was designed to evaluate dexpramipexole (150 mg orally twice daily) as a GC-sparing agent in HESs. Dual primary end points were (1) the proportion of subjects with ≥50% decrease in the minimum effective GC dose (MED) to maintain AEC <1000/μL and control clinical symptoms, and (2) the MED after 12 weeks of dexpramipexole (MEDD) as a percentage of the MED at week 0. Out of 10 subjects, 40% (95% confidence interval [CI], 12%, 74%) achieved a ≥50% reduction in MED, and the MEDD/MED ratio was significantly <100% (median, 66%; 95% CI, 6%, 98%; P = .03). All adverse events were self-limited, and none led to drug discontinuation. Affected tissue biopsy samples in 2 subjects showed normalization of pathology and depletion of eosinophils on dexpramipexole. Bone marrow biopsy samples after 12 weeks of dexpramipexole showed selective absence of mature eosinophils in responders. Dexpramipexole appears promising as a GC-sparing agent without apparent toxicity in a subset of subjects with GC-responsive HESs. Although the exact mechanism of action is unknown, preliminary data suggest that dexpramipexole may affect eosinophil maturation in the bone marrow. This study was registered at www.clinicaltrials.gov as #NCT02101138.
Panch, S. R., Bozik, M. E., Brown, T., Makiya, M., Prussin, C., Archibald, D. G., Hebrank, G. T., Sullivan, M., Sun, X., Wetzler, L., Ware, J., Fay, M. P., Dunbar, C. E., Dworetzky, S. I., Khoury, P., Maric, I., Klion, A. D.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
shingle_title_2 Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
shingle_title_3 Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
shingle_title_4 Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
timestamp 2025-06-30T23:36:19.830Z
titel Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
titel_suche Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes
topic W
WW-YZ
uid ipn_articles_6313514