دورية أكاديمية
A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema.
| العنوان: | A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema. |
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| المؤلفون: | Petersen RS; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Bordone L; Ionis Pharmaceuticals, Inc., Carlsbad, California, USA., Riedl MA; University of California San Diego, La Jolla, California, USA., Tachdjian R; Department of Pediatrics, University of California, Los Angeles, California, USA.; Providence Saint John's Health Center, Santa Monica, California, USA., Craig TJ; Department of Medicine, Pediatrics, and Biomedical Sciences, Pennsylvania State University, Hershey, Pennsylvania, USA.; Vinmec International Hospital, Times City, Hanoi, Vietnam., Lumry WR; Allergy and Asthma Research Associates Research Center, Dallas, Texas, USA., Manning ME; Medical Research of Arizona, Scottsdale, Arizona, USA., Bernstein JA; Department of Internal Medicine, University of Cincinnati College of Medicine, and Bernstein Clinical Research Center, Cincinnati, Ohio, USA., Raasch J; Midwest Immunology Clinic, Plymouth, Minnesota, USA., Zuraw BL; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of California San Diego, La Jolla, California, USA., Deng Y; Ionis Pharmaceuticals, Inc., Carlsbad, California, USA., Newman KB; Ionis Pharmaceuticals, Inc., Carlsbad, California, USA., Alexander VJ; Ionis Pharmaceuticals, Inc., Carlsbad, California, USA., Lui C; Ionis Pharmaceuticals, Inc., Carlsbad, California, USA., Schneider E; Ionis Pharmaceuticals, Inc., Carlsbad, California, USA., Cohn DM; Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. |
| المصدر: | Allergy [Allergy] 2024 Mar; Vol. 79 (3), pp. 724-734. Date of Electronic Publication: 2023 Nov 27. |
| نوع المنشور: | Clinical Trial, Phase II; Randomized Controlled Trial; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: Denmark NLM ID: 7804028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1398-9995 (Electronic) Linking ISSN: 01054538 NLM ISO Abbreviation: Allergy Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Copenhagen : Wiley-Blackwell Original Publication: Copenhagen, Munksgaard. |
| مواضيع طبية MeSH: | Angioedemas, Hereditary*/drug therapy , Oligonucleotides*, Humans ; Prekallikrein ; Quality of Life ; Treatment Outcome ; Complement C1 Inhibitor Protein/therapeutic use |
| مستخلص: | Background: Hereditary angioedema (HAE) is a potentially fatal disease characterized by unpredictable, recurrent, often disabling swelling attacks. In a randomized phase 2 study, donidalorsen reduced HAE attack frequency and improved patient quality-of-life (ISIS721744-CS2, NCT04030598). We report the 2-year interim analysis of the phase 2 open-label extension (OLE) study (ISIS 721744-CS3, NCT04307381). Methods: In the OLE, the on-treatment study period consisted of fixed (weeks 1-13, donidalorsen 80 mg subcutaneously every 4 weeks [Q4W]) and flexible (weeks 17-105, donidalorsen 80 mg Q4W, 80 mg every 8 weeks [Q8W], or 100 mg Q4W) dosing periods. The primary outcome was incidence and severity of treatment-emergent adverse events (TEAEs). The secondary outcomes included efficacy, pharmacodynamic, and quality-of-life assessments. Results: Seventeen patients continued in the OLE study. No serious TEAEs or TEAEs leading to treatment discontinuation were reported. Mean monthly HAE attack rate was 96% lower than the study run-in baseline rate (mean, 0.06/month; 95% confidence interval [CI], 0.02-0.10; median, 0.04 on-treatment vs. mean, 2.70/month; 95% CI, 1.94-3.46; median, 2.29 at baseline). Mean monthly attack rate for Q8W dosing (n = 8) was 0.29 (range, 0.0-1.7; 95% CI, -0.21 to 0.79; median, 0.00). Mean plasma prekallikrein and D-dimer concentrations decreased, and Angioedema Quality of Life Questionnaire total score improved from baseline to week 105 with donidalorsen. Conclusion: The 2-year interim results of this phase 2 OLE study of donidalorsen in patients with HAE demonstrated no new safety signals; donidalorsen was well tolerated. There was durable efficacy with a 96% reduction in HAE attacks. (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.) |
| References: | Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 guidelines for the management of hereditary angioedema. J Allergy Clin Immunol Pract. 2021;9(1):132-150.e133. Fijen LM, Riedl MA, Bordone L, et al. Inhibition of prekallikrein for hereditary angioedema. N Engl J Med. 2022;386(11):1026-1033. Kenniston JA, Faucette RR, Martik D, et al. Inhibition of plasma kallikrein by a highly specific active site blocking antibody. J Biol Chem. 2014;289(34):23596-23608. Ferrone JD, Bhattacharjee G, Revenko AS, et al. IONIS-PKK(Rx) a novel antisense inhibitor of prekallikrein and bradykinin production. Nucleic Acid Ther. 2019;29(2):82-91. Fields T, Ghebrehiwet B, Kaplan AP. Kinin formation in hereditary angioedema plasma: evidence against kinin derivation from C2 and in support of "spontaneous" formation of bradykinin. J Allergy Clin Immunol. 1983;72(1):54-60. Kaplan AP. Hereditary angioedema: investigational therapies and future research. Allergy Asthma Proc. 2020;41(Suppl 1):S51-s54. Bouillet L, Fain O, Armengol G, et al. Long-term prophylaxis in hereditary angioedema management: current practices in France and unmet needs. Allergy Asthma Proc. 2022;43(5):406-412. Maurer M, Aygören-Pürsün E, Banerji A, et al. Consensus on treatment goals in hereditary angioedema: a global Delphi initiative. J Allergy Clin Immunol. 2021;148(6):1526-1532. Busse P, Kaplan A. Specific targeting of plasma kallikrein for treatment of hereditary angioedema: a revolutionary decade. J Allergy Clin Immunol Pract. 2022;10(3):716-722. Weller K, Groffik A, Magerl M, et al. Development and construct validation of the angioedema quality of life questionnaire. Allergy. 2012;67(10):1289-1298. Weller K, Magerl M, Peveling-Oberhag A, Martus P, Staubach P, Maurer M. The Angioedema Quality of Life Questionnaire (AE-QoL) - assessment of sensitivity to change and minimal clinically important difference. Allergy. 2016;71(8):1203-1209. Christiansen SC, Zuraw BL. Laboratory approaches for assessing contact system activation. Immunol Allergy Clin North Am. 2017;37(3):527-539. Kőhalmi KV, Mező B, Veszeli N, et al. Changes of coagulation parameters during erythema marginatum in patients with hereditary angioedema. Int Immunopharmacol. 2020;81:106293. Defendi F, Charignon D, Ghannam A, et al. Enzymatic assays for the diagnosis of bradykinin-dependent angioedema. PloS One. 2013;8(8):e70140. Prakash TP, Graham MJ, Yu J, et al. Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice. Nucleic Acids Res. 2014;42(13):8796-8807. Crooke ST, Witztum JL, Bennett CF, Baker BF. RNA-targeted therapeutics. Cell Metab. 2018;27(4):714-739. Wang Y, Yu RZ, Henry S, Geary RS. Pharmacokinetics and clinical pharmacology considerations of GalNAc(3)-conjugated antisense oligonucleotides. Expert Opin Drug Metab Toxicol. 2019;15(6):475-485. Baker BF, Xia S, Partridge W, et al. Integrated assessment of phase 2 data on GalNAc(3)-conjugated 2'-O-methoxyethyl-modified antisense oligonucleotides. Nucleic Acid Ther. 2023;33(1):73-80. Craig T, Feuersenger H, Pragst I, Dang J. Prophylactic therapy with subcutaneous C1-inhibitor is associated with sustained symptom control in patients with hereditary angioedema. Allergy Asthma Proc. 2022;43(3):202-208. Banerji A, Riedl MA, Bernstein JA, et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. JAMA. 2018;320(20):2108-2121. Longhurst H, Cicardi M, Craig T, et al. Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor. N Engl J Med. 2017;376(12):1131-1140. Farkas H, Stobiecki M, Peter J, et al. Long-term safety and effectiveness of berotralstat for hereditary angioedema: the open-label APeX-S study. Clin Transl Allergy. 2021;11(4):e12035. Wedner HJ, Aygören-Pürsün E, Bernstein J, et al. Randomized trial of the efficacy and safety of berotralstat (BCX7353) as an oral prophylactic therapy for hereditary angioedema: results of APeX-2 through 48 weeks (part 2). J Allergy Clin Immunol Pract. 2021;9(6):2305-2314.e2304. |
| معلومات مُعتمدة: | Ionis Pharmaceuticals |
| فهرسة مساهمة: | Keywords: AE-QoL; HAE attack; HAE safety; HAE treatment; clinical trial; donidalorsen; hereditary angioedema; ligand-conjugated antisense oligonucleotide; long-term prophylaxis; plasma kallikrein; quality-of-life |
| سلسلة جزيئية: | ClinicalTrials.gov NCT04307381 |
| المشرفين على المادة: | 9055-02-1 (Prekallikrein) 0 (donidalorsen) 0 (Complement C1 Inhibitor Protein) 0 (Oligonucleotides) |
| تواريخ الأحداث: | Date Created: 20231127 Date Completed: 20240301 Latest Revision: 20240710 |
| رمز التحديث: | 20240710 |
| DOI: | 10.1111/all.15948 |
| PMID: | 38009241 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1398-9995 |
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| DOI: | 10.1111/all.15948 |