atacicept

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Ligands
atacicept

GtoPdb Ligand ID: 9517

Synonyms: TACI-Fc | TACI-Ig

Compound class: Peptide or derivative

Comment: Atacicept is a recombinant fusion protein that was designed to inhibit B cells, and which was investigated as an intervention in autoimmune diseases [2]. Mechanistically atacicept neutralises the function of two important B-cell activating factors, BAFF (BLyS) and APRIL. Structurally atacicept contains the BLyS/APRIL-binding extracellular portion of the TACI receptor fused to a modified Fc from human IgG1 [4]. One of the important functions of these two factors in autoimmune disease is their ability to induce proliferation of plasma cells and thus increase Ig production, in particular the production of destructive anti-self antibodies. However, this modality has proven ineffective in autoimmune diseases in clinical studies. As of June 2021 atacicept was being deployed for IgA nephropathy.
Peptide sequences and structural information for this peptide are available from its IMGT/mAb-DB entry. The peptide sequence for atacicept is claimed in patent WO2002094852 [8].

References
1. Baker D, Pryce G, James LK, Schmierer K, Giovannoni G. (2020) Failed B cell survival factor trials support the importance of memory B cells in multiple sclerosis. Eur J Neurol, 27 (2): 221-228. [PMID:31617269]
2. Cogollo E, Cogollo E, Silva MA, Isenberg D. (2015) Profile of atacicept and its potential in the treatment of systemic lupus erythematosus. Drug Des Devel Ther, 9: 1331-9. [PMID:25834391]
3. Gordon C, Wofsy D, Wax S, Li Y, Pena Rossi C, Isenberg D. (2017) Post Hoc Analysis of the Phase II/III APRIL-SLE Study: Association Between Response to Atacicept and Serum Biomarkers Including BLyS and APRIL. Arthritis Rheumatol, 69 (1): 122-130. [PMID:27390168]
4. Isenberg D, Gordon C, Licu D, Copt S, Rossi CP, Wofsy D. (2015) Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial). Ann Rheum Dis, 74 (11): 2006-15. [PMID:24951103]
5. Kappos L, Hartung HP, Freedman MS, Boyko A, Radü EW, Mikol DD, Lamarine M, Hyvert Y, Freudensprung U, Plitz T et al.. (2014) Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol, 13 (4): 353-63. [PMID:24613349]
6. Merrill JT, Wallace DJ, Wax S, Kao A, Fraser PA, Chang P, Isenberg D, ADDRESS II Investigators. (2018) Efficacy and Safety of Atacicept in Patients With Systemic Lupus Erythematosus: Results of a Twenty-Four-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm, Phase IIb Study. Arthritis Rheumatol, 70 (2): 266-276. [PMID:29073347]
7. Morand EF, Isenberg DA, Wallace DJ, Kao AH, Vazquez-Mateo C, Chang P, Pudota K, Aranow C, Merrill JT. (2020) Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study. Rheumatology (Oxford), 59 (10): 2930-2938. [PMID:32107560]
8. Rixon MW, Gross JA. (2002) TACI-immunoglobulin fusion proteins. Patent number: WO2002094852. Assignee: Zymogenetics, Inc.. Priority date: 24/05/2001. Publication date: 10/08/2003.
9. Sergott RC, Bennett JL, Rieckmann P, Montalban X, Mikol D, Freudensprung U, Plitz T, van Beek J, ATON Trial Group. (2015) ATON: results from a Phase II randomized trial of the B-cell-targeting agent atacicept in patients with optic neuritis. J Neurol Sci, 351 (1-2): 174-8. [PMID:25758472]
10. van Vollenhoven RF, Wax S, Li Y, Tak PP. (2015) Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial. Arthritis Rheumatol, 67 (11): 2828-36. [PMID:26137975]

References

1. Baker D, Pryce G, James LK, Schmierer K, Giovannoni G. (2020)
Failed B cell survival factor trials support the importance of memory B cells in multiple sclerosis.
Eur J Neurol, 27 (2): 221-228. [PMID:31617269]

2. Cogollo E, Cogollo E, Silva MA, Isenberg D. (2015)
Profile of atacicept and its potential in the treatment of systemic lupus erythematosus.
Drug Des Devel Ther, 9: 1331-9. [PMID:25834391]

3. Gordon C, Wofsy D, Wax S, Li Y, Pena Rossi C, Isenberg D. (2017)
Post Hoc Analysis of the Phase II/III APRIL-SLE Study: Association Between Response to Atacicept and Serum Biomarkers Including BLyS and APRIL.
Arthritis Rheumatol, 69 (1): 122-130. [PMID:27390168]

4. Isenberg D, Gordon C, Licu D, Copt S, Rossi CP, Wofsy D. (2015)
Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial).
Ann Rheum Dis, 74 (11): 2006-15. [PMID:24951103]

5. Kappos L, Hartung HP, Freedman MS, Boyko A, Radü EW, Mikol DD, Lamarine M, Hyvert Y, Freudensprung U, Plitz T et al.. (2014)
Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial.
Lancet Neurol, 13 (4): 353-63. [PMID:24613349]

6. Merrill JT, Wallace DJ, Wax S, Kao A, Fraser PA, Chang P, Isenberg D, ADDRESS II Investigators. (2018)
Efficacy and Safety of Atacicept in Patients With Systemic Lupus Erythematosus: Results of a Twenty-Four-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm, Phase IIb Study.
Arthritis Rheumatol, 70 (2): 266-276. [PMID:29073347]

7. Morand EF, Isenberg DA, Wallace DJ, Kao AH, Vazquez-Mateo C, Chang P, Pudota K, Aranow C, Merrill JT. (2020)
Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study.
Rheumatology (Oxford), 59 (10): 2930-2938. [PMID:32107560]

8. Rixon MW, Gross JA. (2002)
TACI-immunoglobulin fusion proteins.
Patent number: WO2002094852. Assignee: Zymogenetics, Inc.. Priority date: 24/05/2001. Publication date: 10/08/2003.

9. Sergott RC, Bennett JL, Rieckmann P, Montalban X, Mikol D, Freudensprung U, Plitz T, van Beek J, ATON Trial Group. (2015)
ATON: results from a Phase II randomized trial of the B-cell-targeting agent atacicept in patients with optic neuritis.
J Neurol Sci, 351 (1-2): 174-8. [PMID:25758472]

10. van Vollenhoven RF, Wax S, Li Y, Tak PP. (2015)
Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial.
Arthritis Rheumatol, 67 (11): 2828-36. [PMID:26137975]