RECEPTOR-Fc AND LIGAND TRAPS AS HIGH-AFFINITY BIOLOGICAL BLOCKERS: DEVELOPMENT AND CLINICAL APPLICATIONS - Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges - page 142

TABLE 9.1 (Continued)

Generic
Name Fusion Mechanism of Action Approved Indications Exploratory Indications

CTLA4-Ig,
modified (BMS
224818) [78]

Belatacept Inhibition of the CD28-

CD80/86-mediated
co-stimulatory signal
required for T-cell
activation

(Undergoing FDA approval
process)

ACVR2A-Fc
(ActRIIA-IgG1;
ACE-011)

Sotatercept Inhibition of activin A

(proposed) [79,80];
may also inhibit other
BMP family ligands
[81,79]

None Phase I safety, tolerability and

pharmacodynamics study in healthy
postmenopausal women (NCT00709540)
[82]; Phase II for correction of anemia in
endstage renal disease (NCT01146574,
and Phase II/III for chemotherapy induced
anemia (NCT01284348) [83]; Phase II for
solid tumors (NCT01190644); Phase II
for osteolytic lesions of multiple myeloma
(NCT00747123)

ACVR2B-Fc
(ActRIIB.hFc;
ACE-031) [84]

Inhibition of activin A,
myostatin, and GDF11
signaling [85]

None Phase I for muscular atrophy

(NCT00952887); Phase I for muscle loss
(NCT00755638); Phase II for Duchenne
muscular dystrophy (NCT01239758,
suspended based on safety data;
NCT01099761 terminated)

ACVRL1-Fc
(Alk1-IgG1;
ACE-041)

Inhibition of BMP9,
BMP10 [86,87]

None Phase I for advanced solid tumors and

multiple myeloma (NCT00996957)

LTBR-Ig (BG9924)
[88]

Baminercept Inhibition of LTa 1 b 2 [89]

and LIGHT [90]
signaling

None Phase I for chronic HCV hepatitis C

(NCT01164384)

TACI-Ig Atacicept Inhibition of BLyS and

APRIL

None Phase I for multiple myeloma or active

Waldenstrom's macroglobulinemia [91,92];
Phase I for relapsed and refractory B-cell
Non-Hodgkin's lymphoma [93]; Phase
II/III for systemic lupus erythematosus
(NCT00624338) [94]

gp130-Fc, modified
(CR5/18) [95]

Inhibition of
“transignaling” via
soluble IL-6R [96]

None Preclinical [97,98]; no active trials listed

IL-17RA-IgG1 or
IL-17RA-Fc

- Inhibition of IL-17A

[99-101]

None Rheumatoid arthritis, multiple sclerosis,

psoriasis [102,103]; no active trials listed

IL-17RC-Fc Inhibition of IL-17A,

IL-17F, and IL-17A/F
[101,104]

None Rheumatoid arthritis, multiple sclerosis,

psoriasis [102,103]; no active trials listed

BR3-Fc Briobacept Inhibition of BLyS

[105,106]

None Completed phase I in rheumatoid arthritis

[107]; no active trials listed

CD4-IgG2
(PRO-542) [51]

Prevents attachment of
HIV to CD4 [51]

Completed Phase I (NCT00000876) [108]
and Phase II (NCT00055185) for HIV
infections; no active trials listed

Fc-OPG [109] Inhibition of RANKL

[110,111]

None Clinical development for bone loss-

associated conditions [109,112,113]
halted because of superior results and
reduced safety concerns with denosumab
[114,115]

The fusion protein is indicated using the name under which it has appeared in the literature. Where more than one name has been used, HUGO-standardized
nomenclature has been adopted and the names appearing in the literature have been listed in parentheses. Generic names are provided where applicable. The
exploratory indications listed are for the most part those still under development; however, indications no longer being pursued are listed in those cases where
they illuminate the history of development of the drug.