Novel investigational biologics for the treatment of cancer cachexia.
BACKGROUND
Cancer cachexia is a complex multifactorial syndrome characterized by ongoing, irreversible skeletal muscle loss, leading to progressive functional impairment. Several investigational biologics targeting key inflammatory pathways and/or the myostatin/activin type II receptor pathway are in development.


METHODS
Novel therapies include ALD518, MABp1, IP-1510, OHR/AVR118, bimagrumab and REGN1033 and are discussed. For each investigational therapy, the mechanism of action, preclinical data, cachexia definition, indication and clinical data are discussed.


CONCLUSIONS
A critical look of the study protocols and two key challenges limiting the successful evaluation of these agents include: i) lack of a clinically meaningful cachexia definition; and ii) identification and treatment of cachexia in late stage. We describe our observations and clinical experience in an effort to redirect and promote successful strategies to evaluate these novel investigational biologics.
University of California (UC), San Diego, Skaggs School of Pharmacy & Pharmaceutical Sciences , 9500 Gilman Drive, MC 0714, La Jolla, CA 92093-0714 , USA.
Joseph D
JD
Ma
Sean F
SF
Heavey
Carolyn
C
Revta
Eric J
EJ
Roeland
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use*; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D018482:Muscle, Skeletal / Q000378:metabolism; D055435:Myostatin / Q000378:metabolism; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D035703:Therapies, Investigational / Q000379:methods / Q000639:trends
C546400:ALD518 monoclonal antibody; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; C525911:MSTN protein, human; D055435:Myostatin; D017472:Receptors, Interleukin-1
cachexia; cancer; myostatin; skeletal muscle loss