| FDA–Approved Agents |
Doxil®
(doxorubicin HCl liposome injection) |
Ortho Biotech |
Reformulated version of doxorubicin; approved in 2007 for use in combination with Velcade in patients who have not received Velcade and have received at least one prior therapy |
Revlimid®
(lenalidomide) |
Celgene Corporation |
Immunomodulatory agent with multiple effects; approved in June 2006 for use in combination with dexamethasone in patients who have received at least one prior therapy |
Thalomid®
(thalidomide) |
Celgene Corporation |
Immunomodulatory agent with multiple effects; approved in May 2006 for use in combination with dexamethasone as front-line therapy |
Velcade®
(bortezomib for Injection) |
Millennium Pharmaceuticals, Inc. |
Proteasome inhibitor approved in 2005 for use in patients who have received at least one prior therapy |
| Agents in Phase III Study |
Genasense
(Bcl-2 antisense,
G-3139, Augmerosen)
(lenalidomide) |
Genta Incorporated |
Antisense drug |
MRA |
Chugai Pharma USA |
Humanized anti-IL-6 receptor MAb |
| Phase II |
Actimid™
(CC-4047) |
Celgene Corp-
oration |
Type of IMiD™ (immunomodulatory drug) with multiple effects under study in Europe |
Alkylade
(O-6-benzylguanine) |
Keryx |
Chemosensitizing agent that appears to enhance the efficacy of chemotherapy |
Aplidin® |
PharmaMar, SA |
Marine-derived antitumor agent that induces rapid apoptosis |
Atlizumab
(MRA, tocilizumab) |
Chugai
Pharma |
Humanized antibody against the IL-6 receptor. In Phase I studies in the US and Phase II in France. |
AP23573 |
Ariad Pharmaceuticals |
Agent that blocks a critical cell-signaling protein known as mTOR; shrinks tumor cells and inhibits angiogenesis |
Avastin™
(beva-
cizumab) |
Genentech |
Humanized antibody against the VEGF receptor. In Phase I studies in the US and Phase II in France in myeloma. |
Campath-1H
(alemtuzumab) |
Berlex;
Genzyme |
Monoclonal antibody (CD52) being tested in conjunction with allogeneic stem cell transplants to prevent GVHD |
CCI-779
(depsipeptide) |
Wyeth-
Ayerst |
Analog of the antitumor agent rapamycin, for patients who have failed at least one prior therapy |
CC11006 |
Celgene Corporation |
Immunomodulatory drugs with multiple effects |
LED
(PNU-108112; doxorubicin) |
NeoPharm |
Liposome encapsulated doxorubicin |
Mylovenge |
Kirin |
Individualized vaccine therapy using M-protein, a patient specific antigen. |
Panzem™
(2-methoxy-estradiol, 2ME2) |
EntreMed, Inc. |
Angiogenesis inhibitor with multiple effects and orally administered |
PI-88 |
Progen |
Angiogenesis and metastasis inhibitor |
RAD001 |
Novartis |
Inhibits mTOR pathway. |
SU5416
(Semoxind; Semaxanib; SU-5416; TUS-16) |
Pfizer |
A small molecule drug targeting the VEGF-mediated flk-1 tyrosine kinase (TK) pathway; inhibits vascular endothelial growth factor receptor 2 (VEGFr2) activation and blocks angiogenesis. |
Temodar®
(temo-
zolomide) |
Schering
Corp-
oration |
Oral chemotherapy agent |
Treanda™,
(bendamustine
hydrochloride - SDX-105) |
Salmedix |
In clinical use in Germany for multiple myeloma and other cancers; currently undergoing trials in the US for indolent NHL |
Trisenox®
(arsenic
trioxide,
ATO) |
Cephalon |
Anticancer drug with multiple actions |
Vatalanib
PTK-787/ZK222584 |
Novartis |
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor that inhibits cell signaling pathways involved in angiogenesis |
Zactima (ZD6474) |
Astra-Zeneca |
Angiogenesis inhibitor that acts by blocking receptors for VEGF |
Zarnestra™
(R115777, tipifarnib,FTI) |
Johnson and Johnson Pharmaceutical Research and Development |
Farnesyl transferase inhibitor with evidence of target modulation in phase I. |
| Phase I/II |
AMG 162 |
Amgen |
Antibody directed against RANK ligand (RANKL); inhibits bone destruction; given as injection. |
Atiprimod |
Calisto
Pharma-
ceuticals |
Antiinflammatory and antiangiogenic agent that inhibits IL-6 and bone erosion for refractory myeloma in patients who have failed 2 or more therapies. |
Breva-
Rex® |
AltaRex |
Monoclonal antibody directed against the MUC1 protein |
CERA
(Contin-
uous
Erythro-
poiesis
Receptor
Activator) |
Roche |
Novel agent that stimulates red blood cell production for treatment of anemia |
Gallium maltolate |
Titan Pharmaceutical |
Oral form of gallium that displays anti-cancer activity and strengthens bone |
GCS-100 |
GlycoGenesys, Inc |
Carbohydrate-based agent derived from pectin with activity in multiple cancers, and preclinical activity in myeloma |
GCS-100LE |
GlycoGenesys, Inc |
Carbohydrate-based agent derived from pectin with activity in multiple cancers, and preclinical activity in myeloma |
GVAX®
Myeloma
Vaccine |
Cell
Genesys |
Irradiated patient myeloma cell vaccine administered with cells that secrete a cytokine that stimulates immune responses in newly diagnosed patients undergoing transplant |
GX15-070 |
GeminX |
Designed to induce apoptosis (natural cell death) by inhibiting the Bcl-2 family of proteins, one of the most validated and well-studied cancer drug targets. |
HGS-ETR1
(mapatumumab) |
Human Genome Sciences |
Monoclonal antibody directed against a specific TRAIL receptor; promotes apoptosis. |
PX-12 |
ProlX |
Novel chemotherapeutic agent (thioredoxin inhibitor) |
Quadramet®
(EDTMP; Samarium-153 ethylene diamine tetramethylene phosphonate/Samarium) |
Cytogen |
Targeted radionuclide being investigated in combination with melphalan as a conditioning agent for transplant and in combination with Velcade in patients with relapsed or refractory myeloma. |
Sodium Stibogluconate |
VioQuest |
Humanized monoclonal antibody that targets the CD40 antigen. |
SU6668
(SU-6668; SU006668; TSU-68) |
Pfizer |
A synthesized inhibitor of receptor tyrosine kinases (RTK) present in receptors for various growth factors involved in tumor angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet derived growth factor (PDGF); inhibits angiogenesis. |
TACI-IG |
Serono |
A soluble fusion protein that links the extravcellular portion of the transmembrane activator and CAML-interactor (TACI) receptor to the Fc portion of the human immunoglobulin (Ig). |
| Phase I |
1D09C3 |
GPC Biotech,
AG |
Monoclonal antibody that causes apoptosis (programmed cell death) of certain types of cancer cells |
17-AAG
(KOS-953;
geldana-mycin) |
Kosan
Biosciences
Inc. |
Inhibitor of a heat shock protein (Hsp90), which promotes myeloma cell growth and survival |
Allomune System |
BioTransplant |
Enhances BMT effectiveness. |
Alvocidib
(Flavopiridol; NSC 649890; L86-8275; HMR-1275; HMR 1275) |
NCI; Sanofi Aventis |
Semisynthetic analog of rohitukine isolated from the bark of the Indian Dysoxylum binectariferum tree; a potent CDK1 inhibitor that arrests cell cycle progression in either G1 or G2. |
Apo2L-TRAIL
(PRO 1762; PRO1762; TRAIL/Apo2L; Apo2L/TRAIL; AMG 951) |
Genentech |
Soluble form of TRAIL (tumor necrosis factor [TNF]–related apoptosis-inducing ligand), a marker found on the surface of various immune cells that plays a role in tumor cell killing; triggers apoptosis of drug-resistant myeloma cell lines and patient cells. |
Atlizumab
(MRA,
tocilizumab) |
Chugai
Pharma |
Humanized antibody against the IL-6 receptor. In Phase I studies in the US and Phase II in France. |
AVN944
(VX 944) |
Avalon |
2nd generation noncompetitive inosine monophosphate dehydrogenase (IMPDH) inhibitor. |
B-B4-DMI |
Immunogen |
TAP (tumor activated prodrug) monoclonal antibody coupled to a cancer drug targeted against the CD138 protein found on myeloma cells. |
BCX-1777
(furodosine) |
BioCryst
Pharma-
ceuticals |
Drug effective in killing myeloma cells in the lab |
CHIR 258 |
Chiron |
Oral agent that inhibits receptors in the fibroblast growth factor (FGF) pathway, as well as VEGF and platelet-derived growth factor (PDGF) |
CP-571, 871
IGF-1R mAB |
Pfizer |
IGF-1 (monoclonal antibody to insulin-like growth factor-1 receptor) under investigation for relapsed/refractory multiple myeloma |
EM-164 |
Sanofi-Aventis |
Antibody that inhibits insulin-like growth factor (IGF-1), a factor that mediates growth and survival of myeloma cells |
ENMD-0995 |
EntreMed,
Inc./
Celgene |
Derivative of Thalidomide analog (S-3APG) |
huN901-DM1 |
Immunogen |
Monoclonal antibody bound to an anticancer drug directed against the CD56 marker found on myeloma cells coupled with a cancer drug. |
IPI-504 |
Infinity |
Targeted cancer therapy that preferentially induces the death of cancer cells through inhibition of the Hsp-90 complex. |
KOS-1022
(alvespimycin HCl; 17-DMAG; NSC707545)
|
Kosan Biosciences Inc. |
Second generation Heat Shock Protein (HSP) 90 inhibitor |
KOS-953
(tanespimycin; 17-AAG; geldana-mycin)
|
Kosan
Biosciences Inc. |
Inhibitor of a heat shock protein (HSP90) that promotes myeloma cell growth and survival and growth |
LymphoRad™131
(B Lympho-
cyte
Stimulator,
BLyS™) |
Human
Genome
Sciences |
Radiolabeled agent that targets myeloma cells for poor risk patients |
KRX-0401
(Perifosine; D-21266) |
Keryx |
In pre-clinical models and early clinical trials, Perifosine displayed impressive anti-tumor activity, as well as anti-Akt activity. |
MS-275 |
Berlex
Labs |
Histone deacetylase inhibitor that inhibits tumor cell growth |
MV-NIS |
Mayo Clinic |
Oncolytic measles virus belonging to the Edmonstron vaccine lineage. |
NPI-0052 |
Nereus Pharmaceuticals |
Novel marine derived proteasome inhibitor active against multiple myeloma cells which are resistant to bortezomib. |
Pyroxamide |
Merck |
A small molecule inhibitor of histone deacetylase (HDAC). |
SCIO-469 |
Scios, Inc. |
Protein p38 MAP kinase-inhibitor which appears to target pathways involved in resistance to bortezomib |
SGN40 |
Seattle
Genetics |
Monoclonal antibody directed against CD40 |
Vorinostat (SAHA-suberoylanilide hydroxamic acid) |
Merck |
Histone deacetylase (HDAC) inhibitor with marked activity preclinically in multiple myeloma |
Xcytrin
(motexafin
gadolinium) |
Pharma-
cyclics |
Novel drug that induces apoptosis of myeloma cells in the lab; undergoing trials for relapsed/refractory multiple myeloma |
| Preclinical Agents Under Study in the Laboratory |
Amplimexon
(Imexon) |
AmpliMed
Corp |
Cancer drug with immune stimulating and cytotoxic activity with a unique mechanism of action |
Anti-CD38 MAb |
Crucell |
Human monoclonal antibody. |
Apomine™
(SR-45023A) |
Ilex
Oncology |
HMG-CoA inhibitor |
BIBF-1120
(indolinone) |
Boehringer
Ingleheim
Pharma |
Novel chemotherapy drug (VEGF-R2 (kinase) inhibitor) |
CC007 |
Celgene |
Celgene |
CC11006 |
Celgene |
Imid drug with similar mechanism to thalidomide |
CHIR-12.2
(CD40monoclonal antibody) |
Chiron |
Antibody that targets the CD40 protein |
cKap |
Immune System Therapeutics Ltd. |
Chimeric version of the murine antibody, mKap, that induces apoptosis in all myeloma cell lines shown to express the surface antigen KMA. cKap is highly effective in inducing antigen dependent cellular cytotoxicity. Preclinical trials expected by late 2005. |
Curcumin |
MD Anderson |
Component of the spice turmeric, also found in yellow mustard, that induces apoptosis of myeloma cells |
Danton |
Dendreon |
Monoclonal antibody that targets HLA-DR. |
Defibrotide |
Gentium
SpA
(Italy) |
Novel orally bioavailable oligonucleotide with antimyeloma activity and anticoagulant effects. Entering Phase I clinical trials in Italy |
DHMEQ |
|
Inhibitor of NF–κΒ induces death of myeloma cells |
Dimethylcelecoxib
(DMC) |
University of Southern California |
Halts tumor growth in drug-resistant lines of multiple myeloma cells. |
DOM1112 |
Domantis |
Dual targeting domain antibody that selectively kills multiple myeloma cells via CD138. |
GRN163 |
Geron
Corp. |
Telomerase inhibitors that have been shown in vitro to induce apoptosis and inhibit myeloma cell growth |
GW654652 |
GlaxoSmithKline |
Small molecule tyrosine-kinase inhibitor which inhibits all 3 VEGF receptors with similar potency |
hLL1 |
Immuno-
medics |
Humanized monoclonal antibody directed against the CD74 protein found on B cells and myeloma cells |
Highly purified
hematopoeitic stem
cells (HP-HSCs) |
Cellerant
Technologies |
Cells capable of rescuing patients from high dose chemotherapy |
HuMax-CD38 |
Genmab |
In preclinical studies, HuMax-CD38 was effective in killing primary multiple myeloma tumor cells and a range of tumor cell lines by triggering two immune system killing mechanisms: Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement Dependent Cytotoxicity (CDC). |
ISIS 345794 |
Isis |
Antisense drug that targets Signal Transducer and Activator of Transcription 3 (STAT-3), a protein that regulates cell growth and division |
Immu-110 |
Immuno-
medics |
Consists of a humanized monoclonal antibody directed against the CD74 protein found on B cells and myeloma cells (hLL1) coupled to doxorubicin |
LBH589 |
Novartis |
Histone deacetylase (HDAC) inhibitor; induces apoptosis of cancer cells |
LPAAT
(lysopho-
sphatidic
acid
acyltrans
rerase)
-β inhibitors |
Cell Therapeutics Inc. |
These agents directly induce apoptosis of myeloma |
LY2181308 |
Isis/Lilly |
Antisense drug with demonstrated activity in multiple in vivo models of cancer. |
MOR202 |
MorphoSys
AG |
Fully-human antibody directed against CD38 |
NPI-0052 |
Nereus
Pharmaceuticals |
Novel marine derived proteasome inhibitor active against multiple myeloma cells which are resistant to bortezomib |
OGX-427 |
OncoGenex |
A targeted therapeutic that inhibits expression of heat shock protein 27 (Hsp27). |
PD173074 |
Pfizer |
Inhibitor of fibroblast growth factor receptor–3 (FGFR3) |
PXD101 |
CuraGen and TopoTarget A/S |
Small molecule drug that selectively inhibits histone deacetylase |
RANK-Fc |
|
Recombinant human immunoglobulin fusion protein that inhibits RANKL and so inhibits bone destruction |
SCIO-469 |
Scios |
A small-molecule p38 mitogen-activated protein (MAP) kinase inhibitor under development as a potential oral therapy for inflammatory disorders and as a potential treatment for multiple myeloma. |
SD-208 |
Scios |
Inhibitor of transforming growth factor (TGF) beta-1, a resistance factor in myeloma |
Seleciclib |
Cyclacel |
A small molecule Cyclin Dependent Kinase (CDK) inhibitor that causes cancer cell death by inducing apoptosis in tumor cells, currently in clinical trials to show activity against b-cell hematologic malignancies. |
SF1126 |
Semafore
Pharma-
ceuticals,
Inc |
PI3K inhibitor with effects in critical cell signaling pathways demonstrated in in vivo studies |
SGN-70 |
Seattle Genetics |
A humanized MAb that targets the CD70 antigen. |
SDX-101 |
Salmedix |
Oral COX-2 inhibitor that is toxic to myeloma cells and blocks production of myeloma growth factors in bone marrow; also under investigation in CLL |
TSP-1
(Thrombospondin-1) |
Protein
Sciences
Corp. |
Angiogenesis inhibitor with anti-myeloma activity |
