Immune-Oncology Molecules In Development & Articles on Topic in @pharmaceuticalintelligence.com
Curators: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN
UPDATED on 9/5/2017
FDA has approved the world’s first CAR-T therapy, Novartis for Kymriah (tisagenlecleucel) and Gilead’s $12 billion buy of Kite Pharma, no approved drug and Canakinumab for Lung Cancer (may be?)
Curator: Aviva Lev-Ari, PhD, RN
Novartis’ Kymriah (tisagenlecleucel), FDA approved genetically engineered immune cells, would charge $475,000 per patient, will use Programs that Payers will pay only for Responding Patients
Curator: Aviva Lev-Ari, PhD, RN
UPDATED on 9/27/2016
Kite Pharma ($KITE) climbs after Phase II data tee up FDA filing for CAR-T
Kite Pharma ($KITE) has posted an interim analysis of Phase II CAR-T data it thinks are strong enough to support regulatory approval. The CAR-T triggered complete remissions in 47% of patients with an aggressive form of non-Hodgkin lymphoma (NHL), although a dropoff in the number of responders over the first three months has raised questions about durability.
At the time of the interim analysis, Kite had administered its CD19-targeting CAR-T to 51 patients with chemorefractory diffuse large B-cell lymphoma (DLBCL). More than three quarters of patients experienced an objective response. Close to half experienced complete remission. When paired to stronger data from a small group of patients with transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL), Kite thinks the interim analysis boosts its prospects.
UPDATED on 9/27/2016
Amgen Announces Top-Line Results From Phase 3 KYPROLIS® (Carfilzomib) CLARION Study In Newly Diagnosed Multiple Myeloma Patients
Amgen to Hold Analyst Call Today at 8:30 a.m. ET
THOUSAND OAKS, Calif., Sept. 27, 2016 /PRNewswire/ — Amgen (NASDAQ:AMGN) today announced top-line results of the Phase 3 CLARION trial, which evaluated an investigational regimen of KYPROLIS® (carfilzomib), melphalan and prednisone (KMP) versus Velcade® (bortezomib), melphalan and prednisone (VMP) for 54 weeks in patients with newly diagnosed multiple myeloma who were ineligible for hematopoietic stem-cell transplant. The trial did not meet the primary endpoint of superiority in progression-free survival (PFS) (median PFS 22.3 months for KMP versus 22.1 months for VMP, HR = 0.91, 95 percent CI, 0.75 – 1.10). While the data for overall survival, a secondary endpoint, are not yet mature, the observed hazard ratio (KMP versus VMP) was 1.21 (95 percent CI, 0.90 – 1.64). Neither result was statistically significant.
Overall, the adverse events in the KMP arm were consistent with the known safety profile of KYPROLIS. The incidence of Grade 3 or higher adverse events was 74.7 percent in the KMP arm and 76.2 percent in the VMP arm. Fatal treatment-emergent adverse events occurred in 6.5 percent of KMP patients and 4.3 percent of VMP patients. The incidence of Grade 2 or higher peripheral neuropathy, a secondary endpoint, was 2.5 percent in the KMP arm and 35.1 percent in the VMP arm.
UPDATED on 6/8/2016
Cancer researchers see promise in giving patients combinations of multiple drugs that are proving more effective than one or two. But the strategy poses a dilemma for health insurers and patients: even higher prices.
Combination Drug Therapies for Cancer Show Promise at Higher Potential Cost
‘Group discounts’ suggested as one means of cutting cost of medicines in a combination regimen
SOURCE
Immune-Oncology Molecules In Development consist of the following four Classes of Drugs:
- Checkpoint Inhibitors
- PD-1
- PD-L1 (Programmed Death (PD))
- LAG-3
- TIM-3
2. Co-Stimulatory Agents
- CD137/41BB
- OX40
- CD27
- GITR
- CD40
3. Immunomodulators
- CTLA4 (cytotoxic T Lymphocyte Associated protein-4)
- KIR
- IDO IL-2
- IL-21
- CSF1R
- Vaccines
SOURCE: Page 66 in
http://jpmorgan.metameetings.com/confbook/healthcare16/stash/misc/IO%20Combos.pdf
AND
4. 5th generation CAR Signaling
- CAR-T (chimeric antigen receptor T- cell)
T cells are genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs).
PART I:
Immune-Oncology Molecules In Development
Anti-Cancer – Four Drug Classes of Immune-Oncology Molecules in Development, including CAR-T
Curator: Stephen J Williams, PhD
For a bigger version of this table in Word please click on the below file:
Table JPM2016 ImmuneTherapy in Development
Phase inDevelop-ment |
Checkpoint InhibitorsDrug/Pharma |
Co-Stimulatory AgentsDrug/Pharma |
ImmunomodulatorsDrug/Pharma |
5th generation CAR SignalingPharma/PartnersListed asDrug (Target/disease indication) |
Pre-Clinical |
REGN2810/RegeneronPD-1/AgenusAnti-Lag3/Tesaro, AnaptyBioIMP701/Prima BioMedLAG3/Agenus, IncyteLag3/MerckAnti-TIM3/BristolAnti-TIM3/Tesaro, AnaptyBioAnti-TIM3/Agenus |
OX40/AmgenGITR/BristolGITR/PfizerFPA154/Five PrimeAnti-GITR/TG TherapeuticsAnti-GITR/Incyte |
CTLA4/AgenusIDO1/Pfizer,iTEOSF001287/Bristol,FlexusIMA942/RocheVIBR/Pfizer |
Kite Pharma/AmgenMultiple targets/ hematologic & solid tumorsBellicum PharmaBPX-401 (CD19/leukemia)BPX-601 (PSCA/prostate)BPX-701 (PRAME/melanomaCellectis/PfizerCornel/Ohio StateUCART123 (CD123/AML)UCARTCS1 (CD38/multiple myeloma)UCART 38 (CD38 /multiple myeloma)UCART 22 ( CD22/ALL)Juno Therapeutics/CellgeneMUC116 (IL12/ovarian)ROR1 (ROR1/B-ALL)Univ. of Penna/NovartisCAR-T hPSMA (PSMA/prostate) |
Phase I |
BMS986016/Bristol |
Urelumab/ BristolMyersMEDI-0562/ AstraZenecaRG7888/RocheOX40/AgonoxOX40/GSKMK-4166/MerckSEA-CD40/Seattle GeneticsCD40/Roche |
Anti-CEA Il2v/RocheFPA008/Bristol, Five PrimeLY3022855/LillyAMG820/AmgenARRY382/Array, Celgene |
Ziopharm/Intrexon/ MD AndersonCD19 (CD19/B-ALL)Kite Pharma/AmgenKTE-C19 (ZUMA-3/Adult ALL)KTE-C19 (ZUMA-4/pediatric ALL)EGFRvII (EGFR/glioblastoma)Bluebird Bio/Cellgene/Baylorbb2121 (BCMA/B-ALL)Juno Therapeutics/CellgeneJCAR017 (CD19/leukemias)JCAR014 (CD19/NHLymphoma) |
Phase I/II |
MEDI0680/AstraZenec |
PF-05082566/PfizerVarilumab/Celldex, Bristol-Myers |
NKG2A/Innate,AstraZen.dCellVax/BioMatrixAPN301/Apeiron, MerckKGA |
Juno Therapeutics/CellgeneJCAR015 (CD19/ALL)JTCR016 (WT-1/AML,CML) |
Phase II |
Pidlizumab/MedivationAvelumab/Pfizer, MerckKGa |
Lirilumab/BMY/InnateEpacadostat/Incyte, MerckGDC-0919/NewLinkGenetics, RocheTG4010/Transgene S.A.Ontak/Esai, Lilly, TevaDenenicokin/Bristol, NovoNordiskPLX3397/Plexikon, MerckMCS110/NovartisJNJ40346527/JNJT-Vec/AmgenEmactuzumab/Roche |
Univ. of Penna/NovartisCTL019 (CD19/leukemia)Kite Pharma/AmgenKTE-C19 (ZUMA-1/leukemia)KTE-C19 (ZUMA-2/mantle cell leukemia) |
|
Phase III |
Duvalumab/AstraZencaAtezolizumab/Roche |
Tremelimumab/AstraZeneca |
||
Approved |
Opdivo/Bristol-MyersKeytruda/Merck |
Yervoy/Bristol-Myers |
Part II:
Articles on CTLA4 @ pharmaceuticalintelligence.com
Curator: Larry H. Bernstein, MD, FCAP
Combined anti-CTLA4 and anti-PD1 immunotherapy shows promising results against advanced melanoma
Reporter: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
Gene expression and adaptive immune resistance mechanisms in lymphoma
Curator: Larry H Bernstein, MD, FCAP
The Delicate Connection: IDO (Indolamine 2, 3 dehydrogenase) and Cancer Immunology
Author and Curator: Demet Sag, PhD, CRA, GCP
Pancreatic Cancer: Genetics, Genomics and Immunotherapy
Author: Tilda Barliya, PhD
Articles on ‘PD-L1’ @ pharmaceuticalintelligence.com
Curator: Larry H. Bernstein, MD, FCAP
Reporter: Aviva Lev-Ari, PhD, RN
Immuno-Oncology Combination Therapy: Implications For Major Pharma
Reporter: Aviva Lev-Ari, PhD, RN
PD1 Inhibitor atezolizumab may show promise in bladder cancer in patients with high PDL1 expression
Reporter: Stephen J Williams
In Cancer Volume 2 Melanoma
Reporter: Aviva Lev-Ari, PhD, RN
Novel biomarkers for targeting cancer immunotherapy
Curator: Larry H. Bernstein, MD, FCAP
Reporter: Aviva Lev-Ari, PhD, RN
Curator: Aviva Lev-Ari, PhD, RN
Articles on ‘CAR-T’ @ pharmaceuticalintelligence.com
Leaders in the CAR-T Field Are Proceeding With Cautious Hope
Reporter: Stephen J. Williams, Ph.D.
Curator: Larry H. Bernstein, MD, FCAP
In Cancer Volume 2 Steroids, Inflammation, and CAR-T Therapy
In Cancer Volume 2 NIH Considers Guidelines for CAR-T therapy: Report from Recombinant DNA Advisory Committee
Curator & Reporter: Larry H. Bernstein, MD, FCAP
Reporter: Aviva Lev-Ari, PhD, RN
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