Broad Scope of Unique Targets and Malignancies for New FDA and EMA Drug Approvals as 2023 Concluded

Broad Scope of Unique Targets and Malignancies for New FDA and EMA Drug Approvals as 2023 Concluded

In the fourth quarter of 2023, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved more than 20 new oncology agents and 16 new indications for previously approved agents. The approvals were for approximately 24 solid tumor types and 8 hematologic malignancies. There were 2 diagnostic agents, 5 biologics, 4 programmed cell death protein 1 inhibitors, and drugs with several other targets approved. One treatment was approved by both the FDA and the EMA: pembrolizumab (Keytruda®; Merck & Co) for treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Additional highlights from the fourth quarter of 2023

  • First FDA approval of a therapy to treat progressing desmoid tumors: nirogacestat (Ogsiveo™; SpringWorks Therapeutics)
  • First FDA approval of a therapy intended to reduce the risk of relapse in pediatric patients with high-risk neuroblastoma: eflornithine (Iwilfin™; USWM)
  • First FDA approval that includes patients with ROS proto-oncogene 1 (ROS1)-positive non-small cell lung cancer (NSCLC) who have previously received a ROS1 tyrosine kinase inhibitor (TKI), in addition to patients who are TKI naive
  • Pembrolizumab (Keytruda; Merck & Co) had 7 new approvals; 5 by the FDA, 1 by the EMA, and 1 by both agencies
    • There was also an update to the gastric or GEJ adenocarcinoma indication for pembrolizumab (Keytruda; Merck & Co) by the FDA that restricts use to patients whose tumors express programmed cell death ligand 1 (PD-L1) (combined positive score ³1) as determined by an FDA-approved test
  • A combination of 2 products that previously received accelerated approval gained full approval by the FDA: enfortumab vedotin (Padcev®; Astellas) and pembrolizumab (Keytruda; Merck & Co), for urothelial carcinoma
  • 1 new supportive care biologic agent was approved by the FDA: efbemalenograstim alfa-vuxw (Ryzneuta®; Evive Biotech), for prevention of chemotherapy-induced neutropenia
  • 4 companion diagnostics were approved by the FDA
    • FoundationOne® companion diagnostic for patients with NSCLC who may be eligible for combination treatment with binimetinib (Mektovi®; Array Biopharma) and encorafenib (Braftovi®; Array Biopharma)
    • FoundationOne companion diagnostic for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who may be eligible for treatment with capivasertib (Truqap™; AstraZeneca)
    • Abbott RealTime IDH1 assay to select patients appropriate for ivosidenib (Tibsovo®; Servier)
    • Agilent PD-L1 IHC 22C3 pharmDx to select patients with gastric or GEJ adenocarcinoma appropriate for treatment with pembrolizumab (Keytruda; Merck & Co)
  • 2 formulations of gadopiclenol, an agent for contrast-enhanced magnetic resonance imaging, received positive opinion by the EMA: Elucirem™(Guerbet) and Vueway™(Bracco Imaging), to detect lesions in the central nervous system and other body regions (eg, breast, liver, prostate)
  • Under its Project Orbis initiative, the FDA collaborated with other health agencies to grant 7 approvals. Since its launch in 2019, there has been continued growth in the number of applications submitted to Project Orbis; EMA announced plans to join the multicountry review consortium as an observer
  • 6 FDA approvals used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application: nivolumab (Opdivo®; Bristol Myers Squibb), eflornithine (Iwilfin
  • Re-examination of adagrasib (Krazati®; Mirati Therapeutics) by the EMA resulted in a conditional marketing authorization
  • Non-renewal of the conditional marketing authorization for belantamab mafodotin (Blenrep; GSK Ireland) in multiple myeloma was confirmed by the EMA

The tables below summarize key Q4 2023 oncology approvals.

FDA and EMA Approvals

Generic Name
Brand Name
Tumor Typea
MOA
Manufacturer
Approval
Pembrolizumabb
Keytruda®
Gastric or GEJ adenocarcinoma
PD-1 inhibitor
Merck & Co
811/16/23 (FDA) and October 2023 (EMA)e

 

FDA Approvals

Generic Name
Brand Name
Tumor Typea
MOA
Manufacturer
Approval
Avelumabb
Bavencio
Merkel cell carcinoma
PD-L1 inhibitor
EMD Serono
9/6/23
Bosutinib monohydrate
Bosulif
Pediatric Ph+ CML
Tyrosine kinase inhibitor
PF Prism CV
9/26/23
Dabrafenib
Tafinlar
Tumor agnostic
B-Raf inhibitor
Novartis
8/31/23
Dostarlimab-gxlyb
Jemperli
dMMR endometrial cancer
PD-1 inhibitor
GlaxoSmithKline
7/31/23
Elranatamab-bcmmb
Elrexfio
Multiple myeloma
Bispecific antibody
Pfizer
8/14/23c
Fosaprepitant
Focinvez
Chemotherapy-induced nausea and vomiting
Antiemetic
Spes Pharmaceuticals
8/22/23
Luspatercept
Reblozyl
Anemia in patients with MDS
Recombinant fusion protein
Bristol Myers Squibb
8/28/23
Melphalan
Hepzato Kit
Uveal melanoma with unresectable hepatic metastases
Alkylating agent
Delcath Systems
8/14/23
Momelotinib
Ojjaara
Myelofibrosis and anemia
JAK1/JAK2 and activin A receptor type 1 inhibitor
GlaxoSmithKline
9/15/23
Motixafortide
Aphexda™
Stem cell mobilization in patients with multiple myeloma
CXCR4 antagonist
BioLineRx
9/8/23
Niraparib-abiraterone acetate
Akeega
Prostate cancer
PARP inhibitor plus abiraterone acetate
Janssen Biotech
8/11/23
Pralsetinib
Gavreto®
NSCLC
RET inhibitor
Genentech
8/20/23
Temozolomide
Temodar
Anaplastic astrocytoma
Alkylating agent
Merck
9/14/23
Therascreen PDGFRA RGQ PCR Kit
Therascreen PDGFRA Kit
GI tumors; companion diagnostic for avapritinib
PDGFRA assay
Qiagen
8/7/23
Trametinib
Mekinist
Tumor agnostic, age 1 and older
MEK inhibitor
Novartis
8/31/23
N/A
FoundationOne CDx
Solid tumors
Tissue-based diagnostic
Foundation Medicine
8/14/23

 

EMA Approvals

Generic Name
Brand Name
Tumor Typea
MOA
Manufacturer
Approval
Brentuximab vedotin
Adcetris
Stage III Hodgkin lymphoma
Antibody-drug conjugate
Takeda Pharmaceutical
September 2023
Crisantaspase
Enrylaze®
ALL and lymphoblastic lymphoma
Recombinant Erwinia asparaginase or crisantaspase
Jazz Pharmaceuticals
July 2023e
Dabrafenib
Finlee®
Glioma
B-Raf inhibitor
Novartis
September 2023e
Decitabine- cedazuridine
Inqovi®
AML
Hypomethylating agent
Otsuka Pharmaceuticals
July 2023
Degarelix acetate (generic)
Degarelix Accord
Prostate cancer
GnRH antagonist
Accord
July 2023
Elacestrant
Orserdu™
ER+, HER2– breast cancer with ESR1 mutation
ER antagonist
Stemline Therapeutics
July 2023e
Epcoritamab
Tepkinly®
DLBCL
Bispecific antibody
AbbVie
July 2023e
Glofitamab
Columvi®
DLBCL
Bispecific antibody
Roche
July 2023d
Melphalan flufenamide
Pepaxti
Multiple myeloma
XPO1 inhibitor
Oncopeptides AB
September 2023
Nivolumab
Opdivo
Melanoma
PD-1 inhibitor
Bristol Myers Squibb
July 2023e
Pembrolizumab
Keytruda
NSCLC (adjuvant therapy)
PD-1 inhibitor
Merck Sharp & Dohme
September 2023
Pembrolizumab
Keytruda
HER2+ gastric or gastroesophageal junction adenocarcinoma
PD-1 inhibitor
Merck Sharp & Dohme
July 2023e
Piflufolastat (18F)
Pylclari
Prostate cancer diagnosis
Diagnostic solution
Curium
July 2023
Sacituzumab govitecan
Trodelvy
HR+, HER2– metastatic breast cancer
Trop-2–directed ADC
Gilead
July 2023
Tislelizumab
Tevimbra
Esophageal squamous cell carcinoma
PD-1 inhibitor
Novartis
July 2023e
Trastuzumab (biosimilar)
Herwenda®
Breast cancer and gastric cancer
Monoclonal antibody
Sandoz GmbH
September 2023e
Trastuzumab deruxtecan
Enhertu
NSCLC with HER2 mutation
Antibody-drug conjugate
Daiichi Sankyo
September 2023
+, positive; –, negative; AKT, protein kinase B; ALL, acute lymphocytic leukemia; BRAF, v-Raf murine sarcoma viral oncogene homolog B; BTK, Bruton tyrosine kinase; CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; EMA, European Medicines Agency; FDA, US Food and Drug Administration; G-CSF, granulocyte colony-stimulating factor; GEJ, gastroesophageal junction; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IDH1, isocitrate dehydrogenase 1; JAK, Janus kinase; KRAS, Kirsten rat sarcoma viral proto-oncogene; MDS, myelodysplastic syndrome; MEK, mitogen-activated ERK kinase; MOA, mechanism of action; NSCLC, non-small cell lung cancer; PARP, poly(ADP-ribose) polymerase; PD-1, programmed cell death protein 1; PD-L1, PD-1 ligand 1; PDGFRA, platelet-derived growth factor receptor alpha; Ph, Philadelphia chromosome; RCC, renal cell carcinoma; ROS1, ROS proto-oncogene 1; SLL, small lymphocytic lymphoma; TKI, tyrosine kinase inhibitor; TRK, tropomyosin receptor kinase; VEGF, vascular endothelial growth factor.
aPlease see each product’s prescribing information and summary of product characteristics for full indications and labeling information.
bBiologic.
cAccelerated approval.
dConditional marketing authorization.
ePositive opinion.

 

Sources:

https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=reportsSearch.process

https://www.ema.europa.eu/en/committees/chmp/chmp-agendas-minutes-highlights

https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications

https://www.raps.org/News-and-Articles/News-Articles/2023/11/FDA-notes-continued-growth”-of-Orbis-collaborative

FDA Approvals

Generic Name
Brand Name
Tumor Typea
MOA
Manufacturer
Approval
Belzutifan
Welireg
RCC
Hypoxia-inducible factor inhibitor
Merck & Co
12/14/23
Bevacizumab-tnjn (biosimilar)
Avzivi®
Colorectal cancer, NSCLC, glioblastoma, RCC, cervical cancer, ovarian cancer, fallopian tube cancer, and primary peritoneal cancer
VEGF inhibitor
Bio-Thera Solutions, Ltd
12/06/23