The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved over 30 new oncology agents and new indications for previously approved agents during the third quarter of 2022. One of the main highlights was multiple approvals of the RET inhibitor selpercatinib (Retevmo®; Eli Lilly). Selpercatinib received accelerated approval in the US for second-line treatment of solid tumors and full approval for non-small cell lung cancer (NSCLC). It also received a change to marketing authorization in EMA, with extension of its medullary thyroid cancer indication to first-line use. Another approval of interest was the accelerated approval by the FDA of trastuzumab deruxtecan (Enhertu®; Daiichi Sankyo, AstraZeneca), now the first drug approved for human epidermal growth factor receptor 2 (HER2)-mutant NSCLC. Trastuzumab deruxtecan also received FDA approval for treatment of unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization-negative) breast cancer.
Additional highlights from the third quarter of 2022 include
- Two Kite Pharma chimeric antigen receptor (CAR) T-cell therapies were approved by the EMA for new indications: axicabtagene ciloleucel (Yescarta®) for treatment of diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBCL) and brexucabtagene autoleucel (Tecartus®) for acute lymphoblastic leukemia (ALL) and mantle cell lymphoma (MCL)
- There were also new indications approved for several other previously approved therapies
- Crizotinib (Xalkori®; Pfizer) by the FDA for unresectable, recurrent/refractory inflammatory myofibroblastic tumor (IMT) that is anaplastic lymphoma kinase (ALK) positive; by the EMA for pediatric anaplastic large cell lymphoma (ALCL) and IMT
- Durvalumab (Imfinzi®; AstraZeneca) for biliary tract cancer
- Niraparib (Zejula®; GlaxoSmithKline) for maintenance treatment of advanced ovarian, fallopian tube, and primary peritoneal cancers
- Pemigatinib (Pemazyre®; Incyte Corporation) for relapsed/refractory myeloid/lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) rearrangement (FDA granted priority review, with breakthrough and orphan designations)
- Zanubrutinib (Brukinsa®; BeiGene Ireland, Ltd) for marginal zone lymphoma by the EMA
- Two new biologics for febrile neutropenia received FDA approval: eflapegrastim-xnst (Rolontis®; Spectrum Pharmaceuticals) and pegfilgrastim-fpgk (Stimufend®; Fresenius Kabi USA)
- There were 2 product indications withdrawn
- The ovarian cancer indication for olaparib (Lynparza®; AstraZeneca), withdrawn in the US by the manufacturer
- The EMA recommended that rucaparib camsylate (Rubraca®; Clovis Oncology) no longer be used for third-line ovarian, fallopian tube, or peritoneal cancers, on the basis of results from the ARIEL4 study; it is still approved for use as maintenance treatment following chemotherapy
- This indication was withdrawn in the US also, in June 2022
- The other indications of these agents were not affected by the withdrawals
- Two products previously under accelerated approval received full approval
- Clofarabine (Clolar®; Genzyme) for treatment of pediatric relapsed/refractory ALL
- Capmatinib (Tabrecta®; Novartis) for NSCLC with mesenchymal epithelial transition mutation
- Sodium thiosulfate (Pedmark®, Fennec Pharmaceuticals), approved by the FDA, is the first and only drug approved to reduce the risk of ototoxicity associated with cisplatin in patients 1 month to 19 years old with localized, nonmetastatic solid tumors
The tables below summarize key Q3 oncology approvals:
FDA Approvals |
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Generic Name |
Brand Name |
Tumor Typea |
MOA |
Manufacturer |
Approval |
Acalabrutinib (tablets) |
Calquence® |
MCL, CLL |
TKI |
AstraZeneca |
8/4/22 |
Bendamustine HCl |
Alkylating agent |
Celerity |
7/14/22 (tentative) |
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Bevacizumab-adcd (biosimilar) |
Vegzelma® |
Colorectal, NSCLC, glioblastoma, RCC, cervical, epithelial ovarian, fallopian tube, peritoneal |
Biosimilar referencing Avastin® (Genentech) |
Celltrion, Inc. |
9/27/22 |
Bortezomib |
Multiple myeloma, MCL |
Proteasome inhibitor |
Maia Pharmaceuticals |
7/27/22 |
|
Capmatinib |
Tabrecta |
NSCLC |
MET-targeted kinase inhibitor |
Novartis |
8/10/22 |
Clofarabine |
Clolar |
Pediatric relapsed/refractory ALL |
Nucleoside metabolic inhibitor |
Genzyme |
7/18/22 |
Crizotinib |
Xalkori |
IMT |
TKI |
Pfizer |
7/14/22 |
Darolutamide |
Nubeqa® |
Prostate cancer |
Androgen receptor inhibitor |
Bayer HealthCare Pharmaceuticals |
8/5/22 |
Durvalumab |
Imfinzi |
Biliary tract cancer |
PD-L1 blocker |
AstraZeneca |
9/2/22 |
Eflapegrastim-xnst (biologic) |
Rolontis |
Febrile neutropenia |
G-CSF |
Spectrum Pharmaceuticals |
9/9/22 |
Fam-trastuzumab deruxtecan-nxki |
Enhertu |
HER2-low breast cancer |
HER2-directed antibody-drug conjugate |
Daiichi Sankyo |
8/5/22 |
Fam-trastuzumab deruxtecan-nxki |
Enhertu |
NSCLC with activating HER2 (ERBB2) mutation |
HER2-directed antibody-drug conjugate |
Daiichi Sankyo |
8/11/22b |
Futibatinib |
Lytgobi® |
Cholangiocarcinoma |
FGFR inhibitor |
Taiho Oncology, Inc. |
9/30/22b |
Paclitaxel (albumin-bound) |
Chemotherapy |
Teva |
7/15/22 (tentative) |
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Pegfilgrastim-fpgk |
Stimufend |
Febrile neutropenia |
G-CSF |
Fresenius Kabi USA |
9/1/22 |
Pemetrexed disodium |
NSCLC, malignant mesothelioma |
Folate analog metabolic inhibitor |
Accord Healthcare |
7/18/22 |
|
Pemigatinib |
Pemazyre |
Myeloid/lymphoid neoplasms with FGFR1 rearrangement |
Small-molecule kinase inhibitor |
Incyte Corporation |
8/26/22 |
Selpercatinib |
Retevmo |
Second-line treatment of locally advanced or metastatic solid tumors |
RET inhibitor |
Eli Lilly and Company |
9/21/22 |
Selpercatinib |
Retevmo |
NSCLC with RET gene fusion |
RET inhibitor |
Eli Lilly and Company |
9/21/22 |
Sodium thiosulfate |
Pedmark |
Cisplatin-related ototoxicity in pediatric patients |
Antidote |
Fennec Pharmaceuticals |
9/20/22 |
EMA Approvals |
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Generic Name |
Brand Name |
Tumor Typea |
MOA |
Manufacturer |
Approval |
Axicabtagene ciloleucel |
Yescarta |
DLBCL and HGBCL |
CAR T-cell therapy |
Kite Pharma EU |
September 2022 |
Brexucabtagene autoleucel |
Tecartus |
ALL |
CAR T-cell therapy |
Kite Pharma EU |
July 2022 |
Brexucabtagene autoleucel |
Tecartus |
MCL |
CAR T-cell therapy |
Kite Pharma EU |
August 2022c |
Crizotinib |
Xalkori |
ALCL or IMT |
Kinase inhibitor |
Pfizer Europe MA EEIG |
September 2022 |
Doxorubicin HCl |
Celdoxome pegylated liposomal |
Breast cancer, ovarian cancer, multiple myeloma, Kaposi sarcoma |
Chemotherapy |
YES Pharma |
July 2022d |
Loncastuximab tesirine |
Zynlonta® |
DLBCL and HGBCL |
Monoclonal antibody-drug conjugate |
ADC Therapeutics |
September 2022c |
Relatlimab-nivolumab |
Opdualag™ |
Advanced melanoma |
I-O: PD-1–blocking and LAG-3–blocking antibodies |
Bristol Myers Squibb Pharma |
July 2022d |
Selpercatinib |
Retsevmo® |
Medullary thyroid cancer |
RET inhibitor |
Eli Lilly Nederland |
July 2022 |
Sorafenib |
Sorafenib Accord (generic) |
Hepatocellular and renal cell carcinoma |
Protein kinase inhibitor |
Accord Healthcare |
September 2022d |
Teclistamab |
Tecvayli® |
Multiple myeloma |
Bispecific antibody (targets BCMA and CD3) |
Janssen-Cilag International |
July 2022c |
Thalidomide |
Thalidomide Lipomed (generic) |
Multiple myeloma |
Hybrid medicine |
Lipomed GmbH |
July 2022 |
Zanubrutinib |
Brukinsa |
Marginal zone lymphoma |
BTK inhibitor |
BeiGene Ireland Ltd |
September 2022d |
aPlease see each product’s prescribing information and summary of product characteristics for full indications and labeling information.bAccelerated approval.cConditional marketing authorization.dPositive opinion.ALCL, anaplastic large cell lymphoma; ALL, acute lymphocytic leukemia; BCMA, B-cell maturation antigen; BTK, Bruton tyrosine kinase; CAR, chimeric antigen receptor; CD3, cluster of differentiation 3; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; ERBB2, erb-b2 receptor tyrosine kinase 2; FDA, US Food and Drug Administration; FGFR, fibroblast growth factor receptor; G-CSF, granulocyte colony-stimulating factor; HER2, human epidermal growth factor receptor 2; HGBCL, high grade B-cell lymphoma; IMT, inflammatory myofibroblastic tumor; I-O, immuno-oncology; LAG-3, lymphocyte activation gene 3; MCL, mantle cell lymphoma; MET, mesenchymal-epithelial transition; MOA, mechanism of action; NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein 1; PD-L1, programmed cell death protein 1 ligand 1; RCC, renal cell carcinoma; RET, rearranged during transfection; TKI, tyrosine kinase inhibitor. |
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Sources:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=reportsSearch.process
