Hematology/oncology
Amtagvi (lifileucel)
Lifileucel is a preparation of autologous tumor-infiltrating lymphocytes (TILs) selected on the basis of antigen specificity and tumor reactivity. Upon reintroduction of lifileucel into the patient, the TILs re-infiltrate the tumor, specifically recognize the tumor-associated antigens (TAAs), and initiate tumor cell lysis. Following lifileucel infusion, Il-2 (aldesleukin) is administered to support TIL expansion in vivo.
Lifileucel is indicated for unresectable or metastatic melanoma in adults previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. It is the first autologous T-cell therapy approved for a solid tumor cancer.
Accelerated approval was based on overall response rate (ORR) and duration of response from results of the C-144-01 clinical trial.
The primary efficacy analysis set included 73 patients from Cohort 4 who received the recommended lifileucel dose. Among the 73 patients, 31.5% achieved an objective response with a median duration of response not reached at 18.6 months follow-up (43.5% of responses had a duration > 12 months). Additionally, the supporting pooled efficacy set included a total of 153 patients from Cohort 4 and Cohort 2. Among the 153 patients, 31.4% achieved an objective response with a median duration of response not reached at 21.5 months follow-up (54.2% of responses had a duration > 12 months). J Immunother Cancer. 2022 Dec;10(12)
The Phase 3 TILVANCE-301 trial is being conducted to confirm clinical benefit.
Tevimbra (tislelizumab)
Tislelizumab is a monoclonal antibody to programmed cell death-1 protein (PD-1). It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Tislelizumab is indicated for unresectable or metastatic esophageal squamous cell carcinoma (ESCC) in patients previously treated with systemic chemotherapy that did not include a PD-L1 inhibitor.
Approval was based on the Phase 3 RATIONALE 302 trial. Median overall survival (OS) in all patients treated with tislelizumab was 8.6 months compared with 6.3 months in the chemotherapy arm (P = 0.0001). In patients with PDL-1 tumor area positivity scores 10% or greater, median OS was 10.3 months with tislelizumab versus 6.8 months with chemotherapy (one-sided P = .0006). J Clin Oncol. 2022 Sep 10;40(26):3065-3076
Vafseo (vadadustat)
Vadadustat is a reversible inhibitor of hypoxia-inducible factor (HIF) prolyl-4-hydroxylases (PH)1, PH2, and PH3. This activity results in the stabilization and nuclear accumulation of HIF-1α and HIF-2α transcription factors, and increased production of erythropoietin (EPO).
It is indicated for treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least 3 months.
FDA approval was supported by the results from the Phase 3 INNO2VATE open-label, noninferiority trials to evaluate the safety and efficacy of vadadustat compared with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD).
In the pooled analysis, 1739 patients received vadadustat and 1732 received darbepoetin alfa. The hazard ratio for major adverse cardiovascular event (MACE) was 1.17, which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24-36 were 0.05 g/dL in the trial involving ESA-untreated patients and -0.01 g/dL in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g/dL. N Engl J Med 2021; 384:1601-1612; N Engl J Med 2021; 384:1589-1600
Voydeya (danicopan)
Danicopan is a first-in-class oral factor D inhibitor indicated for add-on therapy to ravulizumab or eculizumab for extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH).
Danicopan prevents cleavage of complement factor B into the Ba and Bb fragments that are required to form the alternative pathway (AP) complement component C3 convertase (C3bBb), generation of downstream effectors including C3 fragment opsonization, and amplification of the terminal pathway. In PNH, intravascular hemolysis (IVH) is mediated by the terminal membrane attack complex (MAC), while extravascular hemolysis (EVH) is facilitated by C3 fragment opsonization. Danicopan acts proximally in the alternative pathway of the complement cascade to control preferentially C3 fragment–mediated EVH, while coadministered ravulizumab or eculizumab is anticipated to maintain control over MAC-mediated IVH.
Approval was supported by results from the Phase 3 ALPHA trial that compared the addition of danicopan (n = 42) to ravulizumab or eculizumab or the addition of placebo (n = 21). At week 12, the change in hemoglobin from baseline with danicopan plus ravulizumab or eculizumab increased by 2.94 g/dL compared with 0.5 g/dL for placebo (P < 0.0001). Lancet Haematol 2023 Dec;10(12)
Other hematology/oncology approvals
Piqray (alpelisib) – Indication for HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer expanded to include pre and perimenopausal women (previously approved for men and postmenopausal women)
Opdivo (nivolumab) – New indication in combination with cisplatin and gemcitabine for first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma
Brukinsa (zanubrutinib) – Indicated for adults with relapsed or refractory follicular lymphoma (FL) in combination with obinutuzumab after at least 2 lines of systemic therapy
Breyanzi (lisocabtagene maraleucel) – Accelerated approval for treatment of adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor
Iclusig (ponatinib) – Indicated for adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
Besponsa (inotuzumab) – Indication for relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL) expanded to include children aged 1 year and older
Rybrevant (amivantamab) – Approved for first-line treatment of NSCLC with EGFR exon 20 insertion mutations
Onivyde (irinotecan liposomal) – Indicated in combination with oxaliplatin, fluorouracil, and leucovorin for first-line treatment of adults with metastatic pancreatic adenocarcinoma
Tagrisso (osimertinib) – Indicated in combination with pemetrexed and platinum-based chemotherapy as first-line treatment in patients with locally advanced or metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations
Tecvayli (teclistamab) – New biweekly maintenance dosage regimen for patients with multiple myeloma who have achieved and maintained a complete remission
Casgevy (exagamglogene autotemcel) – New indication for transfusion-dependent beta thalassemia in patients aged 12 years and older
Elahere (mirvetuximab soravtansine) – Full approval granted for ovarian cancer
Balversa (erdafitinib) – Indication for urothelial cancer gains full FDA approval (granted accelerated approval initially)
Tepmetko (tepotinib) – FDA grants full approval for non-small cell lung cancer (initially accelerated approval)
Wyost (denosumab) – Biosimilar to Xgeva approved for giant cell tumor or hypercalcemia of malignancy
New indication approved for FIGO 2014 Stage III-IVA cervical cancer in combination with chemoradiotherapy
Full approval granted for hepatocellular carcinoma secondary to hepatitis B (granted accelerated approval initially)
New choline salt dosage form indicated for thrombocytopenia in patients aged 6 years and older with persistent or chronic immune thrombocytopenia (ITP) who experienced insufficient response to corticosteroids, immunoglobulins, or splenectomy
Also indicated for adults to treat thrombocytopenia associated with chronic hepatitis C and adults with severe aplastic anemia
Medscape © 2024 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Mary L. Windle. FDA Drug Approvals Q1 2024 - Medscape - Apr 24, 2024.
Comments