Novel agents for myelodysplastic syndromes

2021 ◽  
pp. 107815522110379
Author(s):  
Katie Xu ◽  
Elizabeth Hansen
Keyword(s):  
Drug Administration ◽  
Myelodysplastic Syndromes ◽  
Primary Outcome ◽  
Food And Drug Administration ◽  
Review Article ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Safety And Efficacy ◽  
Transfusion Independence ◽  
The Us

Review objective There have been several advances in the field of myelodysplastic syndromes over the past year, yielding two new US Food and Drug Administration drug approvals. The pharmacology, pharmacokinetics, clinical trials, therapeutic use, adverse effects, clinical use controversies, product description, and upcoming trials for myelodysplastic syndromes novel agents luspatercept-aamt and decitabine/cedazuridine are reviewed. Data sources This review article utilized primary information obtained from both the published studies involved in the approval of luspatercept-aamt and decitabine/cedazuridine and package inserts for the respective medications. This review article utilized secondary information obtained from National Comprehensive Cancer Network guidelines using filters and keywords to sustain information relevancy as well as key studies using the keywords, “luspatercept-aamt, myelodysplastic syndromes, decitabine, cedazuridine, hypomethylating agent, ASTX727” from scholarly journal database PubMed. Data summary Myelodysplastic syndromes consist of myeloid clonal hemopathies with a diverse range of presentation. Until recently, there have been relatively few new therapies in the myelodysplastic syndromes treatment landscape. On April 3, 2020 the US Food and Drug Administration approved Reblozyl®(luspatercept-aamt), then on July 7, 2020, the US Food and Drug Administration approved INQOVI® (decitabine and cedazuridine). Luspatercept-aamt acts as a erythroid maturation agent through differentiation of late-stage erythroid precursors. The safety and efficacy of luspatercept-aamt was demonstrated in the MEDALIST trial, a phase III trial in patients with very low-intermediate risk refractory myelodysplastic syndromes and ring sideroblasts. Luspatercept-aamt met both primary and secondary endpoints of transfusion independence of 8 weeks or longer and transfusion independence of 12 weeks or longer, respectively. Decitabine/cedazuridine has a unique mechanism of action in which decitabine acts as a nucleoside metabolic inhibitor promoting DNA hypomethylation and cedazuridine then prevents degradation of decitabine. The safety and efficacy of decitabine/cedazuridine was shown in the ASCERTAIN study, a phase III trial in patients with intermediate or high risk myelodysplastic syndromes or chronic myelomonocytic leukemia. The primary outcome evaluated was 5-day cumulative area under the curve between decitabine/cedazuridine and IV decitabine as well as additional outcomes including safety. Decitabine/cedazuridine met primary outcome and had a similar safety profile to IV decitabine. Conclusion The novel myelodysplastic syndromes agents luspatercept-aamt and decitabine/cedazuridine provide a clinical benefit in the studied populations.

Biosimilar epoetin for cancer and chemotherapy-induced anaemia in the US

2021 ◽  
Vol 10 (3) ◽  
pp. 122-122
Author(s):  
Charles L Bennett
Keyword(s):  
Advisory Committee ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Safety And Efficacy ◽  
Biological Drug ◽  
Drug Products ◽  
Fda Approval ◽  
The Us ◽  
Approval Letter

Biosimilars are biological drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety and efficacy. Biosimilar epoetin received US Food and Drug Administration (FDA) approval in 2018 [1]. The manufacturer received an FDA non-approval letter in 2017, despite receiving a favourable review by the FDA’s Oncologic Drugs Advisory Committee (ODAC) and an FDA non-approval letter in 2015 for an earlier formulation.

scholarly journals Use, Safety, and Efficacy of Single-Patient Use of the US Food and Drug Administration Expanded Access Program

JAMA Oncology ◽  
2019 ◽  
Vol 5 (4) ◽  
pp. 570 ◽  
Author(s):  
Noah Z. Feit ◽  
Debra A. Goldman ◽  
Evan Smith ◽  
Jenny Deighan ◽  
Alexia Iasonos ◽  
...  
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
Single Patient ◽  
Safety And Efficacy ◽  
Expanded Access ◽  
Expanded Access Program ◽  
The Us ◽  
Patient Use ◽  
Access Program

Changing the Paradigm in the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer: From Platinum Doublets to Nonplatinum Doublets and Adding Antiangiogenesis Compounds

2009 ◽  
Vol 19 (Suppl 2) ◽  
pp. S63-S67 ◽  
Author(s):  
Bradley J. Monk ◽  
Robert L. Coleman
Keyword(s):  
Ovarian Cancer ◽  
Drug Administration ◽  
Liposomal Doxorubicin ◽  
Food And Drug Administration ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Platinum Sensitive ◽  
The Us

Objectives:The optimal treatment for women with recurrent epithelial ovarian cancer is evolving. The objective of this review is to outline the transition away from platinum doublets toward nonplatinum combinations and review emerging data on antiangiogenesis therapy in this setting.Materials and Methods:Recently published and presented data as well as ongoing clinical trials are discussed.Results:Current clinical practice largely harmonizes with a paradigm that outlines a treatment algorithm for recurrent ovarian cancer based on the duration of platinum-free exposure. In this model, patients whose penultimate platinum compound exposure (platinum-free interval [PFI]) is longer than 6 months are generally offered a platinum agent or a platinum-containing doublet; those with a shorter interval are usually treated with a single nonplatinum agent. This is based on the simple contention that better clinical outcomes will be realized with platinum in those deemed platinum sensitive (PFI >6 months). However, it is becoming clear from various phase II and phase III clinical studies that the performance of many nonplatinum chemotherapeutic agents is also influenced by this parameter (PFI). Indeed, although definitive comparisons of nonplatinum drugs to novel cytotoxic agents are lacking, the clinical activity of these compounds might approach or exceed that of platinum agents. Although recognized by clinicians, the dichotomy that determines therapy based on PFI has not been formally accepted by the US Food and Drug Administration in all cases of drug labeling. For instance, whereas the combination of gemcitabine and carboplatin is now approved for patients with platinum-sensitive recurrent ovarian cancer, traditionally used platinum-resistant (PFI <6 months) agents such as topotecan and pegylated liposomal doxorubicin are also approved by the US Food and Drug Administration as single agents in platinum-sensitive patients. Furthermore, the nonplatinum doublet pegylated liposomal doxorubicin and trabectedin has recently documented comparable activity to platinum combinations among patients with a PFI of longer than 6 months. To that end, the most prolific developmental therapeutics arena in ovarian cancer is biologically targeted therapy, particularly angiogenesis inhibitors. Although it is unknown if the clinical activity from these new agents will respect the chemotherapy-sensitive dichotomy, it is clear that they have the potential to augment efficacy, possibly in both traditionally chemosensitive and chemoresistant phenotypes.Conclusions:The term platinum sensitive should probably be replaced by chemotherapy sensitive, particularly as new nonplatinum agents and combinations are identified as active in this setting. Nonplatinum doublets are effective in treating platinum-sensitive recurrent disease, and adding antiangiogenesis agents to these combinations is a research priority.

Ultimate Fate of Oncology Drugs Approved by the US Food and Drug Administration Without a Randomized Trial

2009 ◽  
Vol 27 (36) ◽  
pp. 6243-6250 ◽  
Author(s):  
Apostolia-Maria Tsimberidou ◽  
Fadi Braiteh ◽  
David J. Stewart ◽  
Razelle Kurzrock
Keyword(s):  
Clinical Trials ◽  
Randomized Trial ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Objective Response ◽  
End Points ◽  
Median Response ◽  
Safety And Efficacy ◽  
The Us

Purpose To approve a new anticancer drug, the US Food and Drug Administration often requires randomized trials. However, several oncology drugs have been approved on the basis of objective end points without a randomized trial. We reviewed the long-term safety and efficacy of such agents. Methods We searched the Web site of the US Food and Drug Administration's Center for Drug Evaluation and Research and MEDLINE for initial applications of investigational anticancer drugs from 1973 through 2006. Results Overall, 68 oncology drugs, excluding hormone therapy and supportive care, were approved, including 31 without a randomized trial. For these 31 drugs, a median of two clinical trials (range, one to seven) and 79 patients (range, 40 to 413) were used per approval. Objective response was the most common end point used for approval; median response rate was 33% (range, 11% to 90%). Thirty drugs are still fully approved. United States marketing authorization for one drug, gefitinib (an epidermal growth factor receptor [EGFR] inhibitor), was rescinded after a randomized trial showed no survival improvement; however, this trial was performed in unselected patients, and it was subsequently demonstrated that patients with EGFR mutation are more likely to respond. Nineteen of the 31 drugs have additional uses (per National Comprehensive Cancer Network or National Cancer Institute Physician Data Query guidelines), and subsequent formal US Food and Drug Administration approvals were obtained for 11 of these (range, one to 18 new indications). No drug has demonstrated safety concerns. Conclusion Nonrandomized clinical trials with definitive end points can yield US Food and Drug Administration approvals, and these drugs have a reassuring record of long-term safety and efficacy.

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