Melphalan Flufenamide (Melflufen): First Approval

This review describes the recent Food and Drug Administration (FDA)-approved drugs (in the year 2021) containing at least one halogen atom (covalently bound). The structures proposed throughout this work are grouped according to their therapeutical use. Their synthesis is presented as well. The number of halogenated molecules that are reaching the market is regularly preserved, and 14 of the 50 molecules approved by the FDA in the last year contain halogens. This underlines the emergent role of halogens and, in particular, of fluorine and chlorine in the preparation of drugs for the treatment of several diseases such as viral infections, several types of cancer, cardiovascular disease, multiple sclerosis, migraine and inflammatory diseases such as vasculitis.

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“…Chemically, it is the ethyl ester of a lipophilic dipeptide consisting of melphalan and para -fluoro- l -phenylalanine [ 32 ].…”

Section: New Halogen-containing Drugsmentioning

confidence: 99%

New Halogen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use

et al. 2022

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“…The released, less lipophilic melphalan becomes trapped and achieves much higher intracellular concentrations than those observed upon direct melphalan exposure (Wickstrom et al 2017 ). Melphalan flufenamide is currently being tested for amyloid light-chain amyloidosis and various hematological and solid cancers (Dhillon 2021b ). While cytopenias were the most common AE, alopecia and mucositis did not occur with melphalan flufenamide (Ocio et al 2020 ).…”

Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition (“first-in-indication”), (2) first drug using a novel molecular mechanism (“first-in-class”), and (3) “next-in-class”, i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indication drugs. By treatment area, the largest group is once again cancer drugs, many of which target specific genetic alterations. Every second drug approved in 2021 targets an orphan disease, half of them being cancers. Small molecules continue to dominate new drug approvals, followed by antibodies and non-antibody biopharmaceuticals. In 2021, the FDA continued to approve drugs without strong evidence of clinical effects, best exemplified by the aducanumab controversy.

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“…Within cells, melflufen can be processed by aminopeptidase to release free melphalan for function . By 2021, melflufen had been temporally approved by the FDA for relapsed or refractory MM (RRMM) treatment . The other melphalan modifications were mainly in preclinical stages.…”

Section: Discussionmentioning

confidence: 99%

“… 14 By 2021, melflufen had been temporally approved by the FDA for relapsed or refractory MM (RRMM) treatment. 15 The other melphalan modifications were mainly in preclinical stages. Several researchers synthesized melphalan derivatives, chemically modified melphalan, to achieve superior anti-MM activity.…”

Section: Discussionmentioning

confidence: 99%

Liposome-Encapsulated Melphalan Exhibits Potent Antimyeloma Activity and Reduced Toxicity

Zheng

Chu

et al. 2022

ACS Omega

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Multiple myeloma (MM), a plasma cell cancer in bone marrow, remains an incurable disease. Melphalan, an alkylating agent, is a conventional anticancer drug that is still widely used for MM treatment in clinics. However, melphalaninduced organ toxicity and side effects are common. In this study, we loaded melphalan into a liposomal capsule and constituted liposomal melphalan (liposomal MEL). Liposomal MEL particles were approximately 120 nm in size and stable in vitro. The liposomal particles could be effectively taken up by MM cells. In vitro cytotoxicity assays using MM cell lines and primary MM cells showed that liposomal MEL exhibited similar anti-MM activity compared to an equivalent amount of free melphalan (free MEL) compound. In animal models, liposomal particles had bone marrow enrichment and prolonged half-life in vivo. Liposomal MEL exposure resulted in less liver and colon organ toxicity than exposure to an equivalent amount of free MEL-treated mice. Importantly, liposomal MEL had potent anti-MM activity in vivo in a human MM xenograft mouse model. Overall, our findings suggested that liposome-encapsulated melphalan was an effective drug modification of the melphalan compound and showed promise in MM treatment.

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Melphalan Flufenamide (Melflufen): First Approval

Cited by 40 publications

References 17 publications

New Halogen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use

New Halogen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Liposome-Encapsulated Melphalan Exhibits Potent Antimyeloma Activity and Reduced Toxicity

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