Difference between revisions of "Melphalan flufenamide (Pepaxto)"
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| − | <big>'''Note: this drug has been withdrawn from the US market | + | <big>'''Note: this drug has been withdrawn from the US market.'''</big> |
==Mechanism of action== | ==Mechanism of action== | ||
| Line 8: | Line 8: | ||
==History of changes in FDA indication== | ==History of changes in FDA indication== | ||
| − | * | + | ===[[Multiple myeloma]] - '''WITHDRAWN'''=== |
| + | *2021-02-26: Granted accelerated approval to in combination with dexamethasone for adult patients with relapsed or refractory [[multiple myeloma]] who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD-38 directed monoclonal antibody. ''(Based on HORIZON<sub>RRMM</sub>)'' | ||
| + | **2024-02-23: Accelerated approval withdrawn. ''(Based on OCEAN)'' | ||
| + | |||
| + | ==History of changes in EMA indication== | ||
| + | *2022-08-17: Initial authorization as Pepaxti. Pepaxti is indicated, in combination with dexamethasone, for the treatment of adult patients with [[multiple myeloma]] who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one antiCD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. For patients with a prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation. | ||
| + | *Future date (positive CHMP summary of opinion): Pepaxti is indicated, in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior lines of therapies, whose disease is refractory to lenalidomide and the last line of therapy. | ||
==Also known as== | ==Also known as== | ||
*'''Code name:''' J1 | *'''Code name:''' J1 | ||
*'''Generic name:''' melflufen | *'''Generic name:''' melflufen | ||
| − | *'''Brand named:''' Pepaxto, Ygalo | + | *'''Brand named:''' Pepaxti, Pepaxto, Ygalo |
[[Category:Drugs]] | [[Category:Drugs]] | ||
| + | [[Category:Intravenous medications]] | ||
[[Category:Peptide-drug conjugates]] | [[Category:Peptide-drug conjugates]] | ||
[[Category:Alkylating agents]] | [[Category:Alkylating agents]] | ||
| Line 21: | Line 28: | ||
[[Category:Multiple myeloma medications]] | [[Category:Multiple myeloma medications]] | ||
[[Category:FDA approved in 2021]] | [[Category:FDA approved in 2021]] | ||
| + | [[Category:FDA withdrawn in 2024]] | ||
| + | [[Category:EMA approved in 2022]] | ||
Latest revision as of 11:29, 9 April 2024
Note: this drug has been withdrawn from the US market.
Mechanism of action
From the NCI Drug Dictionary: A peptide-drug conjugate composed of a peptide conjugated, via an aminopeptidase-targeting linkage, to the alkylating agent melphalan, with potential antineoplastic and anti-angiogenic activities. Upon administration, the highly lipophilic melphalan flufenamide penetrates cell membranes and enters cells. In aminopeptidase-positive tumor cells, melphalan flufenamide is hydrolyzed by peptidases to release the hydrophilic alkylating agent melphalan. This results in the specific release and accumulation of melphalan in aminopeptidase-positive tumor cells. Melphalan alkylates DNA at the N7 position of guanine residues and induces DNA intra- and inter-strand cross-linkages. This results in the inhibition of DNA and RNA synthesis and the induction of apoptosis, thereby inhibiting tumor cell proliferation. Peptidases are overexpressed by certain cancer cells. The administration of melphalan flufenamide allows for enhanced efficacy and reduced toxicity compared to melphalan.
Diseases for which it is used
History of changes in FDA indication
Multiple myeloma - WITHDRAWN
- 2021-02-26: Granted accelerated approval to in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD-38 directed monoclonal antibody. (Based on HORIZONRRMM)
- 2024-02-23: Accelerated approval withdrawn. (Based on OCEAN)
History of changes in EMA indication
- 2022-08-17: Initial authorization as Pepaxti. Pepaxti is indicated, in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one antiCD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. For patients with a prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation.
- Future date (positive CHMP summary of opinion): Pepaxti is indicated, in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior lines of therapies, whose disease is refractory to lenalidomide and the last line of therapy.
Also known as
- Code name: J1
- Generic name: melflufen
- Brand named: Pepaxti, Pepaxto, Ygalo