Melflufen (Ygalo®), an peptide conjugated alkylator belonging to a novel class of peptidase-enhanced compounds, targets multiple myeloma (MM) cells with a unique mechanism of action. Aminopeptidases are enzymes found in all cells but are over-expressed in several cancers including MM. Melflufen selectively targets MM cells through aminopeptidase-driven accumulation. In vitro experiments show a 50-fold enrichment of the active substance in MM cells compared with administration of equal amount of an alkylator not enriched by aminopeptidases. The enrichment results in selective cytotoxicity (increased on-target potency and decreased off-target toxicity), and that resistance pathways of existing myeloma treatments (including alkylators) is overcome. Melflufen also demonstrates strong anti-angiogenic properties.
Melflufen is intended to be the first choice for the treatment of patients with late-stage relapsed and refractory multiple myeloma. Multiple myeloma is a haematological cancer with no cure and a median survival period of approximately 5 years from diagnosis. Patients in the late stages of multiple myeloma suffer from symptoms including skeletal pain, bone fractures and infections associated with a weakened immune system as well as from the side effects of the treatments available today.
Comparing clinical data between melflufen and the current standard of care in multiple myeloma indicates that treatment with melflufen increases overall survival, progression free survival and the number of patients with significant tumour burden reduction as well as being better tolerated by patients.
The pivotal Phase 3 clinical study (OCEAN, OP-103) is currently enrolling and has been approved under the US Food and Drug Administration’s Special Protocol Assessment. In the OCEAN study, melflufen is compared directly against the current standard of care in patients with relapsed or refractory multiple myeloma.
As a rare condition, multiple myeloma is classified as an orphan disease in the US and Europe and melflufen has been granted orphan drug designation by the relevant authorities in both these jurisdictions.