Melflufen is a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. It belongs to the novel class Peptidase Enhanced Cytotoxics (PEnC), which is a family of lipophilic peptides that exhibit increased activity via peptidase cleavage and have the potential to treat many cancers. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the peptidase cleavage, and induces irreversible DNA damage and apoptosis. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.
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.