Betalutin® is the first of a new generation of Antibody-Radionuclide-Conjugates (ARC) that is currently undergoing clinical testing and is being developed as a potential new treatment of relapsed non-Hodgkin Lymphoma (NHL).
Betalutin® consists of the murine antibody lilotomab (formerly referred to as HH1), which targets the CD37 antigen on the surface of NHL cells conjugated to the beta-emitting isotope lutetium-177 (Lu-177) via the chemical linker DOTA.
Key benefits of Betalutin® include:
- Betalutin® targets CD37, a different antigen compared to other drugs for NHL.
CD37 is expressed by adult B-cells and is present on the majority of B-cell lymphoma cells. It is an ideal therapeutic target for CD37-based ARC therapies in relapsed lymphoma patients that do not respond to standard CD20-based therapy (rituximab) providing greater anticipated activity and a potential synergistic effect.
- The Lu-177 payload is a low intensity beta emitter with a range of approximately 0.5 millimetres (i.e. ~ 50-cell radius). Beta particles cause tumour cell death through irreversible double-stranded DNA breaks and the limited range of the particles minimizes their impact on healthy cells.
- Betalutin® is rapidly internalized when bound to CD37 thereby anchoring the Lu-177 payload inside the cell and enabling a prolonged irradiation of tumour cells within the ~50-cell radius. This localized "multi-cell kill" mechanism of action (the ‘crossfire effect’) destroys malignant cells that do not express CD37 or that have limited blood supply within a tumour mass, and thereby offers a significant advantage over single-cell kill effected by immunotherapy and chemotherapy.
- The half-life of Lu-177 (6.7 days) matches the circulation time of lilotomab offering effective bio-distribution before either the antibody is recycled or the payload decays.
- Betalutin® is prepared as a ready-to-use formulation that is administered as a single injection in an outpatient setting. Manufacture and logistics are straightforward.
Illustration of how Betalutin® attaches itself to the CD37 antigen and delivers a lethal dose of Beta radiation to a lymphoma