Betalutin is an injectable potential treatment being developed by Nordic Nanovector for patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL).
How Betalutin works
Betalutin is an antibody-radionuclide conjugate. It is a form of radioimmunotherapy, where a radionuclide molecule (a compound that emits radiation and is able to kill cancer cells) is linked to an antibody (a compound that only binds to a specific target). This mechanism aims to allow antibody-radionuclide conjugates to deliver toxic radionuclide molecules directly to cancer cells only, killing them and sparing healthy cells.
In Betalutin, the radionuclide used is known as the beta particle-emitting isotope lutetium-177 (Lu-177), while the antibody component is known as lilotomab and targets a protein that specifically exists on the surface of NHL cells. Upon binding to cancer cells, Betalutin enters the cells and its Lu-177 component releases beta-particles that kills tumor cells by irreversibly breaking their DNA.
The unique property of beta-particles is that they can destroy tumor cells that exist in close proximity to the cells that the radionuclides are in, even if the surrounding cells do not express CD37 proteins, the company states. This is known as the ‘cross-fire effect’. Additionally, the Lu-177 beta-particles are able to damage cells within a 0.25mm radius only, which limits the damage to healthy cells surrounding the tumor.
Betalutin’s antibody component binds to the CD37 protein, which is highly expressed on the surface of NHL cancer cells, and not to the CD20 protein targeted by current NHL therapies like rituximab. Therefore, Betalutin may prove to be an alternative for patients who do not respond to standard CD20-based therapies.
Betalutin in clinical trials
Initial results from an open-label Phase 1/2 trial (NCT01796171) report that Betalutin treatment was able to shrink tumor size in 90 percent of the 59 advanced indolent NHL patients with incurable disease, including follicular lymphoma patients who had undergone three previous lines of treatment. Sixty percent of all patients experienced an overall response rate, with 24 percent having a complete response. Previously treated patients also responded to Betalutin (66 percent overall response rate and 25 percent complete response rate). Betalutin was well-tolerated and had an acceptable safety profile, with patients only experiencing temporary dips in their white blood cell and platelet counts and a few experiencing infections.
These results were presented at the International Conference on Malignant Lymphoma in Switzerland in 2017. The trial began in 2012 and is scheduled to end in 2021. It is currently actively recruiting participants at sites across Europe and the U.K.
Two other Phase 1 trials for Betalutin are also underway. The first (NCT02658968) seeks to investigate Betalutin in treating relapsed and treatment-unresponsive diffuse large B-cell lymphoma (a type of NHL) patients. It is currently recruiting at sites in the U.S., Europe, Italy, and the U.K. The trial began in 2016 and is expected to be completed in 2019.
A second Phase 1 trial (NCT02657447) aims to assess the safety, tolerability, pharmacokinetics (movement in the body), and amount of radiation released by different doses of Betalutin. The trial taking place in Germany is not yet open for recruitment. It is expected to finish in 2019.
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