FDA Grants Fast Track Designation to Betalutin for Follicular Lymphoma

The US Food and Drug Administration (FDA) has granted Fast Track designation in the United States to Nordic Nanovector ASA’s 177lu-lilotomab satetraxetan (Betalutin) for the treatment of patients with relapsed or refractory follicular lymphoma (FL) who have had a least 2 previous systemic therapies.

“We are pleased to have been granted Fast Track designation for Betalutin. This designation is based on the promising safety and preliminary efficacy data in patients with relapsed/refractory indolent non-Hodgkin’s lymphoma from the first part of the LYMRIT 37-01 study and highlights the potential of Betalutin to be a new therapeutic option for these patients,” Nordic Nanovector’s CMO, Lisa Rojkjaer, said in a recent statement.

Betalutin is an anti-CD37 antibody (lilotomab) conjugated to a low-intensity radionuclide (lutetium-177), according to Nordic Nanovector. The drug’s safety, pharmacokinetics, and activity were tested in phase 1/2 open-label LYMRIT 37-01 study in patients with relapsed indolent non-Hodgkin’s lymphoma (NHL). The study was conducted in 2 parts, with 29 patients enrolled in phase 1, which used dose escalation cohorts to identify the optimal cold antibody—lilotomab or rituximab—pre-dosing and drug regimen and 30 patients enrolled in phase 2, which expanded cohorts to confirm safety and efficacy.

Patients were enrolled into 4 dose-escalation arms; the first arm received the drug plus pre-dosing with 40 mg lilotomab (cold anti-CD37 Ab), the second arm just received Betalutin without pre-dosing, the third arm received the drug plus pre-dosing with rituximab, and the fourth arm received the drug plus pre-dosing with 100 mg/m² lilotomab. However, all patients enrolled in the study were administered rituximab as pre-treatment to improve biodistribution of the drug. Overall, the drug was found to be well-tolerated.

“We are now focusing the PARADIGME trial on 3L CD20-refractory FL patients, a population in urgent need of new therapies, and look forward to working with the FDA to advance the development of Betalutin,” Rojkjaer added.

The phase 2b PARADIGME clinical trial aims to enroll 130 patients spanning 80 to 85 sites in 20 different countries. For the study, investigators will compare 2 dosing regimens of the drug—15MBq/kg Betalutin following 40mg lilotomab pre-dosing and 10MBq/kg Betalutin following 100 mg/m² lilotomab pre-dosing—in 3L FL patients. Overall response rate (ORR) will be the primary endpoint of the study, while secondary endpoints will include duration of response, progression-free survival, and overall survival, as well as safety and quality of life.

Nordic Nanovector predicts that an initial efficacy and safety data read-out for the trial will be available in the first half of 2020.

Follicular lymphoma is a slow-growing form of NHL that is characterized by a proliferation of B-cells, making it a B-cell lymphoma, a subtype that accounts for 20% to 30% of all NHL cases, according to the Lymphoma Research Foundation.