FDA clears Y-mAbs' Danyelza for high-risk neuroblastoma in bone or bone marrow

Y-mAbs Therapeutics announced that the FDA granted accelerated approval to the monoclonal GD2 antibody Danyelza (naxitamab-gqgk) for the treatment of certain patients with neuroblastoma. The drug, also known as Hu3F8, is indicated for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in adults and paediatric patients 1 year and older with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy.

The decision is based on a review of data from the single-arm, ongoing 201 and 12-230 trials, the latter of which is being conducted in collaboration with the Memorial Sloan Kettering Cancer Center (MSK), which developed Danyelza. Study 201 has an estimated enrolment of 95 patients, while Study 12-230 is expected to recruit about 224 participants.

Patients received Danyelza via intravenous infusion on days 1, 3 and 5 of each four-week cycle in combination with subcutaneous GM-CSF, which was also administered on a specific dosing schedule. At the investigator's discretion, patients were permitted to receive pre-planned radiation to the primary disease site in Study 201 and radiation therapy to non-target bony lesions or soft tissue disease in Study 12-230. The main efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR).

According to the FDA, among 22 patients treated in Study 201, the ORR was 45%, with 30% of responders having a DOR of six months or more. Further, among 38 patients treated in Study 12-230, the ORR was 34%, while 23% of patients achieved a DOR greater or equal to six months. The agency noted that in both trials, responses were observed in either the bone, bone marrow or both.

'Much-needed' treatment

CEO Claus Moller said the approval of Y-mAbs' first biologics license application represents "a much-needed treatment for patients with relapsed/refractory high-risk neuroblastoma in the bone or bone marrow who have historically not had approved treatments available." The company said Danyelza is expected to be introduced in the US in the coming weeks.

The label for Danyelza comes with a boxed warning about the risk for serious infusion-related reactions and neurotoxicity, including severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome. Adverse reactions that occurred in more than a quarter of participants in either trial included infusion-related reactions, pain, tachycardia and vomiting, among others. Meanwhile, Grade 3 or 4 laboratory abnormalities occurring in at least 5% of patients in either trial included decreased white blood cell counts, as well as lower levels of haemoglobin and various electrolytes, plus increased alanine aminotransferase.

Danyelza was previously granted orphan drug and rare paediatric disease designations by the FDA. The drug is exclusively licensed to Y-mAbs by MSK, which has institutional financial interests related to the compound and the company.

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