General Information

Iwilfin (eflornithine) is an ornithine decarboxylase inhibitor.

Iwilfin is specifically indicated to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB) who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy.

Dosing/Administration

Prior to initiating Iwilfin, perform complete blood count, liver function tests, and baseline audiogram.

• Administer Iwilfin orally twice daily, with or without food, for two years or until recurrence of disease or unacceptable toxicity.
• Iwilfin tablets can be swallowed whole, chewed, or crushed.
• A missed dose of Iwilfin should be administered as soon as possible. If the next dose is due within 7 hours, the missed dose should be skipped.
•  If vomiting occurs after taking Iwilfi, an additional dose should not be administered. Continue with the next scheduled dose
  

The recommended Iwilfin dosage is based on body surface area (BSA). Recalculate the BSA dosage every 3 months during treatment with Iwilfin. See drug prescribing label for various dose modifications.

Mechanism of Action

Iwilfin (eflornithine) is an irreversible inhibitor of the enzyme ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines and a transcriptional target of MYCN. Polyamines are involved in differentiation and proliferation of mammalian cells and are important for neoplastic transformation. Inhibition of polyamine synthesis by eflornithine restored the balance of the LIN28/Let-7 metabolic pathway, which is involved in regulation of cancer stem cells and glycolytic metabolism, by decreasing expression of the oncogenic drivers MYCN and LIN28B in MYCN-amplified neuroblastoma. In vitro, eflornithine induced senescence and suppressed neurosphere formation in MYCN-amplified and MYCN non-amplified neuroblastoma cells, indicating a cytostatic effect. Treatment with eflornithine prevented or delayed tumor formation in mice injected with limiting dilutions of MYCN-amplified neuroblastoma cells.

Side Effects

Adverse effects associated with the use of Iwilfin may include, but are not limited to, the following:

• hearing loss
• otitis media
• pyrexia
• pneumonia
• diarrhea
• Grade 3 or 4 laboratory abnormalities (incidence ≥2%): increased ALT, increased AST, decreased neutrophil count, and decreased hemoglobin

Clinical Trial Results

The FDA approval of Iwilfin was based on results of a multi-site, single-arm, externally controlled study of children with high-risk neuroblastoma who received Iwilfin as maintenance therapy following standard of care treatment, including immunotherapy. The study demonstrated that the addition of Iwilfin improved event-free survival (EFS) and overall survival (OS) in patients with high-risk neuroblastoma. At four years following immunotherapy, EFS in the IWILFIN-treated patient group was 84% compared to 73% of patients in the external control group, and 96% of patients treated with Iwilfin were alive compared to 84% of external control patients. This corresponded to a 52% reduction in the risk of relapse and a 68% reduction in the risk of death. Across additional analyses to confirm the results of the externally controlled study design, the relapse risk reduction ranged from 57% to 41% and death risk reduction ranged from 71% to 55%.