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The FDA approved oral eflornithine (Iwilfin) for children and adults with high-risk neuroblastoma, the on Wednesday.

Specifically, the ornithine decarboxylase inhibitor is indicated as a maintenance therapy in patients achieving at least a partial response to standard multiagent, multimodality treatment that includes an anti-GD2 immunotherapy -- i.e., dinutuximab (Unituxin) or naxitamab (Danyelza).

It represents the first approval of a drug intended to lower the relapse risk for neuroblastoma in kids, a population that accounts for at least 90% of all new cases, the agency said. More than half of cases are classified as high-risk.

Neuroblastomas typically form in immature nerve tissue (neuroblasts) of the adrenal glands, neck, chest, or spinal cord, and the tumor type represents the most common solid tumor in childhood outside of central nervous system cancers, .

Each year, over 650 new cases of neuroblastoma are diagnosed in the U.S. The disease carries a 5-year survival rate of 91% for infants and 83% for kids ages 1 to 14 years.

Approval of eflornithine followed an October endorsement from the FDA's Oncologic Drugs Advisory Committee, which by a 14-6 vote determined there was sufficient evidence to show that maintenance treatment with the agent improved event-free survival (EFS).

Primary support came from a of eflornithine-treated patients compared against a historic control from the Children's Oncology Group . The efficacy analysis included 90 patients treated with twice-daily eflornithine tablets (with dosage based on patients' body surface area) and a matched group of 270 patients from ANBL0032.

The primary analysis showed that maintenance treatment with the agent was associated with a 52% reduced risk of progression, relapse, secondary cancers, or death (HR for EFS 0.48, 95% CI 0.27-0.85). Likewise, overall survival (OS) significantly favored the eflornithine-treated group (HR for OS 0.32, 95% CI 0.15-0.70).

At 4 years after anti-GD2 immunotherapy, EFS and OS rates reached 84% and 96%, respectively, for the eflornithine-treated group, as compared with 73% and 84% among the external controls, according to a announcing the approval from drugmaker US WorldMeds.

"After diligent efforts for the past decade, I am both humbled and overjoyed to see this product that holds the potential to evolve the standard of care for high-risk neuroblastoma come to fruition," Giselle Saulnier Sholler, MD, of Penn State Health Children's Hospital in Hershey, Pennsylvania, and the chair and founder of Beat Childhood Cancer Research Consortium, said in a statement.

Supplementary analyses, performed because of uncertainties of the effect size due to the non-randomized study design, suggested HRs for EFS ranging from 0.43 (95% CI 0.23-0.79) to 0.59 (95% CI 0.28-1.27) in subpopulations or with alternative statistical methods, the FDA said. For OS, these analyses showed HRs ranging from 0.29 (95% CI 0.11-0.72) to 0.45 (95% CI 0.21-0.98).

According to the drug's label, eflornithine is an irreversible inhibitor of ornithine decarboxylase, an enzyme involved in the biosynthesis of polyamines (which are important for neoplastic transformation) and a target of MYCN, an oncogene.

The lists no contraindications, but warnings and precautions include myelosuppression, hepatotoxicity, hearing loss, and embryo-fetal toxicity. A baseline audiogram along with complete blood count and liver function tests should be performed prior to eflornithine initiation, according to the label.

The twice-daily tablets can be swallowed whole (with or without food), chewed, or crushed up and mixed into foods or liquids. Treatment is given for a maximum of 2 years if disease does not progress and if there is no unacceptable toxicity.

Common adverse events (≥5%) in patients treated with eflornithine included otitis media, diarrhea, cough, sinusitis, pneumonia, conjunctivitis, vomiting, pyrexia, allergic rhinitis, decreased neutrophils, increased liver enzymes, hearing loss, and infections of the skin, urinary tract, and upper respiratory tract. Common grade 3/4 laboratory abnormalities (≥2%) included increases in liver enzymes and decreases in neutrophils and hemoglobin.

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