1 INDICATIONS AND USAGE IWILFIN (eflornithine) is 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.

IWILFIN is an ornithine decarboxylase inhibitor 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.

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6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Hearing Loss [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥5%) are hearing loss, otitis media, pyrexia, pneumonia, and diarrhea.

( 6.1 ) Most common Grade 3 or 4 laboratory abnormalities (incidence ≥2%) are increased ALT, increased AST, decreased neutrophil count, and decreased hemoglobin.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact US WorldMeds at 1-877-IWILFIN or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in clinical practice.

The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to IWILFIN as a single agent, taken orally at doses ranging from 192 - 768 mg twice daily, based on body surface area (BSA), until disease progression, unacceptable toxicity, or for a maximum of 2 years in patients who demonstrated at least a partial response to prior multiagent, multimodality therapy for newly diagnosed or relapsed/refractory high-risk neuroblastoma in Study 3b (n=101; NCT02395666) and Study 14 (n=259; NCT02679144).

Among 360 patients who received IWILFIN, 84% were exposed for 6 months or longer and 73% were exposed for greater than one year.

In this pooled safety population, the most common (≥5%) adverse reactions were hearing loss (11%), otitis media (10%), pyrexia (7%), pneumonia (5%), and diarrhea (5%).

The most common (≥2%) Grade 3 or 4 laboratory abnormalities were increased ALT (11%), increased AST (6%), decreased neutrophils (4.2%), and decreased hemoglobin (3.3%).

Study 3b The safety of IWILFIN was evaluated in Study 3b [see Clinical Studies (14.1)] .

Eligible patients were pediatric patients with high-risk neuroblastoma (HRNB) who demonstrated at least a partial response to prior multiagent, multimodality therapy including induction, consolidation, and anti-GD2 immunotherapy.

Patients received IWILFIN as a single agent taken orally at doses ranging from 192 - 768 mg twice daily, based on body surface area (BSA), until disease progression, unacceptable toxicity, or for a maximum of 2 years (N=85).

Among patients who received IWILFIN, 93% were exposed for 6 months or longer and 89% were exposed for greater than one year.

The median age of patients who received IWILFIN was 4 years (range: 1 to 17); 59% male; 85% White, 7% Black, 1% Asian, 8% Hispanic or Latino; 87% had International Neuroblastoma Staging System Stage 4 disease; 47% had neuroblastoma with known MYCN-amplification.

Serious adverse reactions occurred in 12% of patients who received IWILFIN.

Serious adverse reactions in >1 patient included skin infection (3 patients).

Permanent discontinuation of IWILFIN due to an adverse reaction occurred in 11% of patients.

Adverse reactions which resulted in permanent discontinuation of IWILFIN in >1 patient included hearing loss.

Dose reductions of IWILFIN due to an adverse reaction occurred in 8% of patients.

Adverse reactions which required dose reductions in >1 patient included hearing loss.

The most common (≥5%) adverse reactions, including laboratory abnormalities, were otitis media, diarrhea, cough, sinusitis, pneumonia, upper respiratory tract infection, conjunctivitis, vomiting, pyrexia, allergic rhinitis, decreased neutrophils, increased ALT, increased AST, hearing loss, skin infection, and urinary tract infection.

Table 5 summarizes the adverse reactions in Study 3b.

Table 5: Adverse Reactions (≥5%) in Patients with HRNB Who Received IWILFIN in Study 3b Adverse Reaction Severity as defined by CTCAE Version 4.03.

IWILFIN (n=85) All Grades Grade 1 adverse events were not comprehensively collected in Study 3b.

, No Grade 4 or 5 events were reported.

(%) Grade 3 (%) Infections Otitis media 32 2.4 Sinusitis 13 0 Pneumonia 12 1.2 Upper respiratory tract infection 11 0 Conjunctivitis 11 0 Skin infection 7 4.7 Urinary tract infection 6 1.2 Gastrointestinal Disorders Diarrhea Includes colitis.

15 3.5 Vomiting 11 1.2 Respiratory Disorders Cough 15 0 Allergic rhinitis 11 0 General Disorders Pyrexia 11 1.2 Ear and Labyrinth Disorders Hearing loss 7 7 Clinically relevant adverse reactions in <5% of patients who received IWILFIN included rash, extremity pain, and alopecia.

Table 6 summarizes the laboratory abnormalities in Study 3b.

Table 6: Select Laboratory Abnormalities (≥1%) in Patients with HRNB Who Received IWILFIN in Study 3b Laboratory Abnormality Severity as defined by CTCAE Version 4.03.

IWILFIN (n=85) All Grades Grade 1 adverse events were not comprehensively collected in Study 3b.

, No Grade 5 events occurred.

(%) Grade 3 or 4 (%) Chemistry Increased ALT 9 7 No Grade 4 events occurred.

Increased AST 8 6 Increased alkaline phosphatase 4.7 2.4 Decreased potassium 2.4 2.4 Decreased glucose 2.4 1.1 Decreased sodium 2.4 2.4 Increased potassium 1.2 0 Increased glucose 1.2 0 Hematology Decreased neutrophils 9 8 Decreased hemoglobin 4.7 2.4 Decreased white blood cells 2.4 0 Decreased platelets 1.2 0