Endari

Endari is indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. ENDARI is an amino acid indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older.

2 DOSAGE AND ADMINISTRATION 5 grams to 15 grams orally, twice daily based on body weight. Each dose of Endari should be mixed in 8 oz. (240 mL) of cold or room temperature beverage or 4 oz. to 6 oz. of food before ingestion.

2.1Dosage Administer Endari

orally, twice per day at the dose based on body weight according to Table 1. Table 1. Recommended Dosing Weight in kilograms Weight in pounds Per dose in grams Per day in grams Packets per dose Packets per day less than 30 less than 66 5 10 1 2 30 to 65 66 to 143 10 20 2 4 greater than 65 greater than 143 15 30 3 6

2.2Preparation of Product Mix Endari

immediately before ingestion with 8 oz. (240 mL) of cold or room temperature beverage, such as water, milk or apple juice, or 4 oz. to 6 oz. of food such as applesauce or yogurt. Complete dissolution is not required prior to administration. Dosage and Administration Advise patient to take a missed dose as soon as they remember.

Patient should not double the dose that they take . Instruct patient to mix each dose in 8 oz. (240 mL) of cold or room temperature beverage or 4 to 6 oz. of food. Advise patient that complete dissolution is not required prior to administration.

None None

8.1Pregnancy Risk Summary There

are no available data on Endari use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies were not conducted with Endari. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications.

The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Most common adverse reactions (incidence > 10%) are constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain. To report SUSPECTED ADVERSE REACTIONS, contact Emmaus Medical, Inc. at 1-877-420-6493 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical 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 the rates observed in practice. The data described below reflect exposure to Endari in 187 patients, including 136 exposed for 6 months and 109 exposed for ≥1 year. Endari was studied in 2 placebo-controlled clinical trials (a phase 3 study, n=230 and a phase 2 study, n=70).

In these trials, patients with sickle cell anemia or sickle β 0 -thalassemia were randomized to receive Endari (n=187) or placebo (n=111) orally twice daily for 48 weeks followed by 3 weeks of tapering. Both studies included pediatric and adult patients (5-58 years of age) and 54% were female. The majority of patients were black (97.3%), had a diagnosis of sickle cell anemia (89.9%) and were receiving hydroxyurea at baseline (63.4%).

Treatment discontinuation due to adverse reactions was reported in 2.7% (n=5) of patients receiving Endari. These adverse reactions included one case each of hypersplenism, abdominal pain, dyspepsia, burning sensation, and hot flash. Serious adverse reactions were reported in both treatment groups, more frequently in the placebo group, and were consistent with the underlying disease.

Three deaths (3/187=1.6%) occurred during the study in the Endari treatment group as compared to none in the placebo treatment group. None of the deaths were considered to be related to Endari treatment. Adverse reactions occurring in greater than 10% of patients treated with Endari are shown in Table 2 below.

Table 2. Adverse Reactions Occurring at an Incidence > 10% in Clinical Studies of Endari Adverse reaction Endari N = 187 (%) Placebo N = 111 (%) Constipation 21 18 Nausea 19 14 Headache 18 15 Abdominal Pain Abdominal pain = abdominal pain and abdominal pain, upper 17 16 Cough 16 14 Pain in extremity 13 7 Back pain 12 5 Chest pain 12 8