The U.S. Food and Drug Administration (FDA) approved Endari in July 2017 to treat SCD patients, age 5 and older. This decision made Endari the first approved treatment for children with sickle cell disease, and the first new treatment for adults with the disease in almost 20 years.
How does Endari work?
People with sickle cell disease have an altered form of hemoglobin that renders red blood cells susceptible to oxidation damage. (Hemoglobin is the protein in red blood cells that carries oxygen.)
High oxidative stress increases the stiffness of these red blood cells, leading to their sickle-like shape. Less flexible than healthy (and round) red blood cells, these abnormal cells often stick to blood vessel walls, slowing or blocking blood flow and oxygen transport.
Glutamine plays various fundamental roles in cell metabolism. These include protein synthesis, and energy and anti-oxidant production. The body naturally produces glutamine to counter infection, injury, and stress.
Endari works to increase the amount of free glutamine circulating in the blood. Sickle cells can take up this free glutamine and use it to generate anti-oxidant molecules. These new antioxidants can help neutralize the oxidative stress in sickle cells. This can allow them to regain the flexibility necessary to travel through blood vessels and capillaries, carrying oxygen to tissues throughout the body.
Endari in clinical trials
Three clinical trials assessed the effectiveness of Endari in treating sickle cell anemia and sickle beta-thalassemia.
The first trial, which ended in 2008, was a Phase 2 double-blind and randomized study (NCT00125788). It evaluated the number of sickle cell crises experienced by patients with sickle cell anemia or sickle beta-thalassemia over 48 weeks of treatment in comparison with those on a placebo.
A second Phase 2 study (NCT00586209) that ended in 2009 evaluated the effectiveness of Endari, again versus placebo, in 18 patients with sickle cell anemia or sickle beta-thalassemia. Its focus was on improvements in exercise endurance and breath, and the number of disease crises. This was measured by pain levels and narcotics use, changes in energy and appetite, and hospital and emergency room visits over 28 days.
A pivotal Phase 3 randomized, double-blind and placebo-controlled study (NCT01179217) evaluated the effects of Endari in 230 patients, ages 5 and older, with sickle cell anemia or sickle cell thalassemia. The U.S.-based trial concluded in 2014, and results were published in 2018.
The trial compared 48 weeks of treatment with oral Endari or a placebo (maltodextrin, a food additive), measured in terms of differences in sickle cell crises, hospitalizations and emergency room or medical visits, hematological parameters, and adverse reactions between the two groups. Trial results showed that Endari’s use led to a 25% reduction in the median frequency of pain crises, and a 33% median decrease in hospitalization rates. The treatment was also reported to be safe and well tolerated. Of the 230 people enrolled, 156 patients completed the trial, 97 in the Endari group (63.8%) and 59 in the placebo group (75.6%).
This study was the basis of Emmaus’ application to the FDA requesting approval, which the regulatory agency accepted for review in November 2016.
Reported common side effects of Endari’s use can include constipation, nausea, headache, cough, abdominal pain, and pain in the extremities, back, and chest.
Emmaus launched the Endari Support Program (ESP) in December 2020 to provide the treatment at minimal or no cost to patients in the U.S. who meet eligibility requirements according to income and insurance coverage. Go here for more details about the program and its eligibility criteria, or to start an application.
Emmaus withdrew an application with the European Medicines Agency (EMA) requesting Endari’s approval (to be available under the brand name Xyndari) in 2019 after a branch of Europe’s regulatory agency gave a negative review of treatment efficacy, while acknowledging safety.
Last updated: Feb. 8, 2021
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