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Endariís Phase 3 trial results published in NEJM
TORRANCE, Calif.—Today Emmaus Life Sciences, Inc. announced that the New England Journal of Medicine (NEJM) has published the results of its 48-week Phase 3 clinical trial of Endari (L-glutamine oral powder), “A Phase 3 Trial of L-Glutamine in Sickle Cell Disease.” Endari is a prescription oral treatment approved by the U.S. Food and Drug Administration (FDA) to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older.
Sickle cell disease is an inherited blood disorder characterized by the production of an altered form of hemoglobin which polymerizes and becomes fibrous, causing red blood cells to become rigid and change form so they curve and appear sickle shaped, instead of soft and rounded. Patients with sickle cell disease suffer from debilitating episodes of sickle cell crises, which occur when the rigid, adhesive and inflexible red blood cells occlude blood vessels. Sickle cell crises cause excruciating pain as a result of insufficient oxygen being delivered to tissue, referred to as tissue ischemia, and inflammation. These events may lead to a variety of other adverse outcomes such as acute chest syndrome that requires hospitalization. Sickle cell disease is an orphan disease, affecting approximately 100,000 patients in the U.S. and millions worldwide, with significant unmet medical needs.
Endari was approved in July 2017, and is the first treatment in nearly 20 years shown to reduce the acute complications of sickle cell disease in adults when used as directed. Endari is also the first treatment approved to reduce the acute complications of sickle cell disease in children five years and older when used as directed. Endari has received Orphan Drug designation in the U.S., and Orphan Medicinal Product designation in the EU.
The article reports results that showed significantly fewer sickle cell crises in those receiving Endari compared to placebo by 25 percent and significantly fewer hospitalizations by 33 percent. Additional findings showed lower cumulative days in hospital of 41 percent and a lower incidence of acute chest syndrome (ACS) by more than 60 percent. The most common adverse reactions occurring in greater than 10 percent of the clinical study were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain and chest pain. Adverse reactions leading to treatment discontinuation included one case each of hypersplenism, abdominal pain, dyspepsia, burning sensation and hot flash. The safety and efficacy of Endari in pediatric patients with sickle cell disease younger than five years of age has not been established.
“Endari is the first approved treatment for sickle cell disease in pediatric patients 5 years of age and older and the first in nearly 20 years for adults. Our hope in sharing the results of this data from the New England Journal of Medicine, a publication with worldwide reach and significance, is to aid in increasing the awareness of sickle cell disease, a lifelong hereditary blood disorder which commonly affects those of African descent, as well as those from Central and South America and people of Middle Eastern, Asian, Indian and Mediterranean descent,” said co-author Yutaka Niihara, MD, CEO and founder of Emmaus.
The randomized, double-blind, placebo-controlled, multicenter Phase 3 trial evaluated the efficacy and safety of Endari (0.3 gram per kilogram of body weight per dose) administered twice daily by mouth, as compared with placebo. The study included patients at least 5 years of age with sickle cell anemia or sickle β0-thalassemia, with a history of two or more pain crises during the previous year. Patients who were receiving hydroxyurea at a dose that had been stable for at least 3 months before screening and who continued such therapy during the 48-week treatment period were eligible. A total of 230 patients (age range, 5 to 58 years; 53.9% female) were randomly assigned, in a 2:1 ratio, to receive L-glutamine (152 patients) or placebo (78 patients).
“Sickle cell disease affects thousands of people in the United States,” said Beverley Francis-Gibson, President and CEO of The Sickle Cell Disease Association of America, Inc. “While there is no universal cure for this life-threatening disease, patient awareness and education on treatment options remain important factors for the sickle cell community.”
Emmaus also announced July 9th that the FDA has accepted its Investigational New Drug (IND) application for L-glutamine as a treatment for diverticulosis. The FDA’s acceptance of the IND clears the way for Emmaus’ pilot study to assess the safety and efficacy of L-glutamine oral powder as a diverticulosis treatment. Emmaus expects to begin the study by the end of 2018. The interventional open-label, single-center pilot study will investigate the safety, tolerability and efficacy of L-glutamine treatment in approximately five to 10 patients with uncomplicated, asymptomatic diverticulosis over a period of 12 months.
“We’re grateful for the opportunity to move forward with studying the effects of L-glutamine for the treatment of diverticulosis, a common condition affecting millions of people in the U.S. alone,” Niihara noted. “The FDA’s acceptance of our IND application represents an important milestone as we look to help improve the well-being of those afflicted by this common condition.”
Patents have been issued for the use of L-glutamine in the treatment of diverticulosis in the United States, Japan, Australia, China, Mexico, Indonesia, South Korea, and Russia. Related patent applications are currently pending in Europe, Brazil, and India.