UCSF Benioff Children’s Hospital Oakland clinical researchers, in conjunction with other sickle cell centers and scientists at Emmaus Life Sciences, Inc., have demonstrated that therapy with L-glutamine reduced the frequency of pain episodes in both pediatric and adult patients with sickle cell disease (SCD). The results of the 48-week, phase 3 clinical trial are published in the July 19, 2018, issue of New England Journal of Medicine (NEJM).

The paper, “A Phase 3 Trial of L-Glutamine in Sickle Cell Disease,” documented the effects of taking Endari™, a prescription-grade, pharmaceutical form of L-glutamine, as compared to placebo, for 230 patients aged 5 to 58 years of age with sickle cell disease. Endari™ was approved in July 2017 by the US Food and Drug Administration based on the safety and efficacy data from this study. Glutamine is an amino acid that is involved in several biochemical reactions.

The study showed that whether administered alone or with hydroxyurea, L-glutamine reduced the frequency of sickle cell pain crises by 25% and four in the placebo group) and hospitalizations by 33% (a median of two hospitalizations in the L-glutamine group and three in the placebo group). Additional findings showed lower cumulative hospital days of 41% and a lower incidence of dangerous acute chest syndrome (ACS) by more than 60 percent.

“This study validated research on the safety of pharmaceutical grade L-glutamine which has antioxidant properties that improves the NAD redox potential in sickle cell patients. Safe neutraceuticals are of major importance to the sickle cell community,” said Elliott Vichinsky, MD, Director of Hematology/Oncology at the Northern California Sickle Center at UCSF Benioff Children’s Hospital Oakland. “Our clinical trial found that L-glutamine, which does not require any routine laboratory monitoring, decreases pain events in patients by itself or in combination with hydroxyurea. It is a major advance in therapy for sickle cell disease and offers families safe, new therapeutic options.”

SCD is a genetic blood disorder that causes a distortion in the shape of red blood cells. This leads to the many symptoms and medical problems affecting children and adults with SCD, including pain, anemia, and bone, kidney, lung and neurologic problems.

“Endari, is the first approved treatment for SCD in pediatric patients 5 years of age and older and the first in nearly 20 years for adults,” said study co-author Yutaka Niihara, MD, CEO and founder of Emmaus, which produces the product. “Our hope in sharing the results of this data from the New England Journal of Medicine is to increase awareness of SCD, a lifelong hereditary blood disorder which commonly affects those of African descent, as well those from Central and South America and people of Middle Eastern, Asian, Indian and Mediterranean descent. It is important for patients to know that they have a treatment option for this debilitating disease.”

The double-blind trial evaluated the efficacy and safety of pharmaceutical-grade L-glutamine administered twice daily by mouth, as compared with placebo, in reducing the frequency of pain crises among patients with sickle cell anemia or sickle β0-thalassemia and 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 continued that therapy through the 48-week treatment period.

Patients were randomly assigned, in a 2:1 ratio, to receive L-glutamine (152 patients) or placebo (78 patients). Those in the L-glutamine group had significantly fewer pain crises than those in the placebo group (P=0.005) and fewer hospitalizations (P=0.005). Approximately 54% of the patients were female and 66% of the patients in both trial groups were already receiving hydroxyurea. The study found that low-grade nausea, non-cardiac chest pain, fatigue and musculoskeletal pain occurred more frequently in the L-glutamine group than in the placebo group.

Funding for this trial was provided by Emmaus Life Sciences, Inc.