Endari (L-glutamine) / Emmaus - LARVOL DELTA

Effects of L-Glutamine on Biomarkers of Response in Sickle Cell Disease: A Pharmacokinetics-Pharmacodynamics Analysis (ASH 2023) - P4 | "Oral L-glutamine (Endari®) has been approved by the US-FDA to reduce the acute complications of sickle cell disease (SCD) in patients at least 5 years of age...This PK-PD analysis of L-glutamine reveals biological effects that alter RBC characteristics and could modify SCD-related complications, with a complex interplay summarized in Figure 1. Prospective studies can validate these biomarkers and be used to monitor the effects of L-glutamine therapy in SCD patients."

Biomarker • PK/PD data • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

Trial of First-line L-glutamine With Gemcitabine and Nab-paclitaxel in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Jun Gong, MD | Active, not recruiting ➔ Completed

Trial completion • Oncology • Pancreatic Cancer • Solid Tumor

Real-World Experience of L-Glutamine in Sickle Cell Disease: A Retrospective Observational Study. (PubMed, Pharmacy (Basel)) - "This retrospective observational study evaluated the real-world effectiveness of L-glutamine (Endari®) in reducing SCD-related complications in the Saudi population, where data remain limited...Fifteen patients (median age 12 years, 53% female) met the inclusion criteria; all were on maximum tolerated hydroxyurea...Given the small sample size and limited statistical power, the findings are exploratory. Larger, well-powered, multicenter studies are needed to confirm L-glutamine's potential benefits in this population."

Journal • Observational data • Real-world evidence • Retrospective data • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

REAL-WORLD ASSESSMENT AND CLINICAL VALIDATION OF RED BLOOD CELL (RBC) HEALTH BIOMARKERS IN SICKLE CELL DISEASE (SCD) (EHA 2024) - "The number of blood samples tested in patients receivingSCD-modifying therapies includes the following: hydroxyurea (n=3020), adakveo (n=1240), voxelotor (n=259),and endari (n=289). This report validates that careful coordination with our clinical send-out sites can facilitate successful sampleacquisition, shipping, and processing samples in a central lab setting. Most (50. 1%) testing was indicated tomonitor patients on therapy and a 132% increase since our last report compared to a 24% increase in testingto assess RBC health at baseline or during acute crisis."

Biomarker • Clinical • Real-world • Real-world evidence • Fatigue • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

Patient Demographic and Clinical Characteristics Associated With the Use of the Newly Approved Disease-Modifying Medications for Sickle Cell Disease (ISPOR 2024) - "OBJECTIVES: Endari (L-glutamine), Adakveo (crizanlizumab-tmca), and Oxbryta (voxelotor) are newly approved disease-modifying treatments (DMTs) for sickle cell disease (SCD). At the patient level, the use of the newly approved DMTs was associated with age (being adolescents or young adults) and previous greater healthcare utilization."

Clinical • Genetic Disorders • Hematological Disorders • Oncology • Sickle Cell Disease

Prescribing Trends of Newly Approved Sickle Cell Disease-Modifying Medications (ISPOR 2024) - "The eligible ages for hydroxyurea, Endari, Adakveo, and Oxbryta were 2-64, 5-64, 16-64, and 12-64 years, respectively. Between 2016 and 2021, the dispensing rates for DMTs increased slightly, especially after the approval of Adakveo and Oxbryta. However, the overall dispensing rates of newly approved DMTs remained low."

Genetic Disorders • Hematological Disorders • Oncology • Sickle Cell Disease

Endari treatment ameliorates sickle cell-related disruption in intestinal barrier functions and is associated with prolonged survival in sickle cell mice. (PubMed, Hematology) - "Improved intestinal barrier function was also associated with prolonged survival in Endari-treated SCD mice after repeated experimentally-induced VOC. Our findings provide the evidence supporting the beneficial effects of Enadri in improving intestinal barrier function and associated survival outcomes in SCD."

Journal • Preclinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Casgevy and Lyfgenia: Two gene therapies for sickle cell disease. (PubMed, Med Lett Drugs Ther) - No abstract available

Gene therapy • Journal • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Real-world observational study on the long-term effect of L-glutamine treatment on renal parameters of adult and pediatric patients with sickle cell disease. (PubMed, Front Med (Lausanne)) - "All patients were treated with L-glutamine oral powder (~0.3 g/kg body weight, Endari) twice daily for 120 weeks...This is one of the first studies that assessed the long-term renal outcomes in SCD using L-glutamine. L-glutamine improved the renal function in patients with SCD along with improvements in clinical outcomes and hemolysis, from 48 weeks and sustained through 120 weeks of treatment."

Journal • Observational data • Real-world • Real-world evidence • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

Trial of First-line L-glutamine With Gemcitabine and Nab-paclitaxel in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Jun Gong, MD | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2024 ➔ Jul 2025

Enrollment closed • Trial completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Emmaus Life Sciences Receives Marketing Authorization for Endari in Oman (PRNewswire) - "Emmaus Life Sciences...announced that it has received marketing authorization from the Oman Ministry of Health for the commercial distribution and sale of Endari® (L-glutamine oral powder) in the country to treat sickle cell disease in patients five years of age and older....'We look forward to launching Endari® commercially in Oman and expanding its availability to other countries in the region'."

Non-US regulatory • Anemia • Hematological Disorders • Sickle Cell Disease

RENAL FUNCTIONS EVOLUTION OF 6 SCD PATIENTS TREATED BY L- GLUTAMINE PHARMACEUTICAL GRADE FOR 30 MONTHS: A REAL-WORLD STUDY. (EHA 2023) - "In a Phase 3 clinical trial, L-glutamine demonstrated significant reduction in SCD acute complications with or without hydroxyurea (HU) use, over a 48-week period... Six patients (1 pediatric and 5 adults), with confirmed diagnosis of SCD (HbSS genotype) were treated with L- glutamine oral powder (~0.3 g/kg body weight, Endari®) twice daily for 30 months... This real-world study showed that, along with significant improvement in clinicaloutcomes and hemolysis, L-glutamine improved renal function of six SCD patients after 30 months of treatment. Moreover, this study highlighted that treating SCD patients for 30 months with L-glutamine was safe and did not alter patient renal functions. Sickle cell disease, Hemoglobinopathy, Renal impairment, Hemoglobin"

Clinical • Real-world • Real-world evidence • Genetic Disorders • Hematological Disorders • Pediatrics • Renal Disease • Sickle Cell Disease

L-GLUTAMINE: A NOVEL AND EFFECTIVE THERAPEUTIC TOOL FOR VOC REDUCTION IN SCD (EHA 2023) - "Therapy with L-glutamine (ENDARI) has demonstrated a significant decrease of VOC and acute chest syndrome in a prospective controlled study... Preliminary analysis suggests a decrease in hospitalized VOC under L Glutamine in a real life experience practice.Mechanisms of action of L Glutamine are probably more complex than the effect on the NADH/NAD+ imbalance. Further studies are needed to better understand its role in SCD. Acute chest syndrome, Vasoocclusive crisis, Sickle cell disease, Red blood cell"

Genetic Disorders • Hematological Disorders • Sickle Cell Disease • ANXA5

Emerging Therapies for the Management of Pain and Vaso-Occlusive Crises in Patients With Sickle Cell Disease: A Systematic Review of Randomized Controlled Trials. (PubMed, Cureus) - "Currently, two therapies are approved by the United States Food and Drug Administration (FDA) and are commercially available (crizanlizumab, ADAKVEO and L-glutamine, Endari). While measuring biomarkers may contribute to the understanding of pathophysiology, it does not appear to directly offer predictive value toward treatment success clinically. It can be concluded that there exists a specific opportunity to design, fund, and execute investigations that both compare emerging and existing therapies versus one another and compare combinational therapies versus placebo."

Journal • Review • Genetic Disorders • Hematological Disorders • Infectious Disease • Pain • Sickle Cell Disease

Evaluation of Dosage and Food Effect on L-Glutamine Exposure for Sickle Cell Anemia: A Population Pharmacokinetic Analysis (ASH 2022) - P4 | "Introduction: L-glutamine (Endari®) is an amino acid approved for the treatment of sickle cell disease (SCD)... This is the first report of a population PK analysis of L-glutamine in patients with SCD. We identified that higher baseline glutamine levels and higher doses were associated with lower L-glutamine clearance. In addition, increased doses reduced relative bioavailability, indicating that higher doses (>0.3 g/kg) may not provide higher drug concentrations."

Clinical • PK/PD data • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Pharmacokinetics of L-Glutamine (Endari) in Pediatric and Adult Sickle Cell Disease Patients: A Phase 4, Open-Label, Single-Center Study (ASH 2021) - P4 | "This is the first multi-dose PK study of L-glutamine (Endari) for SCD. Daily dosing was overall well-tolerated, with rapid absorption of 0.1 and 0.3 g/kg doses and no drug accumulation. The highest 0.6 g/kg dose was limited by palatability and featured slower and saturable absorption, so further dose escalation is likely not feasible."

Clinical • P4 data • PK/PD data • Anemia • Dyspepsia • Genetic Disorders • Hematological Disorders • Pain • Pediatrics • Sickle Cell Disease

L-glutamine Treatment in Patients With Diverticulosis (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Emmaus Medical, Inc. | Active, not recruiting ➔ Completed | N=15 ➔ 9

Enrollment change • Trial completion • Gastrointestinal Disorder

Trial of First-line L-glutamine With Gemcitabine and Nab-paclitaxel in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Jun Gong, MD | Trial primary completion date: Dec 2022 ➔ Jun 2023

Metastases • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Real World Applications of Clinical Whole Blood Adhesion (VCAM and P-selectin) Biomarkers in a Pediatric SCD Population (ASH 2022) - "Sixty-two percent of patients were on hydroxyurea (N=68), 4.5% on crizanlizumab (N=5), 5.5% on voxelotor (N=6), and 3% on Endari (N=3). We established preliminary mean values of FA-WB-Psel and FA-WB-VCAM adhesion indices within all SCD genotypes. FA-WB-VCAM was higher in children while FA-WB-Psel was higher in young adults. Our data represents the expected differences in HgbSS and HgbSC phenotypes with patients with HgbSS reflecting higher adhesion values."

Biomarker • Clinical • Real-world evidence • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Immunology • Inflammation • Pain • Pediatrics • Renal Disease • Sickle Cell Disease • VCAM1

Long-Term Efficacy and Safety of L-Glutamine in Preventing Sickle Cell Disease-Related Acute Complications and Hemolysis in Pediatric and Adult Patients: A Real-World Observational Study (ASH 2022) - "Our current real-world observational study is the first to report long term evaluation (120 weeks) of efficacy and safety of L-glutamine (Endari®) therapy in patients living with sickle cell disease in Qatar and French Guiana...Fewer number of patients were taking hydroxyurea at 120 weeks (8 patients) compared to baseline (12 patients)... In this long-term observational study, oral L-glutamine therapy in pediatric and adults living with sickle cell disease resulted in sustained clinical efficacy with improvements in hematologic parameters. L-glutamine therapy was well-tolerated by all patients and there were no safety concerns."

Clinical • Observational data • Real-world evidence • Cardiovascular • Genetic Disorders • Hematological Disorders • Pediatrics • Pulmonary Embolism • Respiratory Diseases • Sickle Cell Disease • Venous Thromboembolism

Trial of First-line L-glutamine With Gemcitabine and Nab-paclitaxel in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Jun Gong, MD | Trial primary completion date: Aug 2022 ➔ Dec 2022

Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Real-World data on efficacy of L-glutamine in preventing sickle cell disease-related complications in pediatric and adult patients. (PubMed, Front Med (Lausanne)) - "The primary objective was to confirm the efficacy of L-glutamine (Endari) therapy in pediatric and adult patients with SCD at follow-up time points of 24, 48 and 72 weeks...No patient reported treatment-related adverse events. Although the sample size was small, our data clearly demonstrated that L-glutamine therapy was safe and significantly improved clinical outcomes and hemolysis parameters in patients with SCD."

Journal • Real-world evidence • Genetic Disorders • Hematological Disorders • Pain • Pediatrics • Sickle Cell Disease

Pharmacokinetics and Safety of Endari (L-glutamine) in Sickle Cell Disease Patients (clinicaltrials.gov) - P4 | N=13 | Completed | Sponsor: Emmaus Medical, Inc. | Recruiting ➔ Completed

Trial completion • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

L-glutamine Treatment in Patients With Diverticulosis (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Emmaus Medical, Inc. | Trial completion date: Jun 2022 ➔ Dec 2022 | Trial primary completion date: May 2022 ➔ Oct 2022

Trial completion date • Trial primary completion date • Gastrointestinal Disorder

L-glutamine to reduce red blood cell sickling and disease severity in sickle cell disease L-glutamine ter vermindering van sikkelen van rode bloedcellen en ziekte-ernst bij sikkelcelziekte (clinicaltrialsregister.eu) - P2 | N=30 | Sponsor: Amsterdam UMC

New P2 trial • Genetic Disorders • Hematological Disorders • Immunology • Inflammation • Sickle Cell Disease