News Hour:
Sanofi announced the presentation of the results of the pivotal Phase 3 LixiLan-O and LixiLan-L clinical trials with the investigational titratable fixed-ratio combination of basal insulin glargine 100 Units/mL and GLP-1 receptor agonist lixisenatide in adults with type 2 diabetes. Both studies met their primary endpoints, demonstrating statistically superior reduction of HbA1c (average blood glucose over the previous three months) with the titratable fixed-ratio combination versus comparators (lixisenatide and insulin glargine 100 Units/mL, respectively). The most frequent adverse events were nausea, vomiting and diarrhea.
Full results were presented on June 12 at the American Diabetes Association 76thScientific Sessions in New Orleans, LA, U.S. Top-line results were previously reported in Q3 of 2015.
“These studies reflect Sanofi’s commitment to innovative approaches in developing medicines intended to help patients meet their needs throughout their diabetes journey,” said Jorge Insuasty MD, Senior Vice President, Global Head of Development, Sanofi. “We look forward to continuing to work with the FDA and EMA as they complete their reviews and to receiving their decisions.”
The results of the LixiLan-O and LixiLan-L studies have been included in regulatory submissions to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), with regulatory decisions anticipated in August 2016 (FDA) and Q1 2017 (EMA).
The presentation abstracts are titled:
The proprietary name for the titratable fixed-ratio combination is under consideration. Its safety and efficacy have not been evaluated by any regulatory authority.
Results of Analyses
LixiLan-O
LixiLan-O investigated the efficacy and safety of a once-daily single injection of the titratable fixed-ratio combination of insulin glargine 100 Units/mL and lixisenatide versus treatment with either lixisenatide or insulin glargine 100 Units/mL alone over a 30 week period in 1,170 patients whose type 2 diabetes was not adequately controlled on metformin alone or on metformin combined with a second oral anti-diabetic agent. Treatment with metformin was continued for all participants throughout the study while other oral agents were discontinued.
After 30 weeks, the titratable fixed-ratio combination showed significantly greater reductions in HbA1c from baseline (8.1%) versus insulin glargine 100 Units/mL and lixisenatide (-1.6%, -1.3%, -0.9%, respectively; p<0.0001), reaching mean HbA1c levels of 6.5%, 6.8%, 7.3%, respectively. More subjects reached target HbA1c <7% with the titratable fixed-ratio combination (74%) versus insulin glargine 100 Units/mL (59%) or lixisenatide (33%). Mean body weight increased with insulin glargine 100 Units/mL (+1.1kg), and decreased with the titratable fixed-ratio combination (-0.3kg; difference 1.4kg, p<0.0001) and lixisenatide (-2.3kg).
Documented (≤70 mg/dL) symptomatic hypoglycemia was similar with the titratable fixed-ratio combination (25.6% of patients; 1.44 events/year; E/Y) and insulin glargine 100 Units/mL (23.6% of patients; 1.22 E/Y), but lower with lixisenatide (6.4% of patients; 0.34 E/Y). With the titratable fixed-ratio combination, 9.6% of participants experienced nausea and 3.2% experienced vomiting; with insulin glargine 100 Units/mL, 3.6% of participants experienced nausea and 1.5% experienced vomiting; and with lixisenatide 24.0% of participants experienced nausea and 6.4% experienced vomiting.
LixiLan-L
LixiLan-L investigated the efficacy and safety of the titratable fixed-ratio combination of insulin glargine 100 Units/mL and lixisenatide versus treatment with insulin glargine 100 Units/mL over a 30 week period in 736 patients whose type 2 diabetes was not adequately controlled at screening on basal insulin, alone or combined with one to two oral anti-diabetic agents. Treatment with metformin, if previously taken, was continued throughout the study while other oral agents were discontinued.
After 30 weeks, the titratable fixed-ratio combination showed significantly greater reductions in HbA1c from baseline (8.1%) versus insulin glargine 100 Units/mL (-1.1% versus -0.6%; p<0.0001), reaching mean HbA1c levels of 6.9% and 7.5%, respectively. More subjects reached target HbA1c <7% with the titratable fixed-ratio combination (55%) versus insulin glargine 100 Units/mL (30%; p<0.0001). Mean body weight increased with insulin glargine 100 Units/mL (+0.7 kg), and decreased with the titratable fixed-ratio combination (-0.7 kg; difference 1.4 kg, p<0.0001).
Documented (≤70 mg/dL) symptomatic hypoglycemia was similar with the titratable fixed-ratio combination (40% of patients; 3.0 events/year; E/Y) and insulin glargine 100 Units/mL (42.5% of patients; 4.2 E/Y). With the titratable fixed-ratio combination, 10.4% of participants experienced nausea, and 3.6% experienced vomiting; while with insulin glargine 100 Units/mL 0.5% of participants experienced nausea and 0.5% experienced vomiting.
What is Lantus® (insulin glargine injection) 100 Units/mL?
Prescription Lantus is a long-acting insulin used to treat adults with type 2 diabetes and adults and pediatric patients (children 6 years and older) with type 1 diabetes for the control of high blood sugar.
Important Safety Information For Lantus (insulin glargine injection) 100 Units/mL
Do not take Lantus during episodes of low blood sugar or if you are allergic to insulin or any of the inactive ingredients in Lantus.
Do not share needles, insulin pens, or syringes with others. Do NOT reuse needles.
Before starting Lantus, tell your doctor about all your medical conditions, including if you have liver or kidney problems, if you are pregnant or planning to become pregnant or if you are breast-feeding or planning to breast-feed.
Heart failure can occur if you are taking insulin together with certain medicines called TZDs (thiazolidinediones), even if you have never had heart failure or other heart problems. If you already have heart failure, it may get worse while you take TZDs with Lantus. Your treatment with TZDs and Lantus may need to be changed or stopped by your doctor if you have new or worsening heart failure. Tell your doctor if you have any new or worsening symptoms of heart failure, including:
Tell your doctor about all the medications you take, including OTC medicines, vitamins, and supplements, including herbal supplements.
Lantus should be taken once a day at the same time every day. Test your blood sugar levels while using insulin, such as Lantus. Do not make any changes to your dose or type of insulin without talking to your healthcare provider. Any change of insulin should be made cautiously and only under medical supervision.
Do NOT dilute or mix Lantus with any other insulin or solution. It will not work as intended and you may lose blood sugar control, which could be serious. Lantus must only be used if the solution is clear and colorless with no particles visible. Always make sure you have the correct insulin before each injection.
While using Lantus, do not drive or operate heavy machinery until you know how Lantus affects you. You should not drink alcohol or use other medicines that contain alcohol.
The most common side effect of insulin, including Lantus, is low blood sugar (hypoglycemia), which may be serious and life threatening. It may cause harm to your heart or brain. Symptoms of serious low blood sugar may include shaking, sweating, fast heartbeat, and blurred vision.
Lantus may cause serious side effects that can lead to death, such as severe allergic reactions. Get medical help right away if you have:
Other possible side effects may include swelling, weight gain, low potassium levels, injection site reactions, including changes in fat tissue at the injection site, and allergic reactions.
