Branded products in diabetes care commercialized by Sanofi under an exclusive worldwide license.
Zealand's first invented medicine, lixisenatide, a once-daily prandial GLP-1 receptor agonist for the treatment of type 2 diabetes, is licensed to Sanofi.
Lixisenatide is available as Adlyxin® in the U.S. and is approved as Lyxumia® in more than 60 countries worldwide and marketed in over 40 by Sanofi. Commercial launches include most EU countries, Japan, Brazil, Mexico, India and the U.S. as of January 2017. Adlyxin®/Lyxumia® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Soliqua™ 100/33/ Suliqua™
Soliqua™ 100/33 in the U.S.
On 21 November, Sanofi received U.S. Food and Drug Administration (FDA) approval for Soliqua™ 100/33. Launched and available in U.S. retail pharmacies in January 2017.
Soliqua™ 100/33 is a combination of lixisenatide.and insulin glargine
(Lantus®) and a GLP-1 receptor agonist, in a once-daily injection marketed
in the US by Sanofi. This product has been approved in the EU as Suliqua™
for type 2 patients. Soliqua™ 100/33 has been approved in the U.S. indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on basal insulin (with a daily dose range from 15 to 60 Units) or lixisenatide. Soliqua™ 100/33 is marketed in the U.S. by Sanofi.
Soliqua™ 100/33 is delivered in the U.S. in a single pre-filled pen for once-daily
dosing using SoloSTAR® technology, the most frequently used disposable insulin
injection pen in the world.
Suliqua™ in the EU
Suliqua™ was approved in the EU in january 2017 for type 2 patients for use in combination with metformin to improve glycemic control when this has not been provided by metformin alone or metformin combined with another oral glucose
lowering medicinal product or with basal insulin. Suliqua™ will be marketed in the
EU by Sanofi.
Suliqua™ will be delivered in two prefilled SoloSTAR® pens, providing different
dosing options that may help answer individual market and patient insulin
License collaboration with Sanofi
• The contract with Sanofi includes the GLP-1 receptor agonist lixisenatide and any combination product
• Zealand pays 13,5% of its incoming revenue on all lixisenatide products to third parties
• The patent expires on different dates in different countries, but in most cases it is in 2025 (No WO 01/04156. The US No is US RE45,313 and the EU No is EP 1196444).
In an international Phase II trial, GetGoal, which included 11 clinical studies involving more than 5,000 patients with Type 2 diabetes, lixisenatide has shown to have a similar effect on glucose reduction with advantages on body weight compared to rapid-acting insulin, when added to basal insulin for treatment intensification in patients with Type 2 diabetes. The results establish the product as the first once-daily prandial GLP-1 receptor agonist, characterized by a pronounced lowering effect on post-prandial glucose (PPG) contributing to HbA1c reduction, a beneficial effect on body weight, and a limited risk of hypoglycemia. The PPG-lowering effect of lixisenatide complements the predominantly fasting plasma glucose (FPG)-lowering effect of basal insulin, making Lyxumia® particularly relevant as an add-on therapy to basal insulin, including Lantus®, to better control blood sugar.
Intense – “real-world” observational study of lyxumia® initiated in Europe
Sanofi has initiated the INTENSE (Intensifying iNsulin Therapy in type 2 diabetes: lixisENatide or Standard of carE) trial, a new patient-centric non-interventional study of Lyxumia® compared to other forms of injectable insulin intensification therapies, including short acting insulin. INTENSE, which is being initiated in several European countries, has a prospective recruitment of 2,400 adults with Type 2 diabetes, and will assess the safety and efficacy of adding injectable therapies to basal insulin, as well as the factors predicting the effectiveness of this intensification of treatment in a real-world standard of care setting.
INTENSE will follow patients to also examine the ways real-life circumstances can impact patients’ perceptions, their ability to manage diabetes and their adherence to treatment. The first participant in this large-scale, post-approval observational study was enrolled at the end of July 2014 at Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas, Gran Canaria, Spain.
Elixa – study establishes cardiovascular safety profile of lixisenatide
In June 2015, at the American Diabetes Association (ADA) 75th Scientific Sessions in Boston, Sanofi presented full results of ELIXA, a Phase IIIb cardiovascular safety outcomes trial of lixisenatide (Lyxumia®/Adlyxin™) compared to placebo in a cardiovascular high-risk population of adults with Type 2 diabetes. The results demonstrated lixisenatide to be safe versus placebo on all cardiovascular safety parameters and the outcome establishes lixisenatide as the first glucacon-like peptide-1 receptor agonist (GLP-1 RA) with proven cardiovascular safety.
The results from ELIXA showed that lixisenatide was non-inferior, although not superior, to placebo for cardiovascular safety, and demonstrate that there is no additional cardiovascular risk, in a high-risk patient population, associated with treatment with lixisenatide. Additional safety findings included no signal for increased risk of heart failure, pancreatitis, pancreatic cancer or severe symptomatic hypoglycemia.
ELIXA is the first event-driven cardiovascular outcomes trial to have provided data for a medicine from the GLP-1 receptor agonist class. The trial was a randomized, double-blind, and parallel group design comparing lixisenatide to placebo in a population of adults with Type 2 diabetes and high cardiovascular risk (patients who have recently experienced a spontaneous acute coronary syndrome event). More than 6,000 patients participated and were treated in the trial. The composite primary endpoint, which was evaluated for non-inferiority and superiority, comprised cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for unstable angina.
The global ELIXA study started in June 2010 and was completed in March 2015.
Pivotal Phase III supportive results
Soliqua™ 100/33 / Suliqua™ was formerly referred to as LixiLan (or iGlarLixi). The Phase III program was therefore conducted with the name LixiLan.
The pivotal Phase III development program for LixiLan was comprised of two trials; LixiLan-O (1,170 adults with Type 2 diabetes) and LixiLan-L (736 adults with Type 2 diabetes). Both trials was completed in 2015.
Results of LixiLan-O
LixiLan-O investigated the efficacy and safety of a once-daily single injection of iGlarLixi, the titratable fixed-ratio combination of Lantus® (insulin glargine 100 Units/mL) and lixisenatide versus treatment with either lixisenatide or Lantus® alone over a 30 week period. The trial included 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, iGlarLixi showed significantly greater reductions in HbA1c from baseline (8.1%) vs Lantus® and lixisenatide (-1.6%, -1.3%, -0.9%, respectively; p<0.0001), with patients reaching mean HbA1c levels of 6.5%, 6.8%, 7.3%, respectively. More patients reached target HbA1c <7% with iGlarLixi (74%) vs Lantus® (59%) or lixisenatide (33%). Mean body weight increased with Lantus® (+1.1kg), and decreased with iGlarLixi (-0.3kg; difference 1.4kg, p<0.0001) and with lixisenatide (-2.3kg).
Documented (≤70 mg/dL) symptomatic hypoglycemia was similar with iGlarLixi (25.6% of patients; 1.44 events/year (E/Y)) and Lantus® (23.6% of patients; 1.22 E/Y), but lower with lixisenatide (6.4% of patients; 0.34 E/Y). With iGlarLixi, 9.6% of participants experienced nausea and 3.2% experienced vomiting; with Lantus®, 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.
Results of LixiLan-L
LixiLan-L investigated the efficacy and safety of a once-daily single injection of iGlarLixi, the titratable fixed-ratio combination of Lantus® (insulin glargine 100 Units/mL) and lixisenatide versus treatment with Lantus® over a 30 week period. The trial included 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, iGlarLixi showed significantly greater reductions in HbA1c from baseline (8.1%) versus Lantus® (-1.1% vs. -0.6%; p<0.0001), with patients reaching mean HbA1c levels of 6.9% and 7.5%, respectively. More patients reached target HbA1c <7% with iGlarLixi (55%) versus Lantus® (30%; p<0.0001). Mean body weight increased with Lantus® (+0.7 kg), and decreased with iGlarLixi (-0.7 kg; difference 1.4 kg, p<0.0001).
Documented (≤70 mg/dL) symptomatic hypoglycemia was similar with iGlarLixi (40% of patients; 3.0 events/year (E/Y)) and Lantus® (42.5% of patients; 4.2 E/Y). With iGlarLixi, 10.4% of participants experienced nausea, and 3.6% experienced vomiting; while with Lantus® 0.5% of participants experienced nausea and 0.5% experienced vomiting.
Results from a clinical phase iib trial of lixilan
Sanofi has evaluated LixiLan in a Phase IIb trial involving 323 patients with Type 2 diabetes insufficiently controlled on oral anti-diabetes medication (OADs) and with insulin glargine (Lantus®) as an active comparator.
Results from the Phase IIb trial were presented at both ADA 2014 and ADA 2015. In the trial, LixiLan (a fixed-ratio single-injection combination of lixisenatide and insulin glargine (Lantus®) (2 units glargine/1 mcg lixisenatide) gave a robust HbA1c reduction with weight loss and no increased hypoglycemia versus Lantus® and with very low gastro-intestinal adverse events in Type 2 diabetes patients inadequately controlled on metformin.
Results from Phase IIb trial showed a HbA1c lowering to 6.3 % and a weight loos of 1.2 kg for patients insufficiently controlled on insulin. Moreover, results showed no additional incidences of hypoglycemia compared to Lantus® as well as less frequent nausea and vomiting compared to what has been reported for the GLP-1 rapid acting class.