Short- to mid-term value driversLyxumia® and the Lantus®/Lyxumia® combination product
Global roll-out of Lyxumia® as a new treatment of Type 2 diabetes is expected to lead to increasing royalty revenues to Zealand in the coming years. Regulatory filing in the US is expected in 2015.
The fixed-ratio combination of Lyxumia® with Lantus®, the most prescribed basal insulin world-wide, in a single daily injection was advanced into pivotal Phase III development by Sanofi in early 2014. The program is expected to complete in the 2nd half of 2015, and regulatory submissions could begin as early as the end of 2015.
Lyxumia® – Once-daily prandial GLP-1 receptor agonist for Type 2 diabetes, invented by Zealand and marketed by Sanofi
In March 2013, Lyxumia® was launched in the first markets by Sanofi, who holds global development and commercial rights to the product under a license agreement with Zealand. Lyxumia® is currently approved in over 40 countries worldwide for the treatment of Type 2 diabetes, with commercial launches ongoing in Europe, Japan, Mexico and other markets.
Zealand is entitled to royalties based on Sanofi’s global sales of Lyxumia®.
In 2013, initial royalty revenue amounted to EUR 0.9 million (DKK 6.5 million), and Sanofi continues the commercial roll-out of the product.
Expected benefits on fasting and post-prandial glucose
Treatment wiih basal insulin, is effective in controlling blood sugar, mainly via effect on fasting (in between meals) glucose levels. Basal insulin is however, not very effective on meal related glucose peaks, also referred to as post-prandial glucose (PPG).
Adding a GLP-1 agonist with pronounced effect on PPG complements basal insulin in normalizing blood sugar levels over the course of the day.
Lyxumia®’s profile makes it particularly well suited for use as add-on to basal insulin, incl. Lantus®
Lyxumia®(lixisenatide) is associated with a significant lowering of HbA1C (glycosylated hemoglobin), a beneficial effect on body weight and a predominant effect on lowering meal related glucose (post-prandial glucose, PPG). This profile makes Lyxumia® particularly well suited for use as add-on therapy to basal insulin, including Lantus® (insulin glargine). Lantus® is Sanofi’s leading diabetes product and the most prescribed basal insulin world-wide with annual sales of EUR 5.7 billion in 2013.
In February 2013, FDA accepted a New Drug Application (NDA) filed by Sanofi for lixisenatide in the US. The filing included interim results from the ongoing cardio-vascular outcome study on lixisenatide, ELIXA.
In September, Sanofi announced its decision to withdraw the application and instead plan for resubmission in 2015, after completion of the ELIXA CV study.
The decision to withdraw the lixisenatide application followed discussions with the FDA regarding its proposed process for the review of interim data. Sanofi believes that potential public disclosure of early interim data, even with safeguards, could potentially compromise the integrity of the ongoing ELIXA study. Sanofi’s decision was not related to safety issues or deficiencies in the NDA.
ELIXA – Lyxumia® (lixisenatide) CV outcome study: Completion in 2015
Filing for submission of lixisenatide in the US is expected in 2015 after completion of the ELIXA CV safety study
The evaluation of lixisenatide in acute coronary syndrome (ELIXA) study is an eventdriven cardiovascular (CV) outcome study in Type 2 diabetic patients with high CV risk.
The primary objective of the ELIXA study is to demonstrate that lixisenatide can reduce CV morbidity and mortality (composite endpoint of CV death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina) compared to placebo in Type 2 diabetic patients who recently experienced an acute coronary syndrome (ACS) event.
The ELIXA study started in June 2010 with a target enrollment of 6,000 patients. As of August, 2013, the study was fully enrolled and study completion is expected in 2015, with results available that same year.
The fixed-ratio single injection combination of Lyxumia® with Lantus® – LixiLan Phase III development program started by Sanofi in early 2014
The fixed-ratio combination has been evaluated by Sanofi in a Phase IIb study versus Lantus® alone for its effect on glycemic control, as measured by HbA1c reduction over 24 weeks, in 323 Type 2 diabetic patients treated with metformin. The study was completed in 2013 and publication of the results is expected in connection with a medical congress later in 2014.The fixed-ratio combination of Lyxumia® (lixisenatide) and Lantus® (insulin glargine) is administered as a single daily injection.
In February 2014, Sanofi announced the initiation of the LixiLan Phase III clinical development program for the fixed-ratio combination.
The LixiLan program comprises two studies:
- LixiLan-O (O = Oral) is investigating the effect of treatment with the fixed-ratio combination of Lyxumia® and Lantus® in people with Type 2 diabetes (1,125 patients) versus treatment with either Lantus® or Lyxumia® alone. The first patient was screened for this study in February 2014.
- LixiLan-L (L = Lantus) is investigating the effect of treatment with the fixed-ratio combination of Lyxumia® and Lantus® on HbA1c levels in people with Type 2 diabetes (700 patients) versus treatment with Lantus® alone. The first patient was screened for this study at the end of January 2014.
Completion of the LixiLan studies is expected in the 2nd half of 2015 and the planned timing for regulatory filings leaves the potential for the fixed-ratio combination of Lyxumia® and Lantus® to be the first fixed-ratio combination of a basal insulin with a GLP-1 agonist in a single daily injection to be marketed in the US.
Lyxumia® (lixisenatide) and Lantus®/Lyxumia® combination product – Development timeline
Zealand invents lixisenatide