Sanofi Races to Help Hypercholesterolemia Patients Meet their LDL-C Goals
A rare gene mutation has become a new target to aid in the fight against high cholesterol. Sanofi is one of the major pharmas that is involved in the race to develop a drug that mimics the effects of the mutation. Associate Web Editor Mia Burns interviewed Dr. Jay Edelberg, head, PCSK9 Development and Launch Unit, Sanofi, about the company’s work in addressing a longstanding health concern.
Q: Is Sanofi working in partnership with Pfizer and Amgen in the gene mutation research?
A: Sanofi engages in several external partnerships in the fast-moving field of translational medicine. We have a very fruitful cooperation with Regeneron, with whom we are developing a number of biologics for a variety of disease targets.
PCSK9, considered as the most promising target in modern medicine, is one of our key focus areas. Our PCSK9-inhibitor alirocumab, is well progressing in its ongoing Phase III clinical development ODYSSEY, which has been ongoing since 2012. The program encompasses over 10 trials and studies alirocumab in people suffering from uncontrolled hypercholesterolemia with and without cardiovascular disease and we plan to report first results later this year.
Q: Could this discovery benefit people who have high cholesterol despite having a good diet and exercising on a regular basis?
A: Yes. Bringing LDL-C to goal is the primary treatment objective in patients with hypercholesterolemia with or without history of cardiovascular disease.
Despite cholesterol-lowering therapy almost two thirds of all adults in the U.S. who are treated do not achieve their LDL-C goal. It is also estimated from NHANES data that 23 percent of high risk patients who are treated do not achieve goal of <100 mg/dL and 76 percent of high risk patients do not achieve LDL-C <70 mg/dL. Approximately 80 percent of patients with heterozygous familial hypercholesterolemia (HeFH) have poorly controlled hypercholesterolemia and do not achieve LDL-C <100 mg/dL.
Should PCSK9-inhibitors be approved, we hope that they will contribute to improving today’s situation for those patients.
Q: For how long has Sanofi been working on a drug that mimics the effects of the gene mutation? What phase is this drug in? In what nations is Sanofi conducting the trials? If the trials are only taking place within one nation at the moment, does Sanofi have plans to initiate clinical trials within other countries?
A: First discovered in 2003, the move from bench to bedside was rapid in the field of PCSK9 inhibition. In 2009 we conducted preclinical work and the first subject was treated with alirocumab early in 2010. In 2012 the very encouraging first Phase 2 results in the field were published for alirocumab, demonstrating that alirocumab can lower LDL-C by about 70 percent on top of statins and bring almost 100 percent of patients to their LDL-C goal with an acceptable safety profile. The Phase III program ODYSSEY started in 2012 and we look forward to reporting first Phase III results later this year.
The ongoing Phase III program ODYSSEY is a world-wide program conducted across North and South America, Europe, Australia, and Asia.
This program with alirocumab will enroll more than 22,000 patients and currently includes 11 clinical trials with alirocumab both in combination with other lipid-lowering agents and as monotherapy. The ODYSSEY program includes the following patient populations: patients with HeFH who are inadequately controlled by current lipid-modifying therapy; patients with primary hypercholesterolemia unable to tolerate statins; and high cardiovascular risk patients with primary hypercholesterolemia. These patient populations with uncontrolled hypercholesterolemia would particularly benefit from improved treatments to reduce their cardiovascular risk. The ODYSSEY program includes the following trials:
•ODYSSEY MONO: The primary objective of this study was to demonstrate the safety and efficacy of alirocumab as a monotherapy in patients with primary hypercholesterolemia. All patients will be treated for six months.
•ODYSSEY FH I, FH2, and HIGH FH: These three studies evaluate alirocumab as an add-on treatment in patients with HeFH who are not adequately controlled with their current lipid-modifying therapy. All patients will be treated for 18 months.
•ODYSSEY COMBO I and COMBO II: These two studies evaluate alirocumab as an add-on therapy in patients with primary hypercholesterolemia and at high cardiovascular risk and not adequately controlled with their lipid-modifying therapy. Patients in the COMBO I study will be treated for one year, while patients in the COMBO II study will be treated for two years.
•ODYSSEY ALTERNATIVE: The primary objective of this study is to demonstrate the safety and efficacy of alirocumab in comparison with ezetimibe in patients with primary hypercholesterolemia unable to tolerate statins. Patients in this study will be treated for 18 months.
•ODYSSEY OPTIONS I and OPTIONS II: The primary objective of these studies is to assess the efficacy and safety of alirocumab as an add-on in patients with primary hypercholesterolemia at high cardiovascular risk or with HeFH who are not adequately controlled on statins, in comparison to several other lipid-lowering strategies. The duration for both studies will be six months.
•ODYSSEY LONG TERM: This study will evaluate the long-term safety and tolerability of alirocumab in patients with hypercholesterolemia at high cardiovascular risk or patients with HeFH inadequately controlled with their current lipid-modifying therapy. All patients will be treated for 18 months.
•ODYSSEY OUTCOMES: The primary objective of this study is to compare the effect of alirocumab with placebo on the occurrence of cardiovascular events (composite endpoint of coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), fatal and non-fatal ischemic stroke, unstable angina requiring hospitalization) in patients who have experienced a recent acute coronary syndrome (ACS) event.
We thank investigators from over 2000 centers and the patients who are contributing to our late stage development program with alirocumab.
Q: What details can you share about the Sanofi drug candidates within this category? Are they biologics? Are Sanofi researchers taking cost into account as biologics are known to be expensive?
A: Alirocumab is a biologic. It is delivered in a 1 mL self-administration auto-injector. Economic aspects are an integral part of our development strategy and we aim at delivering cost effective solutions to payers and patients.
Q: What else can you share about the deeper background of this unique science?
A: PCSK9 was discovered less than a decade ago in a family with autosomal dominant hypercholesterolemia and premature cardiovascular disease. Mechanistically, PCSK9 down regulates the density of LDL receptors on the surface of hepatocytes. With too few LDL receptors, LDL-C uptake by the liver is reduced and hypercholesterolemia may develop which in turn can increase the risk of cardiovascular disease. Our PCSK9-inhibitor research aims at bringing people living with uncontrolled LDL-C to goal, reducing their risk of heart disease. We are excited to potentially address a relevant unmet medical need offering patients an option that may be complementary to currently existing therapies. We look forward to reporting first results from our ongoing global Phase III program ODYSSEY later this year.
Posted: July 2013