Cerenis Therapeutics, the biopharmaceutical company developing CER-001, an engineered human apoA-I-containing pre-beta HDL mimetic, for the treatment of cardiovascular disease, announced today that it has received two separate Orphan Drug Designations from the European Medicines Agency (EMA) for the use of CER-001 in the treatment of patients with rare genetic defects in HDL synthesis/maturation pathways, specifically apoA-I deficiency and ABCA1 deficiency.
Inherited defects in the apoA-I gene or the ABCA1 gene in both homozygous and heterozygous forms can act in a dominant manner to cause Familial Primary HypoAlphalipoproteinemia (FPHA), a rare syndrome characterised by the absence of or a severe deficiency of HDL particles in the circulation. Due to either the impaired production/maturation or the premature destruction of HDL particles, the Reverse Lipid Transport (RLT) pathway, the body’s only natural mechanism for the elimination of cholesterol, is compromised. Patients experience a rapid accumulation of cholesterol, particularly in blood vessels, which often results in accelerated atherosclerosis and premature cardiovascular disease.
John J.P. Kastelein, MD, PhD, of the Department of Vascular Medicine at the Academic Medical Center in Amsterdam, The Netherlands, said: “These patients accumulate cholesterol and experience premature cardiovascular events despite essentially ‘normal’ levels of LDL-C or despite having been placed on optimized statin therapy. The mechanism of action of statins does not directly target this pathophysiology in these patients with FPHA; as a result the benefit derived from statins will be at best indirect and incomplete. There is no treatment currently available which can directly restore normal HDL levels or normal levels of apoA-I.”
Proof-of-mechanism data supporting the orphan designation application were obtained from the SAMBA Phase II efficacy and safety trial of CER-001 in patients with FPHA and were presented at the European Atherosclerosis Society in June 2014. The data from this trial showed that CER-001 reconstituted the RLT pathway in individuals who have defects in the natural HDL pathway and facilitated elimination of cholesterol from the body. The results of these two studies support the future use of CER-001 for chronic administration aiming to reduce the elevated cardiovascular risk in low HDL patients with a high unmet clinical need.
John F. Paolini, MD, PhD, FACC, Chief Medical Officer of Cerenis, said, “CER-001 has now been shown in Phase II trials to provide benefit to patients suffering from accelerated cardiovascular disease caused by genetic defects at both ends of the spectrum of cholesterol homeostasis. The product has a good safety profile as observed in all studies performed thus far.”
Jean-Louis Dasseux, PhD, MBA, and Chief Executive Officer of Cerenis, concluded: “CER-001 has the potential to be an important therapy not only for patients with rare diseases, such as FPHA, for which there is currently no other therapeutic option, but also for larger patient populations such as post-ACS patients. These two orphan drug designations from the EMA validate our approach and will enable us to accelerate the development of CER-001 and provide this new treatment option to patients.”