Immunoglobulin G1, anti-(human neural apoptosis-regulated proteinase 1) (human REGN727 heavy chain), disulfide with human REGN727 κ-chain, dimer
Immunoglobulin G1, anti-(human proprotein convertase subtilisin/kexin type 9
(EC=3.4.21.-, neural apoptosis-regulated convertase 1, proprotein convertase 9,
subtilisin/kexin-like protease PC9)); human monoclonal REGN727 des-448-
lysine(CH3-K107)-1 heavy chain (221-220′)-disulfide with human monoclonal
REGN727 light chain dimer (227-227”:230-230”)-bisdisulfide
Clinical Trials for Compound
|Number of clinical trials registered at clinicaltrials.gov||30|
|Alirocumab heavy chain||EVQLVESGGGLVQPGGSLRLSCAASGFTFNNYAMNWVRQAPGKGLDWVSTISGSGGTTNY ADSVKGRFIISRDSSKHTLYLQMNSLRAEDTAVYYCAKDSNWGNFDLWGRGTLVTVSSAS TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPG|
|Alirocumab light chain||DIVMTQSPDSLAVSLGERATINCKSSQSVLYRSNNRNFLGWYQQKPGQPPNLLIYWASTR ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTPYTFGQGTKLEIKRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC|
When the results from Phase II trials of Sanofi and Regeneron’s proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor alirocumab were presented in March, they stunned even the company representatives working on the trials. “I’m still amazed by the reduction in low-density lipoprotein cholesterol (LDL-C) that we saw with our drug,” says Bill Sasiela, vice president of cardiovascular and metabolic research at Regeneron. The monoclonal antibody (mAb) reduced LDL-C levels by up to 73% in three mid-stage trials, irrespective of baseline LDL-C levels or background treatment, offering hope for millions of patients who can’t hit the recommended cholesterol targets with statins — the standard therapies for lowering LDL-C levels in patients with cardiovascular disease. Spurred on by these results, Sanofi and Regeneron geared up into Phase III trials of the first-in-class alirocumab (also known as REGN727 and SAR236553) over the summer, and initiated the latest and largest trial — an 18,000-patient outcomes study
It is a Proprotein convertase subtilisin/kexin type 9, (also known as PCSK9) inhibitor . Phase III trials showed a 47% reduction in LDL-C. There was a high rate of adverse events with 69% experiencing side effects (most common problem was infection).
About PCSK9 PCSK9 is known to be a determinant of circulating LDL levels, as it binds to LDL receptors resulting in their degradation so that fewer are available on liver cells to remove excess LDL-cholesterol from the blood. Moreover, traditional LDL-lowering therapies such as statins actually stimulate the production of PCSK9, which limits their own ability to lower LDL-cholesterol. Blocking the PCSK9 pathway is therefore a potentially novel mechanism for lowering LDL-cholesterol.
Alirocumab is an investigational, fully-human monoclonal antibody that targets and blocks PCSK9. It is administered via subcutaneous injection. By inhibiting PCSK9, a determinant of circulating LDL-C levels in the blood, alirocumab has been shown in pre-clinical studies to increase the number of LDL receptors on hepatocytes, thereby lowering LDL-C.
The investigational agent described above is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority
- Statement On A Nonproprietary Name Adopted By The USAN Council – Alirocumab, American Medical Association.
PARIS and TARRYTOWN, N.Y., Oct. 16, 2013 /PRNewswire via COMTEX/ — Sanofi and Regeneron Pharmaceuticals, Inc. REGN -1.73% today announced that the Phase 3 ODYSSEY MONO trial with alirocumab, an investigational monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9), met its primary efficacy endpoint. The mean low-density lipoprotein-cholesterol (LDL-C, or “bad” cholesterol) reduction from baseline to week 24, the primary efficacy endpoint of the study, was significantly greater in patients randomized to alirocumab, as compared to patients randomized to ezetimibe (47.2% vs. 15.6%, p<0.0001). In the trial, which employed a dose increase (up-titration) for patients who did not achieve an LDL-C level of 70 milligrams/deciliter (mg/dL), the majority of patients remained on the initial low dose of alirocumab of 75 milligrams (mg). read at
Pipeline of selected PCSK9 inhibitors
|Drug name||Companies||Modality||Clinical phase|
|Alirocumab (also known as REGN727 and SAR236553)||Regeneron/Sanofi||Monoclonal antibody||III|
|PCSK9, proprotein convertase subtilisin kexin 9.|