| Primary information |
|---|
| ThPP ID | Th1162 |
| Therapeutic Peptide/Protein Name | Alirocumab |
| Sequence | NA view full sequnce in fasta |
| Functional Classification | Ic |
| Molecular Weight | 146001 |
| Chemical Formula | C6472H9996N1736O2032S43 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting Point (℃) | NA |
| Half Life | In monotherapy, the median half-life of alirocumab at steady state was 17–20 days in patients rece |
| Description | Alirocumab is a biopharmaceutical drug approved by the FDA in July 2015 as a second line treatment for high cholesterol for adults whose LDL-cholesterol (LDL-C) is not controlled by diet and statin treatment. It is a human monoclonal antibody administered by subcutaneous injection that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. PCSK9 inhibition facilitates more LDL-C clearance from the blood. |
| Indication/Disease | Alirocumab is indicated as an adjunct to diet and maximally tolerated statin therapy in adults who require additional LDL-cholesterol (LDL-C) lowering due to heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease. |
| Pharmacodynamics | Alirocumab reduces levels of PCSK9 in a concentration-dependent manner. |
| Mechanism of Action | Alirocumab is a fully human IgG1 monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have gain of function mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease. |
| Toxicity | During a 13-week toxicology study of 75 mg/kg once weekly alirocumab in combination with 40 mg/kg once daily atorvastatin in adult monkeys, there were no effects of PRALUENT on the humoral immune response to keyhole limpet hemocyanin (KLH) after one to two months at exposures 100-fold greater than the exposure at the maximum recommended human dose of 150 mg every two weeks, based on AUC. |
| Metabolism | Antibodies are generally metabolized by the reticuloendothelial system and degraded into small peptides and individual amino acids - therefore specific metabolism studies were not conducted. Alirocumab did not show evidence of affecting CYP 450 enzymes or transporter proteins in co-administration with statins. |
| Absorption | Following subcutaneous (SC) administration, alirocumab is absorbed into the bloodstream and maximum concentrations are reached at a median time of 3-7 days. The absolute availability after SC administration was 85%. |
| Volume of Distribution | Alirocumab is mainly distributed through the circulatory system, with minimal extravascular distribution. |
| Clearance | N.A. |
| Categories | N.A. |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | The risk or severity of adverse effects can be increased when Alirocumab is combined with Belimumab. |
| Target | Proprotein convertase subtilisin/kexin type 10 |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Praluent |
| Company | Sanofi Aventis Canada Inc |
| Brand Discription | PRALUENT is a sterile, preservative-free, clear, colorless to pale yellow solution for subcutaneous injection. PRALUENT 75 mg/mL or 150 mg/mL solution for subcutaneous injection in a single-dose pre-filled pen or single-dose pre-filled syringe is supplied in a siliconized 1 mL Type-1 clear glass syringe. The needle shield is not made with natural rubber latex. |
| Prescribed for | It is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C. |
| Chemical Name | NA |
| Formulation | 150 mg |
| Physcial Appearnce | solution |
| Route of Administration | Subcutaneous |
| Recommended Dosage | The recommended starting dose of PRALUENT is 75 mg administered subcutaneously once every 2 weeks, since the majority of patients achieve sufficient LDL-C reduction with this dosage. If the LDL-C response is inadequate, the dosage may be increased to the maximum dosage of 150 mg administered every 2 weeks. |
| Contraindication | It is contraindicated in patients with a history of a serious hypersensitivity reaction to PRALUENT. Reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization. |
| Side Effects | Allergic Reactions |
| Useful Link | http://www.rxlist.com/praluent-drug/clinical-pharmacology.htm |
| PubMed ID | 27729681, 26651519, 25484055, 24284914, 23254906, 25484055, 24284914, 23254906, 25609019 |
| 3-D Structure | N.A. |