Product
Effient (prasugrel)
Approval Date
July 10, 2009
Release Date
August 2009
Company
Eli Lilly/Daiichi Sankyo
Class
Antithrombotic/thienopyridine/platelet aggregation inhibitor
Indication
Indicated for the reduction of thrombotic cardiovascular events such as stent thrombosis in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI).
Active Ingredient
Prasugrel hydrochloride
Agency Roster
AbelsonTaylor
Marketing Strategy/Execution
Thisapproval was based on results from the TRITON-TIMI 38 clinical trial whichcompared Effient with Plavix (clopidogrel bisulfate tablets, from Bristol-MyersSquibb and Sanofi-Aventis) in reducing cardiovascular events in 13,608 acutecoronary patients managed with PCI. Eli Lilly/Daiichi Sankyo will utilize avariety of channels to communicate the benefits of Effient to physicians,patients and payers.
“Aftermore than a decade of research and testing, we are proud to provide this newtreatment option to patients with ACS who are managed with PCI,” saidTakashi Shoda, president and chief executive officer, Daiichi Sankyo Company,Limited. “Our Daiichi Sankyo and Lilly alliance will launch Effient in theUSin the coming weeks.”Physician Outlook
The approval of Effient (prasugrel), an antiplatelet agent, poses a challenge to market leader Plavix (clopidogrel). Cardiologists are likely to be receptive to Effient use peri-procedurally to PCI based on its superior efficacy vs. clopidogrel, despite its greater bleed risk.
—Mary McBride, Associate Vice President, Research, GfK Healthcare
Also in the Pipeline (courtesy of Adis R&D Insight)
Drug: AngiomaxÂ
Manufacturer: Biogen Idec/CSL
Indication: Acute coronary syndromes
Active ingredient: Bivalirudin
Phase: Launched
Drug: Inegy
Manufacturer: Merck/Schering-Plough Pharmaceuticals
Indication: Acute coronary syndromes
Active ingredient: Ezetimibe/simvastatin
Phase: Launched
Drug: ArixtraÂ
Manufacturer: Sanofi-Aventis/ GlaxoSmithKline
Indication: Acute coronary syndromes
Active ingredient: Fondaparinux sodium
Phase: Launched
Drug: BAY 59-7939
Manufacturer: Bayer/ Johnson & Johnson
Indication: Thromboembolism (Prevention)
Active ingredient: Rivaroxaban
Phase: Launched
Drug: SCH530348
Manufacturer: Schering-Plough
Indication: Acute coronary syndromes
Active ingredient: SCH 530348
Phase: III
Drug: AR-C 126532
Manufacturer: AstraZeneca
Indication: Acute coronary syndromes
Active ingredient: Ticagrelor
Phase: III
Drug: Iscover
Manufacturer: Bristol-Myers Squibb
Indication: Acute coronary syndromes
Active ingredient: Clopidogrel
Phase: Launched
Drug: Crestor
Manufacturer: AstraZeneca
Indication: Acute coronary syndromes
Active ingredient: Rosuvastatin
Phase: III
Source: Wolters Kluwer Health
Recent MM&M Coverage
Effient launch poses puzzle for Lilly, Daiichi Sankyo
Pharmacology
Prasugrel is a platelet activation and aggregation inhibitor whose active metabolite binds the P2Y12 class of ADP receptors on platelets. It should be given with daily aspirin when appropriate, and it may be given with statins, digoxin, drugs that increase gastric pH, GPIIb/IIIa inhibitors, and heparin.
Clinical Trials
In a large, randomized, double-blind, parallel-group study, the use of prasugrel was compared to a regimen of clopidogrel, each added to aspirin and other standard therapy in patients with acute coronary syndrome (UA, NSTEMI, or STEMI) who were to be managed with PCI. Heparin and GPIIb/IIIa inhibitors were administered at the discretion of the treating physician. Oral anticoagulants, other platelet inhibitors, and chronic NSAIDs were not allowed. Patients were followed for at least 6 months.
The primary outcome measure was the composite of cardiovascular death, nonfatal MI, or nonfatal stroke in the UA/NSTEMI population. Prasugrel significantly reduced the total endpoint events compared to clopidogrel (mostly by decreasing nonfatal MIs). The treatment effect was seen within the first few days and persisted until the end of the study.
Prasugrel reduced the occurrence of the primary composite endpoint compared to clopidogrel in both the UA/NSTEMI and STEMI populations.
Except in certain high-risk situations such as diabetes mellitus and prior MI, prasugrel is not recommended for use in patients 75 years of age and older due to an increased risk of bleeding in this age group. Data suggest, however, that prasugrel may reduce the risk of ischemic events in these patients.
Adverse Reactions
Bleeding (may be fatal), hyper- or hypotension, hyperlipidemia, headache, back pain, GI upset, dizziness, cough, chest pain, atrial fibrillation, leukopenia; rare: thrombotic thrombocytopenic purpura, thrombocytopenia, anemia, abnormal hepatic function, allergic reactions, angioedema.
Adults
Loading dose: 60mg once. Maintenance: 10mg once daily. <60kg: consider 5mg once daily. Take with aspirin (75mg–325mg daily).
Children
Not recommended.
Contradictions
Active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage). Prior TIA or stroke. Do not start if patient likely to undergo urgent CABG.
Precautions
≥75yrs: usually not recommended. Weight <60kg, or CABG or other surgery or trauma, or severe hepatic dysfunction: increased risk of bleeding. Discontinue 7 days before surgery, and if TIA or stroke occurs. Premature discontinuation increases risk for cardiac events (eg, stent thrombosis, MI, death). Pregnancy (Cat.B). Nursing mothers.
Interactions
Increased bleeding risk with heparin, warfarin, fibrinolytics, chronic NSAID use.
