Inclacumab

Last updated
Inclacumab
Monoclonal antibody
Type Whole antibody
Source Human
Target selectin P
Clinical data
Other namesLC1004-002
ATC code
  • none
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6452H9930N1730O2024S42
Molar mass 145465.02 g·mol−1

Inclacumab (LC1004-002) (INN) is a human monoclonal antibody designed for the treatment of cardiovascular disease. [1] [2] [3] [4] [5] [6] [7] [8] [9]

The antibody is outlicensed by Roche. [10]

Related Research Articles

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Intravascular ultrasound (IVUS) or intravascular echocardiography is a medical imaging methodology using a specially designed catheter with a miniaturized ultrasound probe attached to the distal end of the catheter. The proximal end of the catheter is attached to computerized ultrasound equipment. It allows the application of ultrasound technology, such as piezoelectric transducer or CMUT, to see from inside blood vessels out through the surrounding blood column, visualizing the endothelium of blood vessels.

<span class="mw-page-title-main">Acute coronary syndrome</span> Medical condition

Acute coronary syndrome (ACS) is a syndrome due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies. The most common symptom is centrally located pressure-like chest pain, often radiating to the left shoulder or angle of the jaw, and associated with nausea and sweating. Many people with acute coronary syndromes present with symptoms other than chest pain, particularly women, older people, and people with diabetes mellitus.

<span class="mw-page-title-main">Percutaneous coronary intervention</span> Medical techniques used to manage coronary occlusion

Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The process involves combining coronary angioplasty with stenting, which is the insertion of a permanent wire-meshed tube that is either drug eluting (DES) or composed of bare metal (BMS). The stent delivery balloon from the angioplasty catheter is inflated with media to force contact between the struts of the stent and the vessel wall, thus widening the blood vessel diameter. After accessing the blood stream through the femoral or radial artery, the procedure uses coronary catheterization to visualise the blood vessels on X-ray imaging. After this, an interventional cardiologist can perform a coronary angioplasty, using a balloon catheter in which a deflated balloon is advanced into the obstructed artery and inflated to relieve the narrowing; certain devices such as stents can be deployed to keep the blood vessel open. Various other procedures can also be performed.

Myocardial stunning or transient post-ischemic myocardial dysfunction is a state of mechanical cardiac dysfunction that can occur in a portion of myocardium without necrosis after a brief interruption in perfusion, despite the timely restoration of normal coronary blood flow. In this situation, even after ischemia has been relieved and myocardial blood flow (MBF) returns to normal, myocardial function is still depressed for a variable period of time, usually days to weeks. This reversible reduction of function of heart contraction after reperfusion is not accounted for by tissue damage or reduced blood flow, but rather, its thought to represent a perfusion-contraction "mismatch". Myocardial stunning was first described in laboratory canine experiments in the 1970s where LV wall abnormalities were observed following coronary artery occlusion and subsequent reperfusion.

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<span class="mw-page-title-main">Left atrial appendage occlusion</span> Medical treatment

Left atrial appendage occlusion (LAAO), also referred to as left atrial appendage closure (LAAC), is a treatment strategy to reduce the risk of blood clots from the left atrial appendage entering the bloodstream and causing a stroke in those with non-valvular atrial fibrillation (AF). The left atrial appendage can be occluded, closed, by an endovascular implant, or by ligation. Occlusion of the left atrial appendage is presently approached with medical devices that can be deployed inside of the heart or externally as a ligature. In non-valvular AF, over 90% of stroke-causing clots that come from the heart are formed in the left atrial appendage.

<span class="mw-page-title-main">Spontaneous coronary artery dissection</span> Uncommon cause of heart attacks mostly affecting younger, healthy women

Spontaneous coronary artery dissection (SCAD) is an uncommon but potentially lethal condition in which one of the coronary arteries that supply the heart, spontaneously develops a blood collection, or hematoma, within the artery wall due to a tear in the wall. SCAD is one of the arterial dissections that can occur.

<span class="mw-page-title-main">Reperfusion therapy</span> Restoring blood flow post-heart attack

Reperfusion therapy is a medical treatment to restore blood flow, either through or around, blocked arteries, typically after a heart attack. Reperfusion therapy includes drugs and surgery. The drugs are thrombolytics and fibrinolytics used in a process called thrombolysis. Surgeries performed may be minimally-invasive endovascular procedures such as a percutaneous coronary intervention (PCI), which involves coronary angioplasty. The angioplasty uses the insertion of a balloon and/or stents to open up the artery. Other surgeries performed are the more invasive bypass surgeries that graft arteries around blockages.

A diagnosis of myocardial infarction is created by integrating the history of the presenting illness and physical examination with electrocardiogram findings and cardiac markers. A coronary angiogram allows visualization of narrowings or obstructions on the heart vessels, and therapeutic measures can follow immediately. At autopsy, a pathologist can diagnose a myocardial infarction based on anatomopathological findings.

<span class="mw-page-title-main">Management of acute coronary syndrome</span>

Management of acute coronary syndrome is targeted against the effects of reduced blood flow to the affected area of the heart muscle, usually because of a blood clot in one of the coronary arteries, the vessels that supply oxygenated blood to the myocardium. This is achieved with urgent hospitalization and medical therapy, including drugs that relieve chest pain and reduce the size of the infarct, and drugs that inhibit clot formation; for a subset of patients invasive measures are also employed. Basic principles of management are the same for all types of acute coronary syndrome. However, some important aspects of treatment depend on the presence or absence of elevation of the ST segment on the electrocardiogram, which classifies cases upon presentation to either ST segment elevation myocardial infarction (STEMI) or non-ST elevation acute coronary syndrome (NST-ACS); the latter includes unstable angina and non-ST elevation myocardial infarction (NSTEMI). Treatment is generally more aggressive for STEMI patients, and reperfusion therapy is more often reserved for them. Long-term therapy is necessary for prevention of recurrent events and complications.

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References

  1. World Health Organization (2011). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 106" (PDF). WHO Drug Information. 25 (4).
  2. Statement On A Nonproprietary Name Adopted By The USAN Council - Inclacumab, American Medical Association .
  3. Stähli BE, Gebhard C, Duchatelle V, Cournoyer D, Petroni T, Tanguay JF, Robb S, Mann J, Guertin MC, Wright RS, L L'Allier P, Tardif JC (November 2016). "Effects of the P-Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention According to Timing of Infusion: Insights From the SELECT-ACS Trial". J Am Heart Assoc. 5 (11). doi:10.1161/JAHA.116.004255. PMC   5210344 . PMID   27852589.
  4. Stähli BE, Tardif JC, Carrier M, Gallo R, Emery RW, Robb S, Cournoyer D, Blondeau L, Johnson D, Mann J, Lespérance J, Guertin MC, L'Allier PL (January 2016). "Effects of P-Selectin Antagonist Inclacumab in Patients Undergoing Coronary Artery Bypass Graft Surgery: SELECT-CABG Trial". J. Am. Coll. Cardiol. 67 (3): 344–6. doi: 10.1016/j.jacc.2015.10.071 . PMID   26796402.
  5. Morrison M, Palermo G, Schmitt C (November 2015). "Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of inclacumab in healthy Japanese and Caucasian subjects". Eur. J. Clin. Pharmacol. 71 (11): 1365–74. doi:10.1007/s00228-015-1938-4. PMID   26363899. S2CID   468125.
  6. Schmitt C, Abt M, Ciorciaro C, Kling D, Jamois C, Schick E, Solier C, Benghozi R, Gaudreault J (June 2015). "First-in-Man Study With Inclacumab, a Human Monoclonal Antibody Against P-selectin". J. Cardiovasc. Pharmacol. 65 (6): 611–9. doi:10.1097/FJC.0000000000000233. PMC   4461388 . PMID   25714598.
  7. Schmitt C, Mudie N, Ciorciaro C, Gaudreault J (April 2015). "Absence of pharmacodynamic interaction between inclacumab and heparin in healthy smokers". J. Cardiovasc. Pharmacol. 65 (4): 386–92. doi:10.1097/FJC.0000000000000211. PMID   25602360. S2CID   19526048.
  8. Tardif JC, Tanguay JF, Wright SR, Duchatelle V, Petroni T, Grégoire JC, Ibrahim R, Heinonen TM, Robb S, Bertrand OF, Cournoyer D, Johnson D, Mann J, Guertin MC, L'Allier PL (May 2013). "Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-ST-segment elevation myocardial infarction: results of the SELECT-ACS trial". J. Am. Coll. Cardiol. 61 (20): 2048–55. doi: 10.1016/j.jacc.2013.03.003 . PMID   23500230.
  9. Kling D, Stucki C, Kronenberg S, Tuerck D, Rhéaume E, Tardif JC, Gaudreault J, Schmitt C (May 2013). "Pharmacological control of platelet-leukocyte interactions by the human anti-P-selectin antibody inclacumab--preclinical and clinical studies". Thromb. Res. 131 (5): 401–10. doi:10.1016/j.thromres.2013.02.020. PMID   23522853.
  10. "Form 8K - Entry into a Material Definitive Agreement Between Global Blood Therapeutics, Inc. and Hoffmann-La Roche Inc". United States Securities and Exchange Commission.