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Trade names | Jetrea |
AHFS/Drugs.com | Monograph |
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Routes of administration | Intravitreal |
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Formula | C1214H1890N338O348S14 |
Molar mass | 27237.33 g·mol−1 |
Ocriplasmin (trade name Jetrea) is a recombinant protease with activity against fibronectin and laminin, components of the vitreoretinal interface. It is used for treatment of symptomatic vitreomacular adhesion, for which it received FDA approval on 17 October 2012. It works by dissolving the proteins that link the vitreous to the macula, resulting in posterior detachment of the vitreous from the retina. [1]
Ocriplasmin is an injectable drug that is "a truncated form of the human serine protease plasmin." The protease plasmin still retains its enzymatic properties. [2] Ocriplasmin consists of two polypeptide chains that are linked by disulfide bonds. Additionally, the longer peptide chain has four disulfide bonds. Ocriplasmin is only moderately stable when injected, and this is due to autolytic degradation. [3]
Ocriplasmin can degrade various structural proteins, including laminin and fibronectin, which are localized in the vitreoretinal surface. Here, these two proteins are involved in vitreoretinal attachment. Ocriplasmin is currently being studied in clinical trials and data indicate that it is able to induce posterior vitreous detachment in vitreomacular adhesion patients. [3]
ThromboGenics, the manufacturer of ocriplasmin, encountered several problems when trying to get approval for the drug. In 2012, the FDA brought up the problem of adverse side effects associated with the drug. The FDA stated that the adverse effects may not cause long-term harm, but that conclusion could not be definitively made. [4] Several days later, the FDA endorsed ocriplasmin, which was still an experimental drug. The advisory committee brought up several safety issues, but the committee ended up voting that no additional studies were needed. [5] This may be controversial, considering the drug underwent only two studies. [6]
As part of a deal with Alcon, ThromboGenics received $98.4 million for the ex-US rights to ocriplasmin. This is part of a $500 million-plus deal. ThromboGenics received a $123 million-plus payment, when ocriplasmin gained approved in the Europe Union; this occurred in March 2013. [7] [8]
60% of the market of ocriplasmin is in the United States, with more than a quarter of a million patients. [7]
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collagen, fibrin, and heparan sulfate proteoglycans.
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.
An oligopeptide, often just called peptide, consists of two to twenty amino acids and can include dipeptides, tripeptides, tetrapeptides, and pentapeptides. Some of the major classes of naturally occurring oligopeptides include aeruginosins, cyanopeptolins, microcystins, microviridins, microginins, anabaenopeptins, and cyclamides. Microcystins are best studied, because of their potential toxicity impact in drinking water. A review of some oligopeptides found that the largest class are the cyanopeptolins (40.1%), followed by microcystins (13.4%).
Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide.
Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.
Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally isolated from human urine, and it is also present in the blood and in the extracellular matrix of many tissues. The primary physiological substrate of this enzyme is plasminogen, which is an inactive form (zymogen) of the serine protease plasmin. Activation of plasmin triggers a proteolytic cascade that, depending on the physiological environment, participates in thrombolysis or extracellular matrix degradation. This cascade had been involved in vascular diseases and cancer progression.
Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).
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Cathepsins are proteases found in all animals as well as other organisms. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption. Cathepsins have a vital role in mammalian cellular turnover.
Vertex Pharmaceuticals is an American biopharmaceutical company based in Boston, Massachusetts. It was one of the first biotech firms to use an explicit strategy of rational drug design rather than combinatorial chemistry. It maintains headquarters in South Boston, Massachusetts, and three research facilities, in San Diego, California, and Milton Park, Oxfordshire, England.
Metamorphopsia is a type of distorted vision in which a grid of straight lines appears wavy and parts of the grid may appear blank. People can first notice they suffer with the condition when looking at mini-blinds in their home. For example, straight lines might be wavy or bendy. Things may appear closer or further than they are.
Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment (Fab) created from the same parent mouse antibody as bevacizumab. It is an anti-angiogenic that is approved to treat the "wet" type of age-related macular degeneration, diabetic retinopathy, and macular edema due to branch retinal vein occlusion or central retinal vein occlusion.
Pegaptanib sodium injection is an anti-angiogenic medicine for the treatment of neovascular (wet) age-related macular degeneration (AMD). It was discovered by NeXstar Pharmaceuticals and licensed in 2000 to EyeTech Pharmaceuticals, now OSI Pharmaceuticals, for late stage development and marketing in the United States. Gilead Sciences continues to receive royalties from the drugs licensing. Outside the US pegaptanib is marketed by Pfizer. Approval was granted by the U.S. Food and Drug Administration (FDA) in December 2004.
Désiré, Baron Collen is a Belgian physician, chemist, biotechnology entrepreneur and life science investor. He made several discoveries in thrombosis, haemostasis and vascular biology in many of which serendipity played a significant role. His main achievement has been his role in the development of tissue-type plasminogen activator (t-PA) from a laboratory concept to a life-saving drug for dissolving blood clots causing acute myocardial infarction or acute ischemic stroke. Recombinant t-PA was produced and marketed by Genentech Inc as Activase and by Boehringer Ingelheim GmbH as Actilyse, and is considered biotechnology's first life saving drug.
Aflibercept, sold under the brand names Eylea and Zaltrap, is a medication used to treat wet macular degeneration and metastatic colorectal cancer. It was developed by Regeneron Pharmaceuticals and is approved in the United States and the European Union.
Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. It is a human monoclonal antibody 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.
Vitreomacular adhesion (VMA) is a human medical condition where the vitreous gel of the human eye adheres to the retina in an abnormally strong manner. As the eye ages, it is common for the vitreous to separate from the retina. But if this separation is not complete, i.e. there is still an adhesion, this can create pulling forces on the retina that may result in subsequent loss or distortion of vision. The adhesion in of itself is not dangerous, but the resulting pathological vitreomacular traction (VMT) can cause severe ocular damage.
Eteplirsen is a medication to treat, but not cure, some types of Duchenne muscular dystrophy (DMD), caused by a specific mutation. Eteplirsen only targets specific mutations and can be used to treat about 14% of DMD cases. Eteplirsen is a form of antisense therapy.
Intravitreal injection is the method of administration of drugs into the eye by injection with a fine needle. The medication will be directly applied into the vitreous humor. It is used to treat various eye diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and infections inside the eye such as endophthalmitis. As compared to topical administration, this method is beneficial for a more localized delivery of medications to the targeted site, as the needle can directly pass through the anatomical eye barrier and dynamic barrier. It could also minimize adverse drug effect to other body tissues via the systemic circulation, which could be a possible risk for intravenous injection of medications. Although there are risks of infections or other complications, with suitable precautions throughout the injection process, chances for these complications could be lowered.
Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or retinal detachment. Sickle cell disease is a structural red blood cell disorder leading to consequences in multiple systems. It is characterized by chronic red blood cell destruction, vascular injury, and tissue ischemia causing damage to the brain, eyes, heart, lungs, kidneys, spleen, and musculoskeletal system.