Ocriplasmin (trade name Jetrea) is a recombinant

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

with activity against

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

and

laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...

, components of the vitreoretinal interface. It is used for treatment of symptomatic

vitreomacular adhesion Vitreomacular adhesion (VMA) is a human medical condition where the vitreous gel (or simply vitreous, AKA vitreous humour) of the human eye adheres to the retina in an abnormally strong manner. As the eye ages, it is common for the vitreous to s ...

, for which it received FDA approval on 17 October 2012. It works by dissolving the proteins that link the

vitreous Vitreous may refer to: Materials * Glass, an amorphous solid material ** Vitreous enamel, a material made by fusing powdered glass to a substrate by firing * Vitreous lustre, a glassy luster or sheen on a mineral surface Biology * Vitreous body, ...

to the

macula The macula (/ˈmakjʊlə/) or macula lutea is an oval-shaped pigmented area in the center of the retina of the human eye and in other animals. The macula in humans has a diameter of around and is subdivided into the umbo, foveola, foveal avas ...

, resulting in posterior detachment of the vitreous from the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

Structure

Ocriplasmin is an injectable drug that is "a truncated form of the human serine protease plasmin." The protease plasmin still retains its enzymatic properties. 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.

Mechanism of action

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.

FDA regulation

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. 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. This may be controversial, considering the drug underwent only two studies.

Sales

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 The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been de ...

; this occurred in March 2013. 60% of the market of ocriplasmin is in the United States, with more than a quarter of a million patients.

References

{{reflist Enzymes used as drugs Ophthalmology drugs