Ocriplasmin
| Ocriplasmin | ||
|---|---|---|
| Mass / length primary structure | 27.5 kilodaltons | |
| Identifier | ||
| External IDs |
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| Drug information | ||
| ATC code | S01 XA22 | |
| DrugBank | DB08888 | |
| Enzyme classification | ||
| Substrate | Laminin, fibronectin, collagen | |
Ocriplasmin is a drug from the group of proteases , which is used in ophthalmology for the treatment of vitreomacular traction (VMT) in adults, also in connection with a macular hole ≤ 400 µm. Ocriplasmin is a shortened form of human plasmin, which is produced by means of recombinant DNA technology in a Pichia pastoris expression system. The drug is manufactured under the trade name Jetrea by the Belgian biopharmaceutical company ThromboGenics NV, which markets the drug in the United States. Alcon , a division of Novartis , acquired the rights to commercialize ocriplasmin outside the United States.
Application areas / indications
In the EU, ocriplasmin has been approved since March 2013 as the first and so far only drug for the treatment of vitreomacular traction (VMT) in adults, also in connection with a macular hole ≤ 400 µm in diameter. Ocriplasmin is currently available in Germany, Great Britain, Sweden, Denmark, Finland, Norway and the Netherlands (as of October 2013). Ocriplasmin was approved in the United States in October 2012 for the treatment of patients with symptomatic vitreomacular adhesion (VMA) and in Canada in August 2013.
type of application
Ocriplasmin is given as a single intravitreal injection into the vitreous humor of the affected eye. The recommended dose is 0.125 mg, which corresponds to 0.1 ml of the diluted solution.
Working principle
If, during the natural, aging-related liquefaction of the vitreous body, protein connections remain between the vitreous body and the rear retina in the area of the yellow spot ( macula ), tensile forces can occur on the macula. If these are perceived by those affected as visual impairment in the form of metamorphopsia , distorted vision or visual field defects - as a result of macular holes - then the indication of vitreomacular traction (VMT) is present.
Ocriplasmin is an enzyme with serine protease activity that has a proteolytic effect on protein components of the vitreous humor and the internal limiting membrane (membrana limitans interna = ILM), e.g. B. Laminin , Fibronectin and Collagen . The intravitreal administration of ocriplasmin aims to break down laminin, fibronectin and collagen, on the one hand to break down the protein connections between the vitreous humor and the ILM and, on the other hand, to further liquefy the vitreous humor. This process of enzymatic vitreolysis is supposed to release traction and enable the closure of macular holes that have already formed.
Clinical data
The efficacy and safety of ocriplasmin have been investigated in two international, multicenter, randomized , double-blind , placebo- controlled studies in patients with VMT. A total of 652 patients (464 ocriplasmin and 188 placebo) were randomized into these two pivotal studies (TG-MV-006 and TG-MV-007) . Patients in the ocriplasmin group received an intravitreal ocriplasmin injection (125 µg in 0.10 ml solution), while those assigned to the placebo group received an intravitreal 0.10 ml injection of the same vehicle. Patients were assessed at baseline, on the day of injection, and on days 7, 14, 28, 90 and 180 after treatment. The primary endpoint was the VMT solution on day 28.
Study data published in the New England Journal of Medicine shows that 26.5% of ocriplasmin-treated patients had their VMT resolved by day 28 (versus 10.1% for placebo [p <0.001]). In addition, 40.6% of ocriplasmin patients achieved macular hole closure on day 28 (compared to 10.6% for placebo [p <0.001]). Patients with a macular hole of ≤ 250 µm responded even better to the treatment: in 58.3% of the patients treated with ocriplasmin the macular hole had closed again; in the placebo group it was 16%. The macular hole had also closed again in 36.8% of the patients with macular holes between 250 and 400 µm, whereas it was only 5.3% of the patients in the placebo group.
All adverse drug reactions (ADRs) of ocriplasmin treatment were ocular in nature. The most common side effects reported were " flying mosquitos ", vitreous opacity, blurred vision, eye pain, and photopsia , as well as conjunctival bleeding caused by the injection procedure. Most of the side effects occurred within the first week after the injection, were not serious, and resolved within 2 to 3 weeks. The incidence of serious adverse reactions across all clinical trials was 2.2% in ocriplasmin-treated patients versus 2.4% in control patients.
There are no data on the use of ocriplasmin during pregnancy and breastfeeding.
Pharmacokinetics
The ocriplasmin levels in the vitreous humor drop rapidly after intravitreal administration: In a clinical study, 2 to 4 hours after administration of 0.125 mg of active ingredient, the ocriplasmin activity was 9% of the theoretical starting concentration. After 7 days they were below the detection limit. Due to the low dosage of ocriplasmin and its rapid deactivation, no detectable drug levels in the systemic circulation are to be expected.
Drug interactions
No compatibility studies have been carried out to date . Accordingly, no clinical data are available on the concomitant use of ocriplasmin and VEGF inhibitors.
Early benefit assessment according to § 35a SGB V
Evaluation of the Institute for Quality and Efficiency in Health Care (IQWIG)
In its report from August 2013, the Institute for Quality and Efficiency in Health Care (IQWiG) recognized ocriplasmin as an indication of an additional benefit in VMT patients with mild symptoms: IQWiG saw an indication for patients with slight visual impairment (> 60 letters EDTRS) for a considerable additional benefit of the drug compared to the appropriate comparator therapy “ observing waiting ”. In the case of moderate visual impairment (35–60 letters EDTRS), the institute found an indication of considerable added benefit.
Decision of the Federal Joint Committee (G-BA)
The Federal Joint Committee (G-BA) has recognized ocriplasmin as having a considerable additional benefit in VMT patients with mild symptoms.
literature
- Peter Stalmans et al .: Enzymatic Vitreolysis with Ocriplasmin for Vitreomacular Traction and Macular Holes. In: New England Journal of Medicine. 367, 2012, pp. 606-615, doi: 10.1056 / NEJMoa1110823 .
- Vera K. Schmit-Eilenberger, Albert J. Augustin: Ocriplasmin opens up new avenues in the therapy of vitreomacular traction. In: Expert Review of Ophthalmology. 8, 2013, pp. 407-411, doi: 10.1586 / 17469899.2013.840536 .
- Jay S. Duker et al .: The International Vitreomacular Traction Study Group Classification of Vitreomacular Adhesion, Traction, and Macular Hole. In: Ophthalmology. 120, 2013, pp. 2611–2619, doi: 10.1016 / j.ophtha.2013.07.042 .
Individual evidence
- ↑ a b Peter Stalmans et al .: Enzymatic Vitreolysis with Ocriplasmin for Vitreomacular Traction and Macular Holes. In: New England Journal of Medicine . 367, 2012, pp. 606-615, doi: 10.1056 / NEJMoa1110823 .
- ↑ Data on file. ThromboGenics, Inc. 2013 (in Alcon Pharma press release of August 2, 2013): IQWiG sees an indication of added benefit with the eye drug Jetrea® (ocriplasmin).
- ↑ a b c Public Assessment Report (EPAR) of the European Medicines Agency (EMA) on: Ocriplasmin .
- ↑ R. Told, M. Baratsits, G. Garhöfer, L. Schmetterer: ETDRS (Early Treatment Diabetic Retinopathy Study) -Visus . In: The ophthalmologist . tape 110 , no. 10 , October 2013, p. 960-965 , doi : 10.1007 / s00347-013-2813-2 .
- ↑ Ocriplasmin: indication of major added benefit for certain patients . IQWiG press release of August 1, 2013.
- ↑ G-BA Medicinal Products Directive / Annex XII: Ocriplasmin . Decision of October 17, 2013, entered into force on October 17, 2013.
