Aug 1, 2013
Ocriplasmin: indication of major added benefit for certain patients
Improved visual acuity and fewer operations in patients with mild symptoms
The drug ocriplasmin (trade name: Jetrea) has been approved in Germany since March 2013 for the treatment of adults with vitreomacular traction (VMT), in which the vitreous body of the eye is partly stuck to the retina. In an early benefit assessment pursuant to the "Act on the Reform of the Market for Medicinal Products” (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether ocriplasmin offers an added benefit over the current standard therapy.
According to the findings, there is an indication of a major added benefit of ocriplasmin in mild visual impairment, and an indication of considerable added benefit in moderate visual impairment.
Drug aims to resolve adhesion with retina
The vitreous body of the eyeball (corpus vitreum) shrinks with ageing and usually becomes detached from the retina. In VMT, this detachment is incomplete, and the vitreous body is partly stuck to the retina. This can lead to a pulling force on the macula, the area of greatest visual acuity, resulting in distorted or blurred vision, to the point of loss of vision.
The enzyme ocriplasmin is injected into the vitreous body of the eye and aims to dissolve the protein links between the vitreous body and the retina, thus resolving the vision disorder. This might avoid surgery.
The G-BA distinguished between three subpopulations
For patients who only have mild symptoms or none at all, the Federal Joint Committee (G BA) specified watchful waiting, i.e. observation of the disease and further treatment based on the course of the disease, as appropriate comparator therapy. If symptoms are severe, visual acuity continues to get worse and retinal changes occur, treatment with ocriplasmin was to be compared with surgical removal of the vitreous body (vitrectomy).
However, the drug manufacturer's dossier only contained data for mild symptoms, which included mild to moderate visual impairment. The manufacturer excluded adults without symptoms from its research question, and did not present any data for the comparison with the appropriate comparator therapy for adults with severe symptoms. The manufacturer did not claim an added benefit for any of the two subpopulations.
No differences regarding quality of life and side effects
No relevant differences between the treatment with and the treatment without ocriplasmin could be established regarding quality of life. Side effects such as retinal detachment and decreased visual acuity as well as study discontinuations because of side effects were no more common under ocriplasmin than they were under the comparator therapy.
Added benefit with regards to visual acuity and vitrectomy
Visual acuity (independent from the degree of visual impairment) improved in adults with mild symptoms: after treatment with ocriplasmin, more patients could recognize at least two additional lines (ten additional letters) on an eye chart (ETDRS) than the comparator group. This means that they could then recognize all letters from a distance of almost 6.5 metres that, before the treatment, they had recognized from a distance of 4 metres. There is therefore an indication of a considerable added benefit for both degrees of visual impairment.
The studies also showed that people with mild symptoms needed vitrectomy less frequently under ocriplasmin treatment than under the comparator therapy. The added benefit differs regarding the degrees of visual impairment: there is an indication of a major added benefit in mild visual impairment; and a hint of an added benefit, which is non-quantifiable, but not more than considerable, in moderate visual impairment.
Overall, for the subpopulation with mild VMT symptoms, ocriplasmin was found to have the following advantages: there is an indication of a major added benefit of ocriplasmin compared with watchful waiting for people with mild visual impairment; and an indication of a considerable added benefit for people with moderate visual impairment.
Study results are subject to uncertainty
As the results of the studies are uncertain, no proof can be derived from them. For example, placebo injections were given in the control groups of the two bigger ones of the three studies (TG-MV-006 und TG-MV-007). These two studies have a high risk of bias for the comparison with watchful waiting, which is the one of interest, because the injection itself might influence the results.
G-BA decides on the extent of added benefit
The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer’s dossier and IQWiG’s assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G BA then decides on the extent of the added benefit, thus completing the early benefit assessment.
An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the website gesundheitsinformation.de, published by IQWiG, provides easily understandable and brief German-language information on ocriplasmin.
The G-BA website contains both general English-language information on benefit assessment pursuant to §35a Social Code Book (SGB) V and specific German-language information on the assessment of ocriplasmin.
More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on informedhealthonline.org. If you would like to be informed when these documents are available, please send an email to email@example.com.