Ocriplasmin (2) – Jetrea®

• Clinical trials
  • All five studies were randomised, double-blind, controlled, multicentre trials.
  • Patients with symptomatic focal vitreomacular adhesion, corresponding to VMT, were included.
  • Patients were randomised to two study arms. Patients in the intervention arm received a single intravitreal injection of ocriplasmin, whilst in the control arm, a single injection of placebo (studies TG-MV-006 and TG-MV-007) or a sham injection (studies TG-MV-004, J-12-075, OASIS) was administered.

a) Adults with vitreomacular traction and mild symptoms (e.g. minor deterioration in visual acuity, minor visual disturbances, no progression of symptoms)

• For adult patients with vitreomacular traction and mild symptoms, there is a hint of a minor additional benefit for ocriplasmin compared with a ‘wait-and-see’ approach.
• Overall, based on these considerations, the additional benefit of ocriplasmin compared with the appropriate comparator therapy – watchful waiting – for the treatment of vitreomacular traction (VMT) in adults with mild symptoms is classified as minor.
• Taken as a whole, the uncertainties described justify a classification of the certainty of evidence as ‘a hint of additional benefit’.
• mortality
  • There is no statistically significant difference between the treatment arms, neither in the meta-analysis at month 6 nor in study TG-MV-014 at month 24.
• Morbidity – visual acuity (improvement in visual acuity of ≥ 2 lines)
  • The meta-analysis at month 6 shows a statistically significant advantage of ocriplasmin over a ‘watch-and-wait’ approach [Meta-analysis: RR = 1.57 [95% CI: 1.23; 2.01]; p = 0.007].
  • The analyses of the OASIS study at month 24 do not reveal any statistically significant difference between ocriplasmin and a ‘watch-and-wait’ approach [RR = 1.24 [95% CI: 0.91; 1.71]; p = 0.114].
• Morbidity – Vitrectomy
  • For the patient-relevant endpoint of vitrectomy, the meta-analysis shows a statistically significant advantage for ocriplasmin over a watch-and-wait approach at month 6 [meta-analysis: RR = 0.78 [95% CI: 0.63; 0.95]; p = 0.027].
  • At month 24, the difference between the treatment arms for the endpoint of vitrectomy (OASIS study) is not statistically significant [RR = 0.79 [95% CI: 0.62; 1.00]; p = 0.080].
• Morbidity – metamorphopsia
  • It is currently unclear whether this diagnostic tool can be regarded as sufficiently valid, given the low sensitivity described in the literature.
  • Furthermore, the valid assessment of this endpoint was not ensured in the study (no mandatory assessment was provided for in the study protocol), meaning that no usable data are available for this patient-relevant endpoint for the benefit assessment, neither at month 6 nor at month 24.
• Health-related quality of life – NEI VFQ-25 (change of > 3.6 points, change of ≥ 5 points)
  • The meta-analysis shows a statistically significant advantage in favour of ocriplasmin at month 6 [Meta-analysis: MD = 2.76 [95% CI: 0.75; 4.76]; p=0.019; Hedges’ g: 0.25 [0.06; 0.45]].
  • The responder analyses show a statistically significant advantage in favour of ocriplasmin over a ‘wait-and-see’ approach for the NEI VFQ-25 total score, with a change of > 3.6 points, in the meta-analysis at month 6 [meta-analysis: RR = 1.33 [95% CI: 1.01; 1.75]; p = 0.044].
  • The responder analyses for the pre-specified MID of 5 points in the study protocol also show a statistically significant advantage in favour of ocriplasmin over a ‘wait-and-see’ approach for a change of ≥ 5 points in the NEI VFQ-25 total score, the meta-analysis at month 6 showed a statistically significant advantage in favour of ocriplasmin over a ‘wait-and-see’ approach [meta-analysis: RR = 1.38 [95% CI: 1.10; 1.72]; p = 0.016].
  • The results at month 24 are not usable due to the high proportion of patients excluded from the analysis of the OASIS study (> 30%). As an alternative, the results at month 12 are therefore used for the benefit assessment with regard to quality of life.
  • The responder analyses for the NEI VFQ-25 total score in the OASIS study at month 12 show neither a change of > 3.6 points, nor for a change of ≥ 5 points, a statistically significant advantage or disadvantage for ocriplasmin compared with a ‘wait-and-see’ approach.
• Side effects – SAE
  • For the SUE endpoint, there was no statistically significant difference between the treatment arms, neither in the meta-analysis at month 6 nor in the OASIS study at month 24.
• Overall assessment
  • In summary, at month 6, based on the meta-analysis in the morbidity endpoint category for the endpoints of improvement in visual acuity and vitrectomy, the statistically significant advantages in favour of ocriplasmin over the appropriate comparatorof ‘watch-and-wait’ therapy.
  • At month 24, however, the OASIS study showed no statistically significant differences between ocriplasmin and a ‘wait-and-see’ approach, neither for improvement in visual acuity nor for vitrectomy.
  • In the category of health-related quality of life, taking into account the results of the responder analyses at month 6, there is a statistically significant advantage in favour of ocriplasmin compared with a ‘wait-and-see’ approach; at month 12, no statistically significant advantage for ocriplasmin can be inferred.
  • With regard to the adverse event profile, the meta-analysis at month 6 revealed statistically significant disadvantages for ocriplasmin compared with the appropriate comparator therapy of watchful waiting. These statistically significant differences to the detriment of ocriplasmin persisted at month 24.
  • Overall, at month 6, ocriplasmin showed advantages over a ‘watch-and-wait’ approach in the endpoints ‘vitrectomy’ and ‘improvement in visual acuity’, as well as in health-related quality of life; however, these advantages are not statistically significant after 12 or 24 months. At both month 6 and month 24, there were statistically significant differences in side effects to the detriment of ocriplasmin.

b) Adults with vitreomacular traction and severe symptoms (e.g. progressive deterioration in visual acuity, progressive retinal changes, progressive visual disturbances)

• For adult patients with vitreomacular traction and severe symptoms, the additional benefit of ocriplasmin compared with the appropriate comparator therapy is not proven.
• For the patient population of adults with vitreomacular traction and severe symptoms, the pharmaceutical manufacturer did not submit any study that would have been suitable for assessing the additional benefit of ocriplasmin compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.