Latanoprost / Netarsudil (1) – Roclanda®

• Clinical trials
  • The MERCURY 3 study was a randomised, double-blind, parallel-group trial in which the fixed-dose combination of latanoprost and netarsudil was compared on a 1:1 basis with the fixed-dose combination of bimatoprost and timolol.

Adults with primary open-angle glaucoma or ocular hypertension in whom monotherapy with a prostaglandin or netarsudil results in an insufficient reduction in intraocular pressure

• For the treatment of adults with primary open-angle glaucoma or ocular hypertension in whom monotherapy with a prostaglandin or netarsudil results in an insufficient reduction in intraocular pressure, the additional benefit of latanoprost/There is no proof that netarsudil is better than bimatoprost/timolol.
• Overall, there is no additional benefit of latanoprost/netarsudil compared with the appropriate comparator therapy, bimatoprost/Timolol for adults with primary open-angle glaucoma or ocular hypertension, in whom monotherapy with a prostaglandin or netarsudil results in an insufficient reduction in intraocular pressure, does not provide proof that it achieves this outcome.
• mortality
  • In the MERCURY-3 study, no deaths occurred in either study arm within the relevant patient population.
• Morbidity – Visual field impairment
  • In the MERCURY 3 study, the visual field was assessed using automated threshold perimetry.
  • The analyses presented for the endpoint of visual field loss are not used to derive the additional benefit, as no analyses of the binocular visual field are available.
• Morbidity – Best-corrected visual acuity
  • In the study, best-corrected visual acuity was measured using ETDRS-standard eye charts at a distance of 3 to 6 metres.
  • For the endpoint of best-corrected visual acuity, there is no statistically significant difference between the treatment groups.
• Morbidity – Health status (NEI VFQ-25, General Health subscale)
  • The NEI VFQ-25 is a questionnaire designed to measure vision-related quality of life, comprising a total of 26 items and 12 subscales.
  • No statistically significant difference was observed between the treatment groups for the health status endpoint.
• Quality of life – NEI VFQ-25 (total score)
  • The NEI VFQ-25 is a questionnaire designed to measure vision-related quality of life, comprising a total of 26 items and 12 subscales.
  • In the responder analyses, as with the assessments of the mean change at month 6, there was no statistically significant difference between the treatment groups in either case.
• Quality of life – SF-36 (physical and mental health total scores)
  • In the responder analyses, as with the assessments of the mean change at month 6, there was no statistically significant difference between the treatment groups in any case.
• Side effects – discontinuation due to side effects
  • For the endpoint ‘discontinuation due to adverse events’, a statistically significant difference was observed between the treatment groups, to the disadvantage of latanoprost/netarsudil.
  • The supplementary documentation provided by the pharmaceutical manufacturer indicates that only 1 of the 18 events in the latanoprost/netarsudil arm was classified as serious.
• Side effects – ocular side effects
  • For the endpoint ‘ocular adverse events’, there is a statistically significant difference between the treatment groups, with a disadvantage for latanoprost/netarsudil.
  • The documents submitted subsequently by the pharmaceutical manufacturer indicate, however, that the most frequently occurring events are predominantly asymptomatic and often do not affect patients.
• Side effects – SUEs
  • For the SUE endpoint, there was no statistically significant difference between the treatment groups.
• Side effects – ocular SUEs
  • For the endpoint ‘ocular SUEs’, there was no statistically significant difference between the treatment groups.
• Overall assessment
  • The assessment of additional benefit is based on the randomised, double-blind MERCURY 3 study.
  • In addition to the negative effect on the endpoint ‘discontinuation due to AEs’, a detailed analysis also reveals a negative effect on the endpoint ‘ocular AEs’.
  • In the overall assessment of the available results, the negative effects on the endpoints ‘discontinuation due to AEs’ and ‘ocular AEs’ are not sufficient to conclude that latanoprost/netarsudil offers less benefit.
  • Overall, there is an additional benefit of latanoprost/netarsudil compared with the appropriate comparator therapy, bimatoprost/Timolol for adults with primary open-angle glaucoma or ocular hypertension, in whom monotherapy with a prostaglandin or netarsudil does not provide sufficient proof of a reduction in intraocular pressure.
• Due to the high number of deviations from the protocol, the extent to which these influence the results of the MERCURY 3 study remains unclear; the potential for bias across endpoints in the study is therefore assessed as high.
• The reliability of the study results is therefore reduced overall.

Courtesy translation only, please refer to the German original.