Lomitapid (2) – Lojuxta®

• Clinical trials
  • Study 005 is an open-label, single-arm, multicentre study with a treatment duration of 78 weeks.
  • The LOWER study is a multicentre registry study that has been ongoing since 2014 and was planned on a global scale.

a) Patients in whom pharmacological and dietary options for lipid-lowering have been exhausted and who do not receive LDL apheresis

• The additional benefit is not proven.
• The pharmaceutical manufacturer has not provided any data for patients in whom pharmacological and dietary options for lipid-lowering have been exhausted and who are not receiving LDL apheresis treatment.

b) Patients in whom pharmacological and dietary options for lowering lipids have not been exhausted

• Any additional benefit is deemed not proven.
• No data were provided for patients in whom pharmacological and dietary options for lowering lipid levels have not been exhausted.

c) Patients in whom pharmacological and dietary options for lipid-lowering have been exhausted and who are also receiving LDL apheresis treatment

• An additional benefit is not proven.
• For this patient group, the pharmaceutical manufacturer has not identified any direct comparative study of lomitapid against the appropriate comparator therapy.
• Nor was an adjusted indirect comparison based on randomised controlled trials presented in the dossier.
• However, the analyses in the dossier for the benefit assessment, based on the studies mentioned, contain such significant methodological shortcomings that the results are not suitable for determining any potential additional benefit.
• Overall, the information in the statement does not remedy the shortcomings in the benefit assessment data already described.
• Morbidity – LDL-C reduction
  • The dossier presented various analyses for before-and-after comparisons, taking into account the single-arm lomitapide study AEGR-733-005 (hereinafter referred to as Study 005) and its extension study AEGR-733-012 (hereinafter referred to as Study 012), primarily for the endpoint of LDL-C.
  • This reduction in LDL-C could only be demonstrated for week 26 of Study 005; a sustained, longer-term reduction in LDL-C, which is significant in the context of a chronic condition, cannot be inferred from the data.
  • However, the extent to which LDL-C was reduced cannot be quantified due to the inadequate measurement of LDL-C described above.
  • In particular, it is still not possible to determine the LDL burden.
  • The measurements were taken in each case immediately prior to the patients’ LDL apheresis treatment. The result is not suitable for assessing the mean LDL-C concentration, as LDL-C levels drop sharply immediately after LDL apheresis treatment and then rise continuously over the course of several days, possibly until the time of a further apheresis treatment (so-called cholesterol rebound).
  • To obtain an approximate determination of the current LDL-C level, it is therefore necessary to take several readings of the LDL-C value at different times between two apheresis sessions, but at least one further reading must be taken immediately after the apheresis procedure.
• Side effects
  • The dossier presented only AE analyses for the overall population; an analysis of AE events for the potentially relevant patient population of Study 005 and Study LOWER for patient group 1b) was not available.
  • In Study 005, there were 3 serious adverse events (SAEs) and 4 discontinuations due to AEs in the overall population.
  • If all of these had occurred in the potentially relevant patient population of up to 10 patients, this would have affected a significant proportion, namely 30% and 40% of patients respectively.

Courtesy translation only, please refer to the German original.