Solriamfetol (1) – Sunosi®

• Clinical trials
  • In its dossier for the assessment of the additional benefit of solriamfetol, the pharmaceutical manufacturer does not present any direct comparative studies against the appropriate comparator therapy.
  • However, the RCTs submitted involving solriamfetol and modafinil, as well as the indirect comparisons based on these studies, are not suitable for the present benefit assessment.

a) Adult patients with narcolepsy without cataplexy

• The G-BA has designated modafinil or pitolisant as the appropriate comparator therapy.
• Overall, for adult patients with narcolepsy without cataplexy, the additional benefit of solriamfetol compared with the appropriate comparator therapy is not proven.
• The pharmaceutical manufacturer has not provided any relevant data in the dossier for the assessment of the additional benefit of solriamfetol compared with the appropriate comparator therapy for adult patients with narcolepsy without cataplexy.
• The G-BA considers that, taken as a whole, the indirect comparisons presented are not suitable for deriving patient-relevant effects regarding the additional benefit of solriamfetol.
• Due to methodological limitations, the indirect comparisons submitted are not suitable for addressing the issue of benefit assessment.
• Indirect comparison: Solriamfetol vs. Modafinil
  • In the absence of direct comparative studies, the pharmaceutical manufacturer has submitted an indirect comparison (patient group a: solriamfetol versus modafinil via the bridge comparator placebo) based on RCTs involving solriamfetol and modafinil.
  • For instance, the restrictions on pre-treatment and concomitant medication permitted in the RCTs for the treatment of excessive daytime sleepiness and/or cataplexy differed in some respects.
  • Furthermore, there was no individualised dose adjustment of solriamfetol and modafinil based on the patient’s response, as recommended in the respective summary of product characteristics (SmPC).
  • Furthermore, the RCTs considered by the pharmaceutical manufacturer for the indirect comparisons had a study duration of 8 weeks in the comparison arm and are therefore too short to draw conclusions regarding additional benefit in the present therapeutic indication.
  • Irrespective of the aspects mentioned above, the studies cited by the pharmaceutical manufacturer for patient group a are also not sufficiently similar for an indirect comparison (including differences in prior and concomitant treatment of the patients included in the studies).
• Indirect comparison of solriamfetol versus pitolisant
  • As already described under patient group a, in the dossier the pharmaceutical manufacturer has also addressed a further, common research question against the alternative appropriate comparator therapy, pitolisant.
  • The indirect comparison submitted for this purpose—between the solriamfetol study 14-002 and the pitolisant studies HARMONY I and HARMONY Ibis, using placebo as the bridging comparator — is, similarly to the rationale for the indirect comparison of solriamfetol versus Modafinil (study duration too short; no individualised dose adjustment of Solriamfetol or Pitolisant in accordance with the recommendations in the respective SmPC; formal lack of separation into patient groups a and b as specified by the appropriate comparator therapy).
  • Furthermore, the studies cited by the pharmaceutical manufacturer are not sufficiently similar in terms of the patient group under investigation to allow for an indirect comparison.

b) Adult patients with narcolepsy and cataplexy

• The G-BA designated sodium oxybate or pitolisant as the appropriate comparator therapy.
• Overall, for adult patients with narcolepsy and cataplexy, the additional benefit of solriamfetol compared with the appropriate comparator therapy is not proven.
• The pharmaceutical manufacturer has not submitted any relevant data in the dossier for the assessment of the additional benefit of solriamfetol compared with the appropriate comparator therapy for adult patients with narcolepsy and cataplexy.
• The G-BA considers that, taken as a whole, the indirect comparisons presented are not suitable for deriving patient-relevant effects regarding the additional benefit of solriamfetol.
• Due to methodological limitations, the indirect comparisons submitted are not suitable for addressing the issue of benefit assessment.
• Indirect comparison: Solriamfetol vs. sodium oxybate
  • In the absence of direct comparative studies, the pharmaceutical manufacturer presents, by analogy with patient group a, an indirect comparison (patient group b: solriamfetol versus sodium oxybate via the bridge comparator placebo) based on RCTs involving solriamfetol and sodium oxybate.
  • For instance, the restrictions on pre- and concomitant medication permitted in the RCTs for the treatment of excessive daytime sleepiness and/or cataplexy differed in some respects.
  • Furthermore, there was no patient-specific dose adjustment of solriamfetol and sodium oxybate based on response, as recommended in the respective summary of product characteristics (SmPC).
  • Furthermore, the RCTs considered by the pharmaceutical manufacturer for the indirect comparisons had a study duration of 8 weeks in the comparison arm and are consequently too short to draw conclusions regarding additional benefit in the present therapeutic indication.
  • Irrespective of the aspects mentioned above, the studies cited by the pharmaceutical manufacturer for patient group b are also not sufficiently similar for an indirect comparison (including differences in prior and concomitant treatment of the patients included in the studies).
• Indirect comparison of solriamfetol versus pitolisant
  • As already described under patient group a, in the dossier the pharmaceutical manufacturer has also addressed a further, common research question against the alternative appropriate comparator therapy, pitolisant.
  • As already justified for patient group a, this submitted indirect comparison of the solriamfetol study 14-002 and the pitolisant studies HARMONY I and HARMONY Ibis, using placebo as the bridge comparator, is also not suitable for benefit assessment (study duration too short; no patient-specific dose adjustment of solriamfetol or pitolisant in accordance with the recommendations in the respective SmPC; formally, no separation into patient groups a and b as specified by the appropriate comparator therapy).
  • Furthermore, the studies cited by the pharmaceutical manufacturer are not sufficiently similar in terms of the patient group under investigation to allow for an indirect comparison.

Courtesy translation only, please refer to the German original.