Lisdexamfetamindimesilat (1) – Elvanse®

Attention-deficit/hyperactivity disorder (ADHD) in children aged six years and over as part of an overall therapeutic strategy, where the response to previous treatment with methylphenidate is considered clinically inadequate

• The additional benefit of lisdexamfetamine dimesilate compared with the appropriate comparator therapy, atomoxetine, in children aged six years and over with attention-deficit/hyperactivity disorder (ADHD) as part of an overall treatment strategy, where the response to prior treatment with methylphenidate is considered clinically inadequate, is not proven.
• In summary, the SPD489-317 study could not be used to assess the additional benefit compared with the appropriate comparator therapy; consequently, no proof of additional benefit compared with the appropriate comparator therapy was provided in the pharmaceutical manufacturer’s dossier.
• morbidity
  • The primary endpoint of the study at nine weeks was the time to treatment response, defined as a CGI-I score of 1 or 2.
  • Symptoms (as measured by CGI-S, CGI-I, ADHD-RS-IV and WFIRS-P) were recorded as secondary endpoints.
• The submitted study SPD489-317 is not suitable for establishing any additional benefit of lisdexamfetamine dimesilate over atomoxetine, as there was insufficient documentation to show that the prior treatment formed part of a comprehensive therapeutic plan, nor did the study ensure this.
• It cannot therefore be assumed that the drug is being used in accordance with the marketing authorisation.
• Furthermore, the study duration was too short to allow for a benefit assessment in the context of a chronic condition.
• However, study SPD489-317 does not define any corresponding inclusion criteria for psychological, educational or social interventions that had already been undertaken, and it considers only drug therapy.
• Nor was there any possibility within the scope of the study to initiate such therapeutic strategies.
• No counselling on this matter was provided to the patients or their legal guardians, or at least none was documented.
• The continuation of non-pharmacological adjunctive therapies (i.e. behavioural therapy) was only possible to a limited extent during the study if this therapy had already begun one month prior to randomisation.
• Non-pharmacological interventions were documented in only a minor proportion of study participants (8 %) either concurrently or prior to the study (22 %).
• However, these additional therapeutic measures are a prerequisite for the use of both lisdexamfetamine dimesilate and atomoxetine and should also have been carried out during prior treatment with methylphenidate.
• However, this was not ensured within the framework of the study design and was inadequately documented.
• It cannot therefore be established with the necessary certainty that the medicinal products were used in accordance with the conditions of use set out in the marketing authorisation.
• The necessary adequate documentation of the implementation of the overall therapeutic plan was not ensured.
• The benefit assessment under Section 35a of the German Social Code, Book V (SGB V), however, relates to the benefit assessment of medicinal products within the context of their marketing authorisation.
• Consequently, the study is, on the whole, too short to be able to establish any additional benefit.

Courtesy translation only, please refer to the German original.