A previous review of the use of LCIG for PD in 2009 by CDR led to the recommendation by CEDAC that LCIG “not be listed” due to the manufacturer’s reported incremental cost per QALY and limitations in the quality of two trials (i.e., their open-label design, small sample sizes, high proportions of withdrawals, administration through an NJ tube, and inclusion of a patient population that was not representative of the target PD population that would be considered for LCIG treatment in Canadian clinical practice).

The CDR systematic review included one DB, double-dummy, phase III, active-controlled RCT (Study 001/002) designed to assess the benefits and harms of LCIG compared with IR OLC and one non-comparative, multinational, multi-centre, open-label, long-term safety study (Study 004) designed to assess the harms of LCIG for the treatment of patients with advanced levodopa-responsive PD who do not have satisfactory control of severe, debilitating motor fluctuations and hyper-/dyskinesia despite optimized treatment with available combinations of PD medicinal products, and for whom the benefits of this treatment may outweigh the risks associated with the insertion and long-term use of the PEG-J tube required for administration.

Compared with IR OLC, LCIG was associated with a statistically significant and clinically meaningful reduction in daily normalized “off” time at week 12 (the primary outcome) completed through the PDHD (Study 001/002). Overall, LCIG was also associated with a statistically significant improvement in daily normalized “on” time without troublesome dyskinesia at week 12 (Study 001/002). The results were primarily driven by the increase in “on” time without dyskinesia, whereas the change in “on” time with non-troublesome dyskinesia was not statistically significant. These results continue to support the benefit associated with LCIG treatment given that the results are being driven by the more desirable component (“on” time without dyskinesia). In general, patients treated with LCIG in Study 004 experienced a significant improvement in daily normalized “off” time and “on” time at week 54 compared with their baselines. The results of other secondary end points adjusted for multiple statistical testing used to assess PD symptoms at week 12 (i.e., the PDQ-39 summary index score and the UPDRS Part II) were also supportive of the primary analysis, demonstrating statistically significant and clinically meaningful improvement in favour of treatment with LCIG (Study 001/002).

Given that the comparator group in Study 001/002 also included levodopa/carbidopa as a treatment, between-treatment AE differences related to LCIG were not expected. Generally, AEs reported in Study 001/002 were known AEs of levodopa/carbidopa (e.g., depression, anxiety, confusion). Furthermore, the safety profile of the patients treated with LCIG in Study 001/002 was also similar to that of patients with advanced PD who have undergone a PEG-J procedure. The long-term safety of LCIG was explored in Study 003 and Study 005 (both open-label safety extension studies of Study 001/002 and/or Study 004 in which patients were treated with open-label LCIG for up to 60 months); the results suggest continued efficacy and no new safety signals compared with baseline.