Continuous subcutaneous levodopa-carbidopa for the treatment of advanced Parkinson’s disease: is it an improvement on other delivery?

ABSTRACTIntroduction Parkinson’s disease (PD) is the second most common neurodegenerative disease and is growing in prevalence and disability. The standard treatment for PD is oral levo-dopa (LD) with carbidopa (CD). As PD progresses, despite higher doses of LD/CD, plasma levels of LD fluctuate, and may be associated with motor fluctuations and dyskinesia.Areas covered The development of two new subcutaneous preparations of LD/CD (ND0612 and ABBV-951) for the treatment of motor fluctuations in PD is described in detail. Both reduce motor fluctuations and dyskinesia with minor infusion site adverse events. A third subcutaneous preparation, DIZ102, is in early-stage development.Expert opinion The premise for using continuous release LD in advanced PD is that steady state levels of LD will prevent motor fluctuations/dyskinesia, but this is not the whole story, and will limit the benefits of subcutaneous continuous release LD. With its present pump system ND0612 cannot be used as monotherapy, whereas ABBV-951 can be. Having to combine with oral LD/CD will complicate the use of ND0612. Both ND0612 and ABBV-951 only cause modest reductions in OFF time. It is not clear whether these subcutaneous preparations will have more benefits than the intestinal gel, which also reduces OFF time and dyskinesia.KEYWORDS: ABBV-951DIZ102intestinal levodopa gellevodopa-carbidopaND0612advanced parkinson’s diseasesubcutaneous Article highlights A major problem in the long-term treatment of Parkinson’s disease, is that as the disease advances, not only does the effectiveness of l-dopa treatment decrease but it also leads to the side effect of dyskinesia.This unpleasant side effect with l-dopa of involuntary erratic writhing movements is distressing for subjects with advanced Parkinson’s disease and has proven difficult to overcome.Subcutaneous continuous delivery of soluble forms of l-dopa in combination with carbidopa are being developed and showing promise in the treatment of advanced Parkinson’s disease.Two subcutaneous preparations, ND0612 and ABBV-951, have been shown to improve OFF time/motor activity or dyskinesis in advanced Parkinson’s disease.One advantage of ABBV-951, over ND061, is that it can be used alone as l-dopa therapy, whereas ND061 must be used with oral l-dopa. Both are relatively safe but can cause infusion site reactions.Although longer efficacy and safety trials are still required, subcutaneous continuous delivery l-dopa preparations are showing promise as a major improvement in the treatment of advanced Parkinson’s disease.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was not funded.