See also the contribution of our author Dr. Becker: fluctuations

To deal with these challenges, non-oral follow-up therapies are available:

1. Levodopa pump: A continuous infusion of levodopa and carbidopa via a pump into the small intestine reduces the fluctuations and ensures a more even concentration of the active substance in the blood. As a result, unwanted on-off phases can be reduced and more time can be achieved in good mobility.

2. Apomorphine pump: Apomorphine is a dopamine agonist that is continuously administered subcutaneously via a pump. This continuous supply of active ingredients also helps to reduce fluctuations and prolong the ON phases.

3. Deep brain stimulation (DBS): In DBS, electrodes are implanted in specific areas of the brain to generate electrical impulses. This can reduce movement disorders and reduce the need for additional Parkinson's medications.

The advanced stage of Parkinson's disease can be identified using various criteria such as a constant need for oral L-Dopa, longer OFF phases or impairment by dyskinesia. At this stage, non-oral follow-up therapy should be considered to improve patients' quality of life.

The new pump solutions from AbbVie (ABBV-951) and NeuroDerm (ND0612) offer an innovative way to treat Parkinson's patients with motor fluctuations. Both systems rely on the subcutaneous administration of levodopa and carbidopa for continuous dopaminergic stimulation.

How the new systems work:

1. AbbVie ABBV-951: This system consists of levodopa and carbidopa prodrugs that are continuously delivered into the subcutaneous space via a pump. The prodrugs are converted into the active levodopa in the body. The solubility and concentration of the prodrugs have been optimized to enable delivery of lower dose volumes via a small pump. ABBV-951 aims to close the efficacy gap of orally administered levodopa and extend the therapeutic window.

2. NeuroDerm ND0612: This system also offers continuous subcutaneous infusion of levodopa and carbidopa. It aims to control motor fluctuations and allow for improved ON time without troublesome dyskinesia.

The advantages of subcutaneous administration lie in the continuous dopaminergic stimulation. Compared to oral therapies, fluctuations in drug concentrations in the blood can be minimized, resulting in improved symptom control and prolongation of ON time. Subcutaneous administration allows patients to benefit from a continuous delivery of drug without the surgical intervention associated with other therapy options such as deep brain stimulation.

Promising study results:

AbbVie ABBV-951: In a 12-week phase 3 study involving 130 subjects, ABBV-951 was compared to oral levodopa-carbidopa. Patients receiving ABBV-951 showed a 2,7 hour increase in ON time compared to a XNUMX hour improvement in the oral control group. The improvement was visible after just one week and continued throughout the study.

NeuroDerm ND0612: The system showed positive results in a pivotal study evaluating Parkinson's patients with motor fluctuations. Unfortunately, we do not yet have the exact study results.

However, the exact differences and eventual launch have yet to be confirmed by further research and regulatory decisions.

Jürgen Zender, August 2023