Breakthrough

L-DOPA Therapy for the Treatment of Advanced Parkinson’s Disease
Berlirem GmbH has re-invented the therapy for PD patients suffering from severe motor fluctuations and hyperkinesia (excessive movement) or dyskinesia (involuntary movement). Also, the new method offers a solution for cases when available combinations of Parkinson’s medicinal products have not given satisfactory results.
Chronic oral L-DOPA therapy using levodopa (LD) and carbidopa (CD) is often associated with the development of motor complications, that correlate to fluctuating levodopa plasma concentrations. Continuous dopaminergic stimulation (CDS) is considered to be the optimal method for treating affected PD patients. While various oral treatment regimen failed to fill the gap, the current intra-jejunal infusion system (LCIG, DUODOPA®) requires invasive surgery with all possible negative implications. Subcutaneous infusion (sc) of levodopa is the solution to reach the CDS aim providing a better tolerated and more convenient route of continuous levodopa delivery.

Two companies currently compete for the optimal technology. Tanabe (ND-0612) develops a mixture of LD and CD at a mass ratio of 8:1 while AbbVie (ABBV-951, PRODUODOPA®) has marketed a mixture of Foslevodopa (FLD) and Foscarbidopa (FCD) at a mass ratio of 20:1). Since high L-DOPA doses are to be given (to reach high constant plasma levels), the ND-0612 approach faces a rather low local skin tolerance, and both approaches face limited LD-steady-state levels of clearly below 1000 ng/ml. Higher levels are needed to successfully treat patients with severe PD.

Since 1975, LD has been a cornerstone in the treatment of Parkinson’s disease, administered alongside with CD or benserazide (BZ) to inhibit peripheral LD decarboxylation. In all existing oral formulations of LD/CD(BZ), the total daily dose of CD(BZ) is conventionally capped at 200 mg/day.
However, recent research by Berlirem challenges this practice. As shown for sc-infused LD, much higher and equally distributed CD doses (ranging from 600 to 1200 mg/day) are imperative for an almost complete inhibition of peripheral LD decarboxylation. This change of paradigm, not to increase the LD dose more and more but to increase the peripheral LD stability and thereby reaching higher LD plasma and effect levels, is the breakthrough patented by Berlirem.
In the ongoing development projects, the method developed for BRM 203 will be combined with ND-0612 and PRODUODOPA. Equally distributed, high oral CD doses are expected to triple the LD plasma levels known for these products. Consequently, significantly lower sc LD doses and highly improved skin tolerability will result as well as completely abolishment of peripheral dopaminergic side effects.

Berlirem GmbH

Berlirem is a pharmaceutical company developing new concepts for continuous parenteral application of Levodopa and related compounds for therapy of Parkinson’s Disease.

Levodopa is highly effective in treating the symptoms of Parkinson’s Disease and has been the gold standard of Parkinson’s Disease therapy for more than 50 years. Yet, conventional oral Levodopa therapy does not exploit the full therapeutic potential of this drug. There remains an unmet need for more stable and continuous drug delivery.
To solve this important challenge of Parkinson’s Disease therapy Berlirem is developing prodrugs of levodopa as well as new treatment schedules for levodopa/carbidopa combinations effective in predictable and stable levodopa plasma levels meeting the requirements of a continuous dopaminergic stimulation (CDS).

Contact us

Phone: +49(0)30 288 69 878
Fax: +49(0)30 288 69 696
eMail: info@berlirem.com

Berlirem GmbH

Breite 1
15806 Zossen
Germany

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