Central Nervous System (CNS) Therapy Area includes medicines for the treatment of neurological and psychiatric diseases. Also pain medicines with a central mode of action (especially medicines for the treatment of neuropathic pain) belong to the CNS Therapy Area.

There are several experienced drug development professionals and experts with academic merits developing new medicines for CNS indications at Orion. During the recent years, Orion’s own CNS research has focused on Parkinson’s disease (PD) thanks to successful development programs and registrations.

Development of selegiline, a MAO-B enzyme inhibitor, was mainly done in the late 1970’s and early 1980’s in collaboration between Farmos and Chinoin Pharmaceuticals. Selegiline (Eldepryl®) was successfully launched first in the UK in 1982 and thereafter in several other countries. Selegiline was also investigated in Alzheimer’s disease, but significant efficacy was not seen. 

Stalevo

Orion has developed entacapone, a COMT enzyme inhibitor, on its own from the very beginning until registration. Entacapone is used with levodopa to treat PD patients with wearing-off symptoms. Entacapone decreases the breakdown of levodopa in peripheral circulation so that more levodopa is delivered to the brain.

Entacapone was first launched as a stand-alone tablet (Comtess®/Comtan®) in 1998 and later in 2003 in a  combination tablet together with levodopa (Stalevo®, levodopa/carbidopa/entacapone). Many successful Phase IV studies have been conducted after Stalevo entered the markets. Life cycle management has also included the development of new strengths of Stalevo. Stalevo was first available in three strengths (Stalevo 50, 100 and 150 mg) and during the past two years, new Stalevo 75, 125, 175 and 200 mg strengths have been approved in the US and Europe. Orion now provides seven different strengths for patients using Stalevo. This is more than with any other levodopa product on the market.  Two Phase IIIb clinical studies have been conducted with Stalevo for extending the product's indication to patients with early PD. The findings from these studies indicate, however, that Stalevo does not provide a consistent rist/benefit profile for the early Parkinson's disease patient population at the dosing regimen tested.

Entacapone products have captured a significant market share in the treatment of PD. Entacapone sales (Comtess®/Comtan® and Stalevo®) are by far the biggest in value among all Orion’s products at present. Entacapone has already over 2,7 million patient years. Stalevo is marketed in over 80 countries. After the first launch of entacapone, Novartis has been an important partner for Orion in marketing, selling and further developing the entacapone franchise.

There are some late phase clinical studies on-going with Stalevo.

Orion is developing a new more effective levodopa product based on optimised new formulations and doses of known compounds. Product development is in the clinical trials phase.

New drug candidates

Within CNS therapy area, a specific alfa2C-receptor blocker developed by Orion is another drug molecule currently in the clinical Phase. None of the currently marketed drugs have a similar profile of mode of action. Orion has completed the phase 1 clinical trials and begun phase 2 trials with the alpha 2c receptor antagonist. Early-phase research found that the partially developed drug was potentially suited to the treatment of Alzheimer's disease and Raynaud's phenomenon.

In non-clinical CNS research, Orion has several on-going projects investigating molecules with different mode of actions. It is anticipated that these projects will generate promising drug candidates for clinical development. Orion continues projects aiming for further improvements in levodopa therapy, but research has been actively directed also towards other CNS indications than PD.

Experts in CNS research and development have an important role in evaluating in-licensing candidates for CNS indications. In-licensing evaluations are carried out together with Business Development and Proprietary Product Business. In-licensing activities are looking for partnerships for developing new drug candidates. This will support and strengthen Orion’s own proprietary molecule portfolio. In-licensing evaluations have included molecules that are both in non-clinical research Phase and, also in late clinical development.