Stories - More Than Skin Deep

An antibody drug could change the way we treat psoriasis

The discovery and advancement of the antibody drug AIN457 for the treatment of psoriasis underscores key features of NIBR research strategy: its focus on molecular pathways, a growing emphasis on biologic therapies and intense collaborations between scientists and clinicians.

AIN457 is a therapeutic antibody that represents an exciting new kind of medicine for psoriasis  – an autoimmune disease that affects approximately 3% of the world population. The disease is characterized by chronic inflammation resulting in raised, red scaly patches on the skin. In addition, 40% of psoriasis patients develop psoriatic arthritis, a disabling joint disease. The search for safe and effective psoriasis treatments is a challenge that has confounded many research efforts across the globe. Here at NIBR, a unique approach offers hope.

 

Pathways to drug discovery

Drug discovery at NIBR focuses on molecular pathways, a series of molecules that transmit vital information within and between cells. These pathways represent a fundamental mechanism that controls many basic functions of life. NIBR scientists develop small molecule drugs or antibodies to target key nodes within pathways that, when defective, lead to disease.

 

Collaborating to understand disease mechanisms

In 2005, one such node was discovered when NIBR scientists collaborated with academic researchers in the Netherlands. This collaboration identified the role of Interleukin-17 (IL-17) in psoriasis. Under normal circumstances, specialized immune cells called “Th-17” cells secrete IL-17 to help protect against attack by certain microorganisms and fungi. When falsely triggered, the IL-17 molecules can cause inflammation in surrounding tissue. That inflammation can lead to conditions such as psoriasis, arthritis, multiple sclerosis and other rare but serious conditions. NIBR researchers theorized that blocking IL-17 might be able to bring a host of autoimmune conditions under control.

 

Biotechnology that makes a difference in patients’ lives

AIN457 is an antibody targeted to bind IL-17. As an antibody, it is uniquely configured to bind to large molecules, such as IL-17, in the bloodstream and the space between cells preventing them from triggering inflammation. It is also highly specific, and will bind to IL-17 and little else.

In 2007, physician-scientists in the Translational Medicine Group helped design a Proof-of-Concept (PoC) clinical trial for AIN457. This study provided an early read on the safety and effectiveness of the drug in a small, well-defined group of patients. The results exceeded expectations when a single infusion of the antibody was able to provide relief from psoriasis symptoms for more than three months in a majority of patients.
Biologic therapies such as the AIN457 antibody are becoming increasingly important to the Novartis pipeline. Monoclonal antibodies and other protein-based drug candidates already comprise over 25% of the Novartis pre-clinical portfolio.

 

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