Proof in pathways: Ilaris brings new hope to patients



With a focus on patient need and the molecular cause of several related diseases, Novartis scientists discovered and rapidly developed Ilaris® – a new biological therapy recently approved for a rare but serious group of auto-inflammatory disorders.

In June 2009, Novartis R&D celebrated a key milestone in its pathways approach to drug discovery. The US Food and Drug Administration (FDA) approved Ilaris (canakinumab) for the treatment of children and adults with Cryopyrin-Associ¬ated Periodic Syndrome (CAPS), a collection of rare but life-long auto-inflammatory disorders with debilitating symptoms.

CAPS includes diseases such as Familial Cold Auto-Inflammatory Syndrome (FCAS), Neonatal-Onset Multisystem Inflammatory Disease (NOMID), and Muckle-Wells Syndrome (MWS), disorders resulting in daily fevers, rash, conjunctivitis, painful swollen joints and hearing loss. MWS and NOMID can also lead to potentially fatal complications.

 

A scientific understanding of disease

 Novartis entered CAPS as a disease area by first investigating Muckle-Wells Syndrome. Few people have heard of MWS because not many patients – only around 6,500 people worldwide – suffer from the disease. MWS was known to physician-scientists at the Novartis Institutes for BioMedical Research (NIBR) who recognized the molecular pathway that contributed to the disease.

“Our goal is to develop novel therapies based on our knowledge of disease mechanisms,” said Tim Wright, Head of Translational Sciences at NIBR. “We knew that a single gene mutation leads to the overproduction of interleukin-1-beta (IL-1ß), a protein that causes sustained inflammation and tissue damage. In 2005, we confirmed in a well-defined Proof-of-Concept trial that blocking the IL-1ß protein was an extremely effective treatment for Muckle-Wells Syndrome.”

 

Meeting patient need

 Ilaris was developed to specifically block the IL-1ß protein to limit damage to tissues where it was produced. After the pivotal PoC trial, the FDA granted fast track status of the antibody based on its potential to meet an important unmet medical need for patients with CAPS. In subsequent clinical trials, Ilaris produced rapid and sustained remission of symptoms in up to 97 percent of CAPS patients, with most responding from the first injection. With evidence that the medicine could help CAPS patients, the FDA granted priority review.

“We got the approval in a very short time with a priority review in the US. This shows how important Ilaris is for these patients,” said Thomas Jung, Global Head of Development Franchise Immunology & Infectious Diseases (IID). “We can be very proud of our common efforts between research, the biologics unit, and development in getting this medicine to patients as soon as possible.”

 

Improving quality of life

“It is a very satisfying feeling to get an approval in an indication where patients have been miserable without the right treatment,” says Hermann Gram, Senior Research Investigator in the Autoimmune, Transplantation and Inflammation (ATI) Disease Area, who has been involved with the project from discovery through the clinic. “For some patients, Ilaris has made a huge difference. When I hear people say ‘your medicine has changed my life or my kid’s life’ – it’s really something. This is very gratifying for me as a scientist.”

Until now, CAPS patients, particularly children, had very limited treatment options and relied on medicines that suppressed the entire immune system or required more frequent injections.

“Ilaris gives patients who will benefit from an anti-IL-1ß-based therapy more choices,” said Dhavalkumar Patel, Global Head of the ATI Disease Area at NIBR. “It gives them a medicine that they won’t have to inject every day or every week. A subcutaneous administration just every two months is a fantastic improvement in the lives of patients.”

 

Proof in pathways: testing treatment in related diseases

 In addition to ongoing studies in CAPS, clinical trials with Ilaris are also under way in other diseases involving the IL-1ß pathway. Parallel studies include Systemic Juvenile Idiopathic Arthritis (SJIA), and more common disorders such as gouty arthritis or Chronic Obstructive Pulmonary Disease (COPD).

“Our focus now is to establish whether this could also provide a new approach to the treatment of other diseases involving a similar underlying process.”
Trevor Mundel, Head of Global Development

“By concentrating initially on a rare syndrome with a well-defined disease process such as CAPS, we have been able to demonstrate a clear therapeutic advantage with Ilaris,” said Trevor Mundel, Head of Global Development. “Our focus now is to establish whether this could also provide a new approach to the treatment of other diseases involving a similar underlying process.”

 

 

Back to top