Canakinumab (ACZ885), a new biological drug in development, shows potential in treating the most severe form of arthritis in children

·         Human monoclonal antibody canakinumab blocks interleukin 1b, a key chemical messenger that causes inflammation and tissue destruction

·         Majority of children affected by Systemic Juvenile Idiopathic Arthritis (SJIA) with fever and arthritis achieved rapid disease control within 15 days with canakinumab1

·         Symptoms improved by 50% for at least one month in more than half of the patients, while 20% of children achieved complete remission of the disease1

·         Canakinumab already demonstrated long-lasting remission in Cryopyrin-Associated Periodic Syndromes (CAPS), a group of rare autoinflammatory diseases2,3

BASEL, Switzerland, September 15, 2008 – Canakinumab (ACZ885), a fully human monoclonal antibody currently in development to treat a wide range of autoinflammatory diseases, has been shown to rapidly control the disease’s symptoms in children affected by Systemic Juvenile Idiopathic Arthritis (SJIA)1 with fever and arthritis, a kind of juvenile arthritis where interleukin-1b plays a pivotal role in the majority of patients causing inflammation and tissue destruction.

The results were presented today at the 15th Pediatric Rheumatology European Society Congress (PRES) in London and indicate that canakinumab could provide a major therapeutic advance in the treatment of this pediatric inflammatory disorder.

These preliminary data from the Phase I/II study showed more than half of the young patients treated with canakinumab achieved at least 50% control of the disease’s symptoms within 15 days. In addition, four patients achieved complete remission of the disease i.e., no arthritis-inflammation in joints, no fever, and no disease activity according to the physicians’ assessment1.

SJIA is the most severe form of childhood arthritis, characterized by destructive arthritis, fever and rash. Suboptimal treatment can lead to growth retardation, joint and bone disability, as well as serious developmental and social consequences for these young patients4,5. In severe cases, children affected by SJIA can suffer from significant life-threatening complications such as the so-called “Macrophage Activated Syndrome”, mostly due to infections and requiring immediate intensive care6.

“There is an immediate need for improved treatments that give rapid and sustained relief from the debilitating and distressing symptoms experienced by children with SJIA,” said Nicolino Ruperto, MD, MPH, Senior Scientist of the Pediatric Rheumatology International Trial Organization (PRINTO), Istituto Gaslini, Genoa, Italy. “These preliminary data show the significant potential of canakinumab to provide rapid and long-lasting efficacy that can transform the lives of our patients and their families.”

Canakinumab is also being investigated in a Phase III study for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a group of rare but serious life-long diseases including Muckle Wells Syndrome. The Phase II data presented earlier this year demonstrated that CAPS patients treated with canakinumab, after one single dose, achieved complete and long-lasting clinical remission which lasted 115 days on average2,3.

Additional data presented at PRES Congress reinforced the potential of canakinumab to treat CAPS in children. In fact, in young patients aged between four and 17 years, after one single dose, canakinumab was shown to provide long-lasting remission of symptoms of inflammation for an average of close to 90 days7.

Canakinumab is human monoclonal antibody. Unlike other agents, it blocks solely interleukin 1β (IL-1β), one form of the interleukin-1 protein that causes the body to ‘attack’ itself in inflammatory diseases.

The Phase I/II study results presented in London involved 19 children with SJIA aged between four and 19 years, who presented with fever, at least two inflamed joints, and all signs of the systemic inflammation. The study participants received a single subcutaneous injection of canakinumab dosed at 0.5 – 9 mg per kilo, followed by an observation period and re-dosing upon relapse. Eleven of the 19 patients involved in the study responded to canakinumab quickly, an at least 50% improvement of their disease activity versus pre-treatment was observed within two weeks, four patients were even classified as disease-free. Treatment was well-tolerated, the most common adverse events were upper respiratory tract infection1.

SJIA is a form of Juvenile Idiopathic Arthritis (JIA). It is often difficult to manage and many patients suffer poor outcomes6. The disease is characterized by symptoms including daily spiking fever, muscle pain, severe rash and inflammation of major organs such as the heart, and lungs, and hepatosplenomegaly7-10. Unlike other forms of JIA, however, children with SJIA may not develop chronic arthritis until six months or even years after the initial onset of fever6. The term ‘systemic’ refers to the body being affected as a whole. During the course of the disease the systemic sign and symptoms (fever and rash) may disappear leaving the child just with arthritis; this second group of SJIA children has not been considered for inclusion if the Phase I/II study.

SJIA accounts for approximately 10% - 20% of all cases of JIA11 which occur in 30 - 150 per 100,000 children - a similar incidence to juvenile diabetes12. Up to 30% of children with SJIA will still have active disease after 10 years, and the incidence of death in this group is high4.

The potential of canakinumab is reflected in its broad development program. In addition to the Phase II study in SJIA and the Phase III study program in CAPS, canakinumab is also being investigated in more common inflammatory diseases such as rheumatoid arthritis (RA), which affects up to 1% of the world’s population13. A study in RA currently underway uses an innovative tailored approach with biomarkers to predict response to treatment. If successful, this may give suitable patients a personalized approach to treating their disease.

Orphan drug status has already been granted to canakinumab in the European Union and US for the treatment of CAPS, and in the EU for SJIA. Orphan drugs are those designed to treat serious or life-threatening diseases affecting less than 200,000 people (in the US)14 or less than five out of 10,000 people (in the EU)15.

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as “in development”, “potential”, “can”, “being investigated”, “could”, “may”, or similar expressions, or by express or implied discussions regarding potential marketing approvals for canakinumab or regarding potential future revenues from canakinumab. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with canakinumab to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that canakinumab will be approved for sale in any market. Nor can there be any guarantee that canakinumab will achieve any levels of revenue in the future. In particular, management’s expectations regarding canakinumab could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group’s continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 98,000 full-time associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

References

1.        Ruperto, N et al. A phase II trial with canakinumab, a new IL-1β blocking monoclonal antibody (ACZ885), to evaluate preliminary dosing, safety and efficacy profile with systemic Juvenile Idiopathic Arthritis (sJIA), oral presentation at PReS Congress, September 15 2008, London, England.

2.        Lachmann H.J. et al. Treatment of cryopyrin associated periodic fever syndrome with a fully human anti-IL-beta monoclonal antibody (ACZ885): results from a subcutaneous administration study, oral presentation at FMFSAID, April 8 2008, Rome, Italy.

3.        Kuemmerle-Deschner J.B. et al, Long lasting response to ACZ885 in patients with Muckle-Wells Syndrome, oral presentation at FMFSAID, April 8 2008, Rome, Italy.

4.        Ravelli, A. Martini, A. Juvenile idiopathic arthritis. Lancet. 2007 Mar 3;369(9563):767-78.

5.        Woo, P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Prac Rheumatology 2006; 2:1 28-34.

6.        Illowite NT. Current treatment of juvenile rheumatoid arthritis. Pediatrics. 2002; 109-115.

7.        Kuemmerle-Deschner J., et al.ACZ885 (canakinumab), a new IL-1 beta blocking monoclonal antibody provides long-lasting remission in children with Cryopyrin Associated Periodic Syndrome (CAPS), oral presentation at PRES Congress, September 16 2008, London, England

8.        Illowite, NT. Systemic Juvenile Idiopathic Arthritis – A 2006 Update. Medscape. Available at:.www.medscape.com/viewarticle/540239_2. Last accessed on August 22, 2008.

9.        Lomater C, Gerloni V, Gattinara M, et al. Systemic onset juvenile rheumatoid arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J Rheumatol. 2000; 27:491-496.

10.     Wallace CA, Levinson JE. Juvenile rheumatoid arthritis: outcome and treatment for the 1990’s. Rheum Dis Clin North Am. 1991; 17:891-905.

11.     Ansell BM, Wood PN. Prognosis in juvenile chronic polyarthritis. Clin Rheum Dis. 1976; 2:397-412.

12.     Petty RE, Southwood TR, Baum J et al Revision of the Proposed Classification Criteria for Juvenile Idiopathic Arthritis: Durban, 97 Journal of Rheumatology 1998; 25:1991-1994.

13.     Andersson Gare B. Juvenile arthritis –who gets it, where and when? A review of current data on incidence and prevalence. Clin Exp Rheumatology 1999; 17: 367-74.

14.     www.fda.gov/orphan. Last accessed August 22, 2008.

15.     http://ec.europa.eu/health/ph_threats/non_com/rare_6_en.htm. Last accessed August 22, 2008.

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Posted: September 2008

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