Basel, Switzerland (ots/PRNewswire) -
- Not for US Media
- New Ilaris Data in The New England Journal of Medicine Show
Rapid Sustained Efficacy in Patients With Cryopyrin-Associated
Periodic Syndrome (CAPS)(1)
- CAPS is a Debilitating Genetic Disorder With Potentially Fatal
Complications and Limited Treatments Available(1),(2),(3)
- Ilaris Selectively Blocks Interleukin-1beta (IL-1beta), a Key
Driver in Inflammation and Tissue Destruction - Therapy Being
Investigated for Other Inflammatory Diseases(1),(3),(4)
- Regulatory Submissions Completed in Major Countries With
Priority Review Granted in US, Switzerland and Australia
New results from a one-year Phase III study have confirmed that
the investigational biological therapy Ilaris(R) (canakinumab,
formerly ACZ885)[*] produced rapid and sustained remission of
symptoms in the majority of children and adults with a rare and
potentially life-threatening auto-inflammatory disease called
cryopyrin-associated periodic syndrome (CAPS)(1),(2),(3).
The study showed that more than 90% of CAPS patients treated with
Ilaris (28 out of 31) remained in remission at the end of the final
four-month phase of the study(1). This finding supported interim data
from earlier phases showing efficacy in 97-100% of patients(1),(5).
The full results have now been published in The New England Journal
"This study represents an important step forward for the rare
disease community, as canakinumab treats the underlying causes of
CAPS rather than just the symptoms," said Helen J. Lachmann, MD of
the UK National Amyloidosis Centre at the Royal Free and University
College Medical School in London, UK. "In the study, patients
experienced a benefit within hours after receiving a single dose of
canakinumab and only needed further treatment every two months to
control their symptoms. This may give canakinumab a significant
advantage over current therapies in an area of unmet medical need."
CAPS includes a number of lifelong diseases associated with a
gene mutation and characterized by the overproduction of interleukin
1-beta (IL-1beta), a protein (or cytokine) that has a pivotal role in
driving inflammation and tissue destruction(1),(2),(6),(7). The
clinical benefits of Ilaris, a fully human monoclonal antibody, are
due to its selective and long-lasting blockade of IL-1beta(1),(6). By
neutralizing IL-1beta for a sustained period, Ilaris switches off all
symptoms of inflammation in CAPS, as demonstrated in new research
published in The Journal of Experimental Medicine(1),(4),(6).
The success in treating CAPS led Ilaris to be investigated also
in other rare diseases such as systemic juvenile idiopathic arthritis
(SJIA), or more common ones such as some forms of gout, chronic
obstructive pulmonary disorder (COPD), rheumatoid arthritis and type
2 diabetes(4),(6), (8),(9).
The Novartis research and development strategy for Ilaris
involves using proof-of-concept studies which are small-scale Phase I
clinical trials in genetically well-defined diseases to determine how
genes interact in molecular or 'signaling' pathways(10). The
resulting clinical and biomarker data are then subjected to
state-of-the-art modeling and simulation to yield new insights into
the regulation of IL-1beta in patients(10).
"Ilaris is the outcome of our highly innovative approach to
research and development that is designed to bring more and better
targeted medicines to patients in the shortest possible time," said
Trevor Mundel, MD, Head of Global Development at Novartis Pharma AG.
"We are extremely excited about the efficacy shown by Ilaris in
patients with CAPS, and we hope to be able to extend these benefits
to many more patients with other inflammatory diseases which are more
widespread, and often equally debilitating."
CAPS comprises three syndromes of increasing severity: familial
cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS)
and neonatal-onset multisystem inflammatory disease (NOMID)(1),(2).
Patients with CAPS experience debilitating fatigue, fever and chronic
anemia from infancy(1),(2),(11). Inflammation can affect the skin,
eyes and bones causing rashes, conjunctivitis and destructive
arthritis(1),(2),(11). Other severe complications of CAPS include
progressive hearing loss, visual and intellectual impairment, and
amyloidosis, a condition in which the build-up of proteins can cause
vital organs to fail(1),(2),(3),(11). About 25% of CAPS patients
develop systemic amyloidosis resulting in renal failure, and usually
in death within five to 10 years(3).
The Phase III clinical trial in CAPS was a multinational,
randomized, double-blind and placebo-controlled study designed to
assess the efficacy, safety and tolerability of Ilaris(1). The
48-week study involved 35 patients aged nine to 74 years old and was
divided into three parts(1). First interim results were presented at
the American Rheumatology College meeting in October 2008(5), while
full one-year results are now published for the first time in The New
England Journal of Medicine(1).
In the first part of the study lasting eight weeks, 35 patients
received a single dose of Ilaris (150 mg by subcutaneous injection).
All but one patient (97%) showed a rapid and complete response(1).
After this, 31 patients who maintained their response proceeded to
part two, a randomized 24-week, double-blind placebo-controlled
phase. Patients were treated every eight weeks with either Ilaris or
placebo and if a relapse occurred, they entered part three.
Part two of the study included the primary endpoint, a comparison
between the number of patients treated every eight weeks with Ilaris
who experienced disease relapse or 'flares' vs. those on placebo.
Results showed that no patients in the Ilaris group experienced a
disease flare compared to 13 out 16 patients in the placebo group (0%
vs. 81%, p<0.001)(1).
Following either completion of part two or occurrence of a
disease flare, patients proceeded to part three which involved at
least two further doses of Ilaris for a minimum of 16 weeks. Out of
31 patients who entered part three, 28 completed this phase of the
study without suffering a relapse (90%)(1). One patient suffered a
relapse on the last day of the study, i.e. 62 days after receiving
their last dose of Ilaris(1). In addition, one patient discontinued
the study due to a perceived lack of therapeutic response, and one
discontinued because of a urinary tract infection(1).
Ilaris was generally well tolerated, with no consistent pattern
of adverse events beyond an increase in all suspected infections(1).
Two patients experienced serious adverse events but there were no
deaths or life-threatening adverse events during the study(1).
Ilaris has orphan drug status in the EU, US, Switzerland and
Australia for the treatment of CAPS and is currently under priority
review by the regulatory authorities in US, Switzerland and
Australia. Regulatory review is also underway in the EU. Orphan drugs
are those designed to treat serious or life-threatening diseases
affecting fewer than 200,000 people (in the US)(12) or fewer than
five out of 10,000 people (in the EU)(13). Ilaris has also been
granted orphan drug status for SJIA in the EU, Switzerland and in the
The foregoing release contains forward-looking statements that
can be identified by terminology such as "potentially," "being
investigated," "priority review," "may," "designed to," "hope to," or
similar expressions, or by express or implied discussions regarding
potential future regulatory filings or marketing approvals for Ilaris
or regarding potential future revenues from Ilaris. You should not
place undue reliance on these statements. 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 Ilaris to be materially
different from any future results, performance or achievements
expressed or implied by such statements. There can be no guarantee
that Ilaris will be approved for sale in any market, or for any
particular indication. Nor can there be any guarantee that Ilaris
will achieve any levels of revenue in the future. In particular,
management's expectations regarding Ilaris could be affected by,
among other things, unexpected regulatory actions or delays or
government regulation generally; unexpected clinical trial results,
including unexpected new clinical data and unexpected additional
analysis of existing clinical data; 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; the impact that the foregoing factors could
have on the values attributed to the Group's assets and liabilities
as recorded in the Group's consolidated balance sheet, 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.
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 2008, the Group's continuing operations achieved
net sales of USD 41.5 billion and net income of USD 8.2 billion.
Approximately USD 7.2 billion was invested in R&D activities
throughout the Group. Headquartered in Basel, Switzerland, Novartis
Group companies employ approximately 98,000 full-time-equivalent
associates and operate in more than 140 countries around the world.
For more information, please visit http://www.novartis.com.
1. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB et al. A
Randomized Trial of Canakinumab in Cryopyrin-Associated Periodic
Syndrome. NEJM. 2009.
2. K. L.W Durrant, R. Goldbach-Mansky, H. Hoffman, K.Leslie, B.
Rubin. CAPS Cryopyrin-Associated Periodic Syndromes 2008. Available
at: http://www.nomidalliance.net/Download1.html, last accessed
3. National Horizon Scanning Centre. Canakinumab for cryopyrin
associated periodic syndrome. November 2008. Available at: http://www
c/Canakinumab.pdf Accessed: 21.04.09
4. Alten R, Gram H, Joosten LA, et al. The human
anti-interleukin-1ss (IL-1ss) monoclonal antibody ACZ885 is effective
in joint inflammation models in mice and in a proof of concept study
in rheumatoid arthritis patients. Arthritis Res Ther 2008;10:R67.
5. Lachmann HJ, Kone-Paut I, Kümmerle-Deschner J et al. Efficacy
and safety of canakinumab (ACZ885), a fully human
anti-interleukin-1beta antibody, in cryopyrin associated periodic
fever syndrome: Results of a multicenter, randomized, double-blind,
phase III study. Poster presented at the American College of
Rheumatology 2008. 24-29 October. San Francisco, USA.
6. Lachmann HJ, Lowe P, Felix SD et al. In vivo regulation of
interleukin 1 in patients with cryopyrin-associated periodic
syndromes. J. Exp. Med. 2009. Published online April 13 2009.
Available at: http://www.jem.org/cgi/doi/10.1084/jem.20082481
7. Joost PH, Drenth MD, Jos W.M. van der Meer. The Inflammasome -
A Linebacker of Innate Defense. NEJM 2006. Vol 355:730-732. Number 7
8. Church LD, Cook GP, McDermott MF. Primer: inflammasomes and
interleukin 1ss in inflammatory disorders. Nat Clin Pract Rheumatol
9. Dinarello C.A. Blocking IL-1 in systemic inflammation. JEM
Vol. 201, No. 9, May 2, 2005 1355-1359
10. Novartis data on file
11. Kastner DL. Hereditary Periodic Fever Syndromes. Hematology
2005-American Society of Hematology Education Program. 2005:
12. Orphan Drug Act. US Food and Drug Administration. Section 526
(2), Line 2.
13. The orphan drug strategy. Europa: Gateway to the European
Union. Paragraph 1, Line 1.
[*]Tradename Ilaris (spelt: I-L-A-R-I-S) is subject to regulatory
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