Data published today in The New England Journal of Medicine show that patients experienced a benefit within hours of receiving a dose of Ilaris, and only needed further treatment every two months to control their disease. The primary objective of the study was the proportion of patients with disease flare on Ilaris compared to placebo during the second part of the three part study, which was the 24-week double-blind period. Results showed that none of the patients in the Ilaris group experienced a disease flare compared to 13 out of 16 patients in the placebo group (0% vs. 81%, p<0.001).
“It is remarkable to see patients with a rare and debilitating disease respond so completely,” said study investigator Kieron S. Leslie, MD, Assistant Clinical Professor, Department of Dermatology at University of California School of Medicine in San Francisco. “Sustained response and convenient dosing, once every eight weeks, may give canakinumab a clinical advantage over current therapies in this area of high unmet medical need.”
CAPS includes a number of lifelong diseases that are associated with a gene mutation and characterized by the overproduction of interleukin 1-ß (IL-1ß), a protein (or cytokine) that plays a key role in driving inflammation. The clinical benefits of Ilaris, a fully human monoclonal antibody, previously known as ACZ885, are probably due to its highly innovative mechanism of action. Ilaris is a potent and selective IL-1ß blocker and works by attaching itself to IL-1ß for a sustained period, neutralizing it and therefore blocking inflammation and its related symptoms.
The success of Ilaris in treating CAPS has led to the investigation of its potential use 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.
The Novartis development strategy for Ilaris involves using proof-of-concept (PoC) studies or small-scale Phase I clinical trials in well-defined diseases or small patient populations to study the way genes interact through molecular or ‘signaling’ pathways. 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-1ß in patients.
“Our understanding of the underlying molecular basis of CAPS has enabled us to develop a very specific and targeted therapy for effective treatment of these patients,” said John Orloff, MD, Senior Vice President, US Medical and Drug Regulatory Affairs, Novartis Pharmaceuticals Corporation. “Since we know we can use Ilaris to block the actions of interleukin-1-beta based on the successful development program in CAPS, we can now begin to explore its potential to treat patients living with more common inflammatory diseases that may also be mediated by interleukin-1.”
CAPS is comprised of three syndromes that represent a spectrum of increasing severity, including familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID), with debilitating symptoms and limited treatment options. Patients with CAPS experience fatigue, fever and chronic anemia from infancy. Inflammation can affect the skin, eyes and bones or joints causing rashes, conjunctivitis and destructive arthritis. 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 fail2C. About 25% of CAPS patients develop systemic amyloidosis resulting in renal failure.
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. The 48-week study involved 35 patients, aged nine to 74 years old, and was divided into three parts. Results for study part two were presented at the American Rheumatology College meeting in October 2008, while the overall results are published for the first time in The New England Journal of Medicine.
In the first part, lasting eight weeks, 35 patients received a single dose of Ilaris 150 mg by subcutaneous injection. All but one patient (97.1%) showed a rapid and complete clinical response. Thirty-one patients (89%) 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 discontinued and entered part three.
Part two of the study included the primary endpoint: a comparison between the proportion of patients treated every eight weeks with Ilaris who experienced disease relapse or ‘flares’ vs. those on placebo. By the end of part two, results showed that none of the patients in the Ilaris group experienced a disease flare compared to 13 out of 16 patients in the placebo group (0% vs. 81%, p<0.001).
Following either completion of part two or occurrence of a disease flare, patients proceeded to part three which was open-label, and involved at least two further doses of Ilaris for a minimum of 16 weeks. Out of 31 patients who entered part three, 29 patients completed the study (94%). Clinical and biochemical remission of CAPS was sustained in 97 % patients who completed part 3 (28 out of 29). One patient suffered a relapse on the last day of the study, i.e. 62 days after receiving their last dose of Ilaris. In addition, one patient discontinued the study due to a perceived lack of therapeutic response, and one discontinued because of a serious urinary tract infection.
Ilaris was generally well tolerated, with no consistent pattern of adverse events emerging beyond an increase in all suspected infections. The most common adverse events reported by patients treated with Ilaris were nasopharyngitis and rhinitis. Two patients experienced serious adverse events, comprising, respectively, a lower urinary tract infection, and an episode of vertigo accompanied by acute closed angle glaucoma attributed to CAPS. This patient discontinued the study due to an unsatisfactory therapeutic effect. There were no deaths or life-threatening adverse events during the study.
Ilaris has orphan drug designation in the EU, US, Switzerland and Australia for the treatment of CAPS and its approval is currently under review by the regulatory authorities in these countries. Orphan drugs are those developed to treat diseases affecting fewer than 200,000 people (in the US) or fewer than five out of 10,000 people (in the EU). Ilaris has also been granted orphan drug designation for SJIA in the EU and the US.
Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as “potentially,” “potential,” “priority review,” “may,” “can,” 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. Nor can there be any guarantee that Ilaris will achieve any particular 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 Novartis 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.
About Novartis
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG which 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, preventive vaccines, diagnostic tools, cost-saving generic pharmaceuticals 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 96,700 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.
