Novartis MS portfolio presence at 28th ECTRIMS

New data will be presented at the 28th annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) from the Novartis Multiple Sclerosis (MS) portfolio on the growing clinical trial and real-world experience with Gilenya® (fingolimod), the first once-daily oral therapy approved to treat people with relapsing forms of MS. In addition, new data will be presented on investigational compounds BAF312 (siponimod) and AIN457 (secukinumab).

“Along with new data reinforcing the efficacy and safety profile of once-daily oral Gilenya, we’re pleased to present positive results at ECTRIMS for our investigational MS compounds BAF312 (siponimod) and AIN457 (secukinumab),” said Betsy Garofalo, Global Head Neuroscience Development Franchise, Novartis Pharma AG. “The data being presented at ECTRIMS underscores the depth and breadth of our MS portfolio and our ongoing commitment to addressing unmet patient needs in MS.”  

Extensive Gilenya data will be presented at ECTRIMS, demonstrating high efficacy across clinical and MRI measures, real-world tolerability and adherence and a safety profile generally consistent with pivotal studies.

Results from the BAF312 (siponimod) Phase II BOLD study in relapsing-remitting MS (RRMS) will also be presented. In addition, pre-clinical data will be presented demonstrating that BAF312 reaches the central nervous system (CNS), with the potential for direct CNS effects that may be relevant for treatment of secondary-progressive MS (SPMS).(1) These data support the move to a Phase III study of BAF312 in SPMS starting later this year. SPMS is a sub-type of MS where there are limited treatment options. The vast majority (85%) of people with relapsing-remitting MS will transition to SPMS; 50% within ten years and 90% within 25 years.(2)

There will also be a presentation in the late-breaking session on the investigational compound, AIN457 (secukinumab). This presentation, “Positive proof of concept of AIN457, an antibody against interleukin-17A, in relapsing-remitting multiple sclerosis” will take place on Saturday, 13 October at 09:00 CET.

In addition, onsite at the Lyon Convention Center there will be a Novartis symposium, “Growing global experience with once-daily oral fingolimod in MS,” taking place on Wednesday 10 October, 18:30 – 19:30 CET. There will also be a number of interactive “MS Innovation Exchanges,” an opportunity for healthcare professionals to learn about brain atrophy in MS, role of real-world data in assessing MS treatments and the importance of compliance and adherence in MS. Healthcare professionals should visit the Novartis booth for more information.

Novartis MS portfolio highlights at ECTRIMS include:

• Gilenya (fingolimod)
• Early effect of fingolimod on clinical and MRI related outcomes in relapsing multiple sclerosis (Poster 459,Chin: Thursday 11 October 2012; 15:30 and 17:00 CET)
• Fingolimod reduces magnetic resonance imaging inflammatory lesion activity versus placebo in patients with relapsing–remitting multiple sclerosis: Results from the Phase III FREEDOMS II study (Poster 724,Radue: Friday 12 October 2012; 15:30 and 17:00 CET)
• Long-term safety of fingolimod in relapsing multiple sclerosis: Update to integrated analyses of phase 2 and 3 studies and extension phases (Poster 983, Cohen: Friday 12 October 2012; 15:30 and 17:00 CET)
• Long-term comparison of fingolimod with interferon-beta-1a: results of 4.5-year follow-up from the extension phase III TRANSFORMS study (Poster 517, Montalban: Thursday 11 October 2012; 15:30 and 17:00 CET)
• Phase III FREEDOMS study extension: long-term safety of fingolimod (FTY720) in relapsing-remitting multiple sclerosis (Poster 523, O’Connor: Thursday 11 October 2012; 15:30 and 17:00 CET)
• Fingolimod treatment initiation experience: cardiac and holter electrocardiogram findings from three phase 3 studies (Poster 530, DiMarco: Thursday 11 October 2012; 15:30 and 17:00 CET)
• Study design and first interim results of a registry study to establish long-term safety and pharmaco-economic data on fingolimod (Gilenya®) in multiple sclerosis patients in Germany (PANGAEA). (Poster 522, Ziemssen: Thursday 11 October 2012; 15:30 and 17:00 CET)
• Comparison of time to discontinuation among multiple sclerosis patients receiving fingolimod and other first-line disease-modifying treatments (Poster 717,Agashivale: Friday 12 October 2012; 15:30 and 17:00 CET)
• Trial design and baseline data of the INFORMS (fingolimod in patients with primary progressive multiple sclerosis) study (Poster 951, Polman: Friday, 12 October 2012; 15:30 and17:00 CET)

Siponimod (BAF312) treatment leads to early MRI benefits in relapsing-remitting multiple sclerosis patients: Results from a phase 2 study (Poster 494, Li: Thursday 11 October 2012; 15:30 and17:00 CET)

Siponimod (BAF312) (and/or its metabolites) penetrates into the CNS and distributes to white matter areas (Poster 792, Aslanis: Friday, 12 October 2012; 15:30 and17:00 CET)

Positive proof of concept of AIN457, an antibody against interleukin-17A, in relapsing-remitting multiple sclerosis (Oral presentation 168, Havrdová: Parallel Session 13 “Late Breaking News”, Saturday, 13 October 2012, 09:00 CET)

Gilenya, licensed from Mitsubishi Tanabe Pharma Corporation, is the first in a new class of compounds called sphingosine 1-phosphate receptor (S1PR) modulators. It has demonstrated superior efficacy compared to Avonex®, a commonly prescribed treatment, showing a 52% relative reduction in annualised relapse rate (primary endpoint) and a 40% relative reduction in the rate of brain atrophy (secondary endpoint) at one year in a pivotal head-to-head trial in patients with relapsing-remitting multiple sclerosis.(3) In a recent sub-analysis, Gilenya showed a 61% relative reduction in annualised relapse rate compared to interferon-beta-1a (IM) at one year in subgroups of patients with highly active relapsing-remitting MS not responding to interferon treatment.(4)

Gilenya is generally a highly effective once-daily oral MS treatment. In clinical trials it was generally well tolerated with a manageable safety profile. There is increasing experience with Gilenya providing data on long-term effectiveness and safety, with approximately 49,000 patients treated in clinical trials and in a post-marketing setting.(5) Currently, there has been approximately 52,000 patient years of exposure5. In clinical trials, the most common side effects were headache, liver enzyme elevations, influenza, diarrhoea, back pain, and cough. Other Gilenya-related side effects included transient, generally asymptomatic, heart rate reduction and atrioventricular block upon treatment initiation, mild blood pressure increase, macular edema, and mild bronchoconstriction.(3,6)

The rates of infections overall, including serious infections, were comparable among treatment groups, although a slight increase in lower respiratory tract infections (primarily bronchitis) was seen in patients treated with Gilenya. The number of malignancies reported across the clinical trial program was small, with comparable rates between the Gilenya and control groups.(3,6)

BAF312 (siponimod) is an investigational compound in the Novartis multiple sclerosis (MS) portfolio. BAF312 is an oral, selective modulator of the sphingosine 1 phosphate (S1P) receptor subtypes 1 and 5 (S1P1, 5R modulator) with a short half-life leading to relatively rapid washout (six days).(7) The short half-life allows for a rapid recovery of blood lymphocyte counts following treatment discontinuation.(7) In the Phase II BOLD study, BAF312 demonstrated a favourable safety and tolerability profile when an initial dose titration regimen was used at the start of treatment. The most common adverse events were headache, bradycardia, dizziness and nasopharyngitis.(2)

AIN457 (secukinumab) is a fully human monoclonal antibody that binds to, and neutralises the bioactivity of, human IL-17A. Both animal and human data provide evidence that IL-17 is implicated in the pathogenesis of RRMS.

1. Aslanis V. Siponimod (BAF312) (and/or its metabolites) penetrates into the CNS and distributes to white matter areas. Poster presented at ECTRIMS, Lyon, October 2012.
2. The National Multiple Sclerosis Society. http://www.nationalmssociety.org/about-multiple-sclerosis/relapsing-ms/secondary-progressive-ms-spms/index.aspx. Last accessed October 2012.
3. Cohen J. et al. Oral Fingolimod vs. Intramuscular Interferon in Relapsing Multiple Sclerosis. N Eng J Med. Vol.362 No.5, Feb 4, 2010;362:402-415.
4. Havrdová E. et al. Clinical outcomes in subgroups of patients with highly action relapsing-remitting multiple sclerosis treated with Fingolimod (FTY720): Results from the FREEDOMS and TRANSFORMS phase III studies. Poster presented at ECTRIMS, Amsterdam, October 2011.
5. Data on file.
6. Kappos L, et al. Placebo-Controlled Study of Oral Fingolimod in Relapsing Multiple Sclerosis. N Eng J Med. Vol.362 No.5, Feb 4, 2010; 362:387-401.
7. Gergely et al. The selective S1P receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate: translation from preclinical to clinical studies. BJPharmacol, May 30 2012