A New Drug from Novartis drug Gilenya (fingolimod)

Novartis will showcase data from 13 abstracts on fingolimod (Gilenya®), at the 5th Joint Triennial Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) taking place from 19-22 October in Amsterdam.

The data being presented for fingolimod at ECTRIMS/ACTRIMS highlight the Novartis clinical trial program for sphingosine 1-phosphate receptor (S1PR) modulators. Fingolimod targets MS via effects on the immune system and new pre-clinical data to be presented at ECTRIMS/ACTRIMS supports an additional potential direct effect on the central nervous system (CNS)[1,2], although the clinical relevance of this remains to be determined. Additional clinical data describe efficacy in subgroups of patients with highly active disease in the pivotal Phase III studies.

"Gilenya has already demonstrated significant efficacy in large scale clinical trials which is reinforced by these important data presented at ECTRIMS/ACTRIMS reflecting different patient populations in need of a new treatment," said David Epstein, Head of the Pharmaceuticals Division at Novartis Pharma AG. "These findings will help further solidify the role of Gilenya in the treatment of MS within its approved indication."

Data highlights include: Fingolimod 0.5 mg significantly reduced annualized relapse rates (ARR) by up to 71% (from 61% to 71%) compared to interferon beta-1a IM and compared to placebo in relapsing-remitting multiple sclerosis (MS) patients with high disease activity despite previous MS disease-modifying treatment. Although the reduction in ARR in another subgroup of patients, those patients with rapidly evolving severe relapsing-remitting MS, was directionally consistent with other subgroup data, statistical significance was not achieved compared to interferon beta-1a IM due to the small number of patients in this subgroup[3]. (Abstract P473)

• In relapsing-remitting MS patients with high disease activity despite previous MS disease-modifying treatment, the relative reduction of ARR ranged from 61% compared to interferon beta-1a in TRANSFORMS to 62%-71% compared to placebo in FREEDOMS.
• In the European Union, Gilenya 0.5 mg is approved for the treatment of relapsing-remitting MS in patients with high disease activity despite treatment with interferon beta, and in patients with rapidly evolving severe relapsing-remitting MS.

Fingolimod 0.5 mg reduced the rate of brain atrophy, or brain volume loss, compared to interferon beta 1a IM over 12 months, irrespective of disease activity prior to study start as shown in an analysis of the pivotal Phase III TRANSFORMS study[3]. (Abstract P907)

A five year Phase II study extension showed that patients with relapsing MS treated with fingolimod maintained low disease activity with a safety profile consistent with that seen in other fingolimod clinical trials. Of the original 281 patients at the start of the Phase II study, approximately 50% (140 patients) completed five years of treatment[4]. (Abstract P978)

In addition to the data presentations, onsite at the RAI Exhibition and Conference Centre there will be a Novartis symposium, 'Fingolimod: pioneering innovation in MS treatment', taking place on Friday 21st October, 12:45 - 13:45 CET. There will also be three interactive 'MS Innovation Exchanges,' including two October 20 and one on October 21. The 'MS Innovation Exchanges' are an opportunity for healthcare professionals to learn about innovations in patient care, neuroimaging and patient outcomes. Healthcare professionals should visit the Novartis booth for more information. In addition, a press briefing will be taking place on Friday, October 21 from 15:30-17:00 CET.

About Gilenya® (fingolimod)
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® (interferon-beta-1a IM), a commonly prescribed treatment, showing a 52% relative reduction in annualized 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[5].

Gilenya is generally a highly effective once-daily oral MS treatment without label restrictions specific to treatment duration. In clinical trials it was generally well tolerated with a manageable safety profile, and there is increasing experience of Gilenya's long-term effectiveness and safety profile, with more than 25,000 patients having been treated as of mid October 2011 in clinical trials and in a post-marketing setting. Currently, there is more than 20,000 patient years of exposure[6]. In clinical trials, the most common side effects were headache, liver enzyme elevations, influenza, diarrhea, 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[5,7].

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[5,7].

The following key Novartis data will be presented during the ECTRIMS/ACTRIMS congress:

1. Abstract P473: Clinical and magnetic resonance imaging outcomes in subgroups of patients with highly active relapsing-remitting multiple sclerosis treated with fingolimod (FTY720): results from the FREEDOMS and TRANSFORMS phase 3 studies

2. Abstract P907: Fingolimod (FTY720) reduces brain volume loss over 12 months compared with intramuscular interferon beta-1a: subgroup analyses of TRANSFORMS data based on inflammatory disease activity

3. Abstract P320: A controlled study on the effect of fingolimod (FTY720) on the immune response following seasonal influenza vaccination and tetanus toxoid booster injection in patients with Multiple Sclerosis

4. Abstract P369: Brain distribution of BZM055, an imaging analog of fingolimod (FTY720), in non-human primate

5. Abstract P978: Long-term fingolimod (FTY720) in relapsing MS: 5-year results from an extension of a phase II, multicenter study show a sustained low level of disease activity

6. Abstract P239: Effect of fingolimod (FTY720) on disability progression: Application of a transition model to EDSS data collected in the FREEDOMS and TRANSFORMS trials

7. Abstract P494: Fingolimod (FTY720) modulates microglial activation to augment markers of remyelination

8. Abstract P930: Oral fingolimod (FTY720) in Japanese patients with relapsing multiple sclerosis: results of a 6-month, randomized, double-blind, placebo-controlled, phase 2 study

9. Abstract P460: Oral fingolimod (FTY720) in Japanese patients with relapsing multiple sclerosis: Results of a 12-month, phase 2 extension study

10. Abstract P961: Nervous system and immune system effects of sphingosine 1-phosphate receptor 5 deletion in mice alters experimental autoimmune encephalitis progression and the efficacy of fingolimod

11. Abstract P552: Treatment experience, burden and unmet needs (TRIBUNE) in multiple sclerosis study: patient preferences for MS treatments

12. Abstract P767: T-Cell response against varicella zoster virus in fingolimod treated patients with multiple sclerosis

13. Abstract P823: Sphingosine 1-phosphare receptor antagonists promote axonal ensheathment by human fetal oligodendrocyte progenitors

About Novartis
Novartis 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, eye care, cost-saving generic pharmaceuticals, consumer health products, preventive vaccines and diagnostic tools. Novartis is the only company with leading positions in these areas. In 2010, the Group's continuing operations achieved net sales of USD 50.6 billion, while approximately USD 9.1 billion (USD 8.1 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 121,000 full-time-equivalent associates and operate in more than 140 countries around the world.

1. Tamagnan G. et al. Brain distribution of BZM055, an imaging analog of fingolimod (FTY720), in non-human primate. Data Presented at ECTRIMS, Amsterdam, October 2011.
2. Noguchi K. et al. Nervous system and immune system effects of sphingosine 1-phosphate receptor 5 deletion in mice alters experimental autoimmune encephalitis progression and the efficacy of fingolimod. Data Presented at ECTRIMS, Amsterdam, October 2011.
3. 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. Data Presented at ECTRIMS, Amsterdam, October 2011.
4. Montalban X et al. Long-term fingolimod (FTY720) in relapsing MS: 5-year results from an extension of a phase II, multicenter study show a sustained low level of disease activity. Data Presented at ECTRIMS, Amsterdam, October 2011.
5. Cohen J. et al. Oral Fingolimod vs. Intramuscular Interferon in Relapsing Multiple Sclerosis. N Eng J Med. 2010; 362:402-415.
6. Novartis data on file.
7. Kappos L, et al. Placebo-Controlled Study of Oral Fingolimod in Relapsing Multiple Sclerosis. N Eng J Med. 2010; 362:387-401.