Phase III data in The Lancet show Novartis siponimod significantly improved outcomes in patients with secondary progressive MS

EAST HANOVER, N.J., March 22, 2018 /PRNewswire/ -- Novartis today announced that the full results from the Phase III EXPAND study of oral, once-daily siponimod (BAF312) in secondary progressive multiple sclerosis (SPMS) were published in the peer-reviewed journal The Lancet. These pivotal results show siponimod significantly reduced the risk of three-month confirmed disability progression versus placebo (primary endpoint)¹. Siponimod also meaningfully delayed the risk of six-month confirmed disability progression and demonstrated favorable outcomes in other relevant measures of multiple sclerosis (MS) disease activity¹. If approved, siponimod would be the first disease-modifying therapy to delay disability progression in a large trial of typical SPMS patients, including many who had reached a non-relapsing stage and high level of disability¹.

SPMS is a form of MS that is associated with progressive, irreversible physical and cognitive disability, largely independent of relapses². Patients transition to SPMS after an initial phase of relapsing-remitting MS (RRMS), the most commonly diagnosed type of MS^3,4. There is a high unmet medical need for new treatments that are safe and effective for patients with SPMS⁵.

“Today’s published full EXPAND results show that siponimod can delay disability progression in typical established SPMS patients, where other approaches tested so far have been unsuccessful,” said Professor Ludwig Kappos, University Hospital Basel and Principal Investigator of EXPAND. “These data are all the more impressive when considering that the majority of patients had already advanced disability when starting treatment in EXPAND.”

Siponimod is an investigational selective modulator of specific subtypes of the sphingosine-1-phosphate (S1P) receptor⁶. Full data from EXPAND show that siponimod reduced the risk of three-month confirmed disability progression by a statistically significant 21% versus placebo (p=0.013); efficacy was overall consistent across pre-defined patient subgroups¹. Other clinically relevant endpoint data show that siponimod, when compared to placebo:

• Did not show a significant difference in the Timed 25-Foot Walk test, the first key secondary endpoint, and the MS Walking Scale¹
• Limited the increase of T2 lesion volume by approximately 80%, measured by volume change from baseline (mean over 12 and 24 months, p<0.0001), the second key secondary endpoint¹
• Reduced the risk of six-month confirmed disability progression by 26% (p=0.0058)¹
• Reduced annualized relapse rate (ARR) by 55% (p<0.0001)¹
• Slowed the rate of brain volume loss by 23% (relative difference; mean across 12 and 24 months, p=0.0002)¹
• Demonstrated a safety profile which was overall consistent with the known effects of S1P receptor modulation¹

“Novartis is dedicated to advancing MS research and pioneering solutions for people living with SPMS - a complex, debilitating disease,” said Danny Bar-Zohar, Global Head Neuroscience Development, for Novartis. “The pivotal EXPAND data provide patients, and the medical community alike, with hope that a much needed, safe and effective treatment option is on the horizon for SPMS, for which treatment options are scarce. We look forward to continuing to work with regulatory agencies to make siponimod available for these patients as fast as possible.”

Novartis plans to file for regulatory approval of siponimod for SPMS with the US Food and Drug Administration in early 2018. The EXPAND results have previously been presented at scientific congresses.

About the EXPAND Study
The EXPAND study is a randomized, double-blind, placebo-controlled Phase III study, comparing the efficacy and safety of siponimod versus placebo in people with SPMS^1,7. It is the largest randomized, controlled study in SPMS to date, and included 1,651 people with SPMS from 31 countries^1,8. At the time of the study, individuals enrolled in EXPAND had a mean age of 48 years and the mean times since first MS symptoms and conversion to SPMS were 17.1 (±8.4) and 3.9 (±3.6) years for siponimod and 16.2 (±8.2) and 3.6 (±3.3) years for placebo, respectively¹. They also had an Expanded Disability Status Scale (EDSS) score between 3.0 and 6.5 inclusive, with a median score of 6.0, which corresponds to the use of a unilateral walking aid (e.g., a cane or a crutch)^1,7. Patients were randomized to receive either 2mg siponimod once-daily or placebo, in a 2:1 ratio^1,7. Patients continued on siponimod treatment in the open-label long-term extension part of the study¹.

About Siponimod (BAF312)
Siponimod is an investigational selective modulator of specific subtypes of the sphingosine-1-phosphate (S1P) receptor⁶. The S1P receptor is commonly found on the surface of specific cells residing in the central nervous system (CNS), that are responsible for causing CNS damage that drives loss of function in SPMS.

About Multiple Sclerosis
MS is a chronic disorder of the CNS that disrupts the normal functioning of the brain, optic nerves and spinal cord through inflammation and tissue loss⁹. The evolution of MS results in an increasing loss of both physical (e.g., walking) and cognitive (e.g., memory) function. There are three main types of MS: relapsing-remitting MS (RRMS), SPMS and primary progressive MS (PPMS)⁴.

SPMS is characterized by gradual worsening of neurological function over time². This leads to a progressive accumulation of disability, largely independent of relapses, which can severely affect patients’ abilities to carry out everyday activities². It follows an initial phase of RRMS, which accounts for approximately 85% of all MS diagnoses; a quarter of people with RRMS will eventually go on to develop SPMS within 10 years of their initial RRMS diagnosis, rising to more than three-quarters after 30 years^3,10. There remains a high unmet need for effective and safe treatments to help delay disability progression in SPMS⁵.

MS affects around 400,000 people in the US¹¹.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. 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 provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2017, the Group achieved net sales of USD 49.1 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 122,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.

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 References 1. Kappos L, Cree B, Fox R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomized, phase 3 study. Lancet. Published online March 22, 2018. http://dx.doi.org/10.1016/S0140-6736(18)30475-6. 2. MS Society. Secondary Progressive MS (SPMS). https://www.mssociety.org.uk/what-is-ms/types-of-ms/secondary-progressive- spms. Accessed March 19, 2019. 3. Multiple Sclerosis International Federation. Atlas of MS 2013. http://www.msif.org/wp-content/uploads/2014/09/Atlas-of- MS.pdf. Accessed March 19, 2018. 4. Multiple Sclerosis Society. Types of MS. https://www.mssociety.org.uk/what-is-ms/types-of-ms. Accessed March 19, 2018. 5. Mehr S.R. and Zimmerman M.P. Reviewing the unmet needs of patients with multiple sclerosis. Am Health Drug Benefits. 2015; 8(6);426-431. 6. Gergely P et al. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol 2012; 167(5): 1035-47. 7. ClinicalTrials.gov. Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND). https://clinicaltrials.gov/ct2/show/NCT01665144?term=BAF312+expand&rank=1. Accessed March 19, 2018. 8. Kappos L et al. Baseline Subgroup Characteristics of EXPAND: A Phase 3 Study of Siponimod (BAF312) for the Treatment of Secondary Progressive Multiple Sclerosis (P3.084). Neurology. 2016; 86(16):suppl. P3.084. 9. PubMed Health. Multiple Sclerosis (MS). https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024311/. Accessed March 19, 2018. 10. Tremlett H, et al. The natural history of secondary-progressive multiple sclerosis. Mult Scler. 2008:14:314-324. 11. Tullman M. Overview of the epidemiology, diagnosis and disease progression associated with multiple sclerosis. Am J Managed Care. 2013 Feb;19(2 Suppl):S15-20. 

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