Novartis meddelar att de lämnat in registreringsfilen för siponimod till EMA och FDA

Novartis meddelar att de lämnat in registreringsfilen för siponimod till EMA och FDA

Siponimod är en endos tablettbehandling för behandling av sekundärprogressiv MS hos vuxna. För att få en skyndsam registrering av produkten har Novartis använt sig av en ”priority review voucher”.

More than 80% of people with relapsing-remitting MS (RRMS) – the most common form of the condition at diagnosis – go on to develop SPMS, with or without relapses[2],[3]. SPMS is a form of MS that leads to progressive, irreversible disability, such as the need for enhanced walking aids and wheelchairs, bladder dysfunction and cognitive decline, largely independent of relapses. Following the initial RRMS course, there is a gradual increase in the number of patients transitioning to SPMS, with around 25% progressing by 10 years post-onset, 50% by 20 years and more than 75% by 30 years[2],[3].

”We are excited to see a potential new treatment on the horizon,” said Bruce Bebo, Executive Vice President Research, National MS Society, United States. ”It is a significant milestone in our unrelenting search for treatments that can benefit adults living with secondary progressive MS who currently have few options.”

”Siponimod is the first investigational medicine to show a significant delay in disability progression in typical SPMS patients,” said Paul Hudson, Chief Executive Officer, Novartis Pharmaceuticals. ”With siponimod, we underpin our strong commitment to the MS community by reimagining care for people whose lives have been considerably disrupted by this devastating illness. We are closely working with the FDA and EMA to ensure siponimod is available for patients as soon as possible.”

The regulatory application is based on data from the EXPAND study, a randomized, double-blind, placebo-controlled Phase III study, comparing the efficacy and safety of siponimod versus placebo in people living with typical SPMS. At study initiation, more than 50% of patients in the EXPAND study relied on a walking aid[1]. Results from the pivotal study showed siponimod significantly reduced the risk of three-month confirmed disability progression versus placebo (primary endpoint; 21% versus placebo, p=0.013). Siponimod also meaningfully delayed the risk of six-month confirmed disability progression (26% vs placebo, p=0.0058) and demonstrated favorable outcomes in other relevant measures of MS disease activity and progression[1]. Further, more advanced analyses of the EXPAND study showed that siponimod reduced the risk of disability progression largely disassociated from relapses (three-month disability progression, range 14-20%; six-month disability progression 29-33%)[1].

In addition, Novartis conducted the BOLD study, a randomized, double-blind, placebo-controlled, adaptive dose-ranging, Phase II study in patients with RRMS. The study showed that siponimod significantly reduced the annualized rate of relapses (ARR) over six months compared to placebo (ARR siponimod 2 mg vs. placebo 0.20 vs. 0.58 (p=0,041))[4].

In Switzerland, Swissmedic granted fast track authorization procedure for siponimod in SPMS. Discussions with additional health authorities regarding siponimod are ongoing.

About Siponimod (BAF312)
Siponimod is an investigational, selective modulator of specific subtypes of the sphingosine-1-phosphate (S1P) receptor[5]. Siponimod binds to the S1P1 sub-receptor on lymphocytes, which prevents them from entering the central nervous system (CNS) of patients with multiple sclerosis. This leads to the anti-inflammatory effects of siponimod.[1] Siponimod also enters the CNS and binds to the S1P5 sub-receptor on specific cells in the CNS (oligodendrocytes and astrocytes)[6]. By binding to these specific receptors, siponimod has the potential to modulate damaging cell activity, and preclinical studies suggest that it may prevent synaptic neurodegeneration and promote remyelination in the CNS[7].

[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.
[2] Multiple Sclerosis International Federation. Atlas of MS 2013. Accessed October 2018.
[3] Tremlett H, et al. The natural history of secondary-progressive multiple sclerosis. Mult Scler. 2008:14:314-324.
[4] Selmaj K, et al. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet Neurol. 2013;12(8):756-67.
[5] 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.
[6] Tavares A, et al. Brain distribution of MS565, an imaging analogue of siponimod (BAF312), in non-human primates. Neurology. 2014;82(10):suppl. P1.168.
[7] Gentile A, et al. Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis. Journal of Neuroinflammation 2016;13(1):207.
[8] PubMed Heath. Multiple Sclerosis (MS). Accessed October 2018.
[9] Tullman M. Overview of the epidemiology, diagnosis and disease progression associated with multiple sclerosis. Am J Managed Care. 2013;19(2 Suppl):S15-20.
[10] Multiple Sclerosis Society. Types of MS. Accessed October 2018.