MayzentSecondary progressive, relapsing and non-relapsing multiple sclerosis (MS)
New molecular entity
Development and Regulatory status
Dec 20NHS England communication for providers that patients being considered for siponimod will need to have a CYP2C9 test prior to starting treatment. This is funded by Novartis as this service is not routinely available on the NHS. Each hospital can access this via MayzentConnect after completing the relevant documentation. Viapath Analytics LLP are the accredited service provider. The samples will be tested at the Viapath labs at Guys & St Thomas’ .
Apr 20Available in the UK .
Jan 20Approved in EU .
Nov 19Recommended for EU approval by CHMP - the full indication is "treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity (see section 5.1)”; it is proposed that the drug be prescribed by physicians experienced in the treatment of multiple sclerosis .
Jun 19In the US, the Institute for Clinical and Economic Review concludes siponimod (Mayzent) is not cost effective at its current list price .
Mar 19Planned filing 2019 or later .
Mar 19Approved in the US for the treatment of adults with relapsing forms of multiple sclerosis, including secondary progressive multiple sclerosis (SPMS) with active disease, relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS). List price will be $88,500 per year [14,15].
Oct 18Both the FDA and EMA have accepted the New Drug Application (NDA) and Marketing Authorization Application (MAA) respectively, for siponimod (BAF312) .
Apr 18Novartis has initiated the submission of siponimod for US approval in SPMS in the first half of 2018. Filing for EU approval is planned to follow later in 2018 .
Jun 17Filings planned for 2018 .
Mar 17Estimated launch brought forward due to positive trial results.
Aug 16Filings to treat SPMS still planned for 2019 .
Mar 14Planned filing > 2018 .
Selective sphingosine 1-phosphate (S1P)-1 and -5 receptor modulator
Prevalence of MS in England is about 164 per 100,000 (Wales slightly lower, N. Ireland and Scotland higher). About 85% will have relapsing-remitting MS (RRMS) at onset but about 75% will eventually develop secondary progressive MS (about 50% within 10 years). In England, about 45% of those with MS have secondary progressive disease (about 40,000 patients) .
Secondary progressive, relapsing and non-relapsing multiple sclerosis (MS)
Trial or other data
Apr 20Five yr data from the EXPAND open-label extension trial assessed the long-term efficacy and safety of either continuing Mayzent or switching from placebo to Mayzent. Pts on who continued Mayzent were significantly less likely to experience 3 and 6-month confirmed disability progression (CDP) (p=0.0064 and p=0.0048, respectively) vs. the placebo switch group. There was also a 52% reduction in the annualised relapse rate (ARR) in the Mayzent group vs. the placebo switch group (p<0.0001). The risk of worsening of cognitive impairment at 6-months was reduced by 23% for the Mayzent group vs. placebo switch group (p=0.0014). The incidence of adverse events was consistent with the controlled treatment period1. This EXPAND open-label extension is ongoing for 7 years.
Sep 19New post hoc statistical analysis of the EXPAND study presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual congress. On average, patients taking siponimod went more than 4 years longer than those taking a placebo before needing to rely on a wheelchair. Further analyses demonstrated siponimod also significantly reduced grey matter volume loss at 1 and 2 years .
May 19Novartis announce a new analysis of the PIII EXPAND study, demonstrating that treatment with siponimod had a clinically meaningful positive impact on cognitive processing speed (CPS) in patients with SPMS. The data also show patients treated earlier in the course of their disease with less cognitive impairment benefited most from siponimod treatment vs placebo, suggesting early treatment is important to ensure better cognitive outcomes .
Oct 18There are few effective treatments to slow SPMS, and those available (interferon, mitoxantrone) are only effective when relapses are still occurring; they also require parenteral administration and in the case of mitoxantrone have significant toxicity. Demand for an effective oral therapy is likely to be considerable .
Mar 18PIII study (EXPAND) of oral, once-daily siponimod in secondary progressive multiple sclerosis (SPMS) published. Results found significantly reduced risk of three-month confirmed disability progression versus placebo (primary endpoint) and meaningfully delayed the risk of six-month confirmed disability progression and demonstrated favorable outcomes in other relevant measures of multiple sclerosis (MS) disease activity .
Sep 16Novartis releases updated data for siponimod which showed it can cut the risk of disability progressing by 21% when compared with placebo over three months .
Aug 16Novartis announces siponimod met the primary endpoint of a reduction in disability progression risk as compared to placebo in the 1,651-patient EXPAND trial. It didn’t disclose if the trial met secondary endpoints .
Jan 16PIII EXPAND (NCT01665144) is currently recruiting pts; now due to complete collection of primary outcome data in Aug 16 .
Jul 13NCT01665144 EXPAND (Exploring the efficacy and safety of siponimod in patients with Secondary Progressive Multiple Sclerosis, CBAF312A2304) is a multicenter, randomized, double-blind, placebo-controlled variable treatment duration study (anticipated range 23–42 months). 1530 individuals, aged 18–60 years with SPMS (EDSS score of 3.0–6.5) will be randomized. Treatment will start with a 6-day dose titration (0.25, 0.25, 0.5, 0.75, 1.25, 2mg) and continue at a dose of 2mg or placebo (2:1). The primary outcome is delay in the time to 3-month confirmed disability progression as measured by EDSS. The study has 90% power to detect a 30% reduction in the risk of 3-month confirmed disability progression (hazard ratio 0.70). Study will be stopped when 374 events (patients with progression) are observed. The study started in Dec 12 and is due to complete Sep 16 [1,2]