New Medicines

MepseviiMucopolysaccharidosis VII (MPS VII - Sly disease)


New molecular entity

Development and Regulatory status

Licensed but not launched
May 22To the company ´s knowledge, there is only 1 patient diagnosed with MPS VII alive in the UK. And this patient is not treated with Mepsevii. There is an NHS England commissioning policy in development for Mepsevii, although this is specifically for the urgent neonatal cases initially [15].
Feb 20NICE have decided not to appraise Mepsevii for this indication due to the extreme rarity of MPS VII. The company still plans to make it available to eligible patients in the UK [14].
Nov 19In order to successfully commercialise Mepsevii, Ultragenyx is building a commercial infrastructure in Europe. It is taking certain precautionary measures with respect to Brexit and its impact to the EU, and will continue to monitor the situation. Expect this is a factor delaying launch in the UK [13].
Sep 19Launched in Germany [12].
Aug 18Mepsevii has been available in the US since Dec 17 [11].
Aug 18The EC has approved the Marketing Authorization Application (MAA) for Mepsevii™ (vestronidase alfa), for the treatment of non-neurological manifestations of Mucopolysaccharidosis VII (MPS VII; Sly syndrome) [10].
Jun 18Recommended for EU approval by CHMP - the full indication is "for the treatment of non-neurological manifestations of Mucopolysaccharidosis VII (MPS VII; Sly syndrome).” It is proposed that treatment with vestronidase alfa should be supervised by a healthcare professional experienced in the management of patients with MPS VII or other inherited metabolic disorders [9].
Nov 17Approved in US with launch expected later this month; EU decision expected H1 2018. Ultragenyx predict an average cost of $375,000 per patient per year after discounts [7,8].
Jun 17Filed in the US and granted priority review with a target action date of 16th November 2017 [6].
Jun 17Filed in the EU via the centralised procedure [5].
Feb 17Ultragenyx intend to submit EU and US marketing authorisation applications late 2017 [4].
Feb 17Ultragenyx has met with the FDA and EMA to discuss plans for regulatory fillings. In EU, the primary endpoint is the percent reduction in urinary glycosaminoglycans (GAG) excretion after 24 weeks of treatment. The EMA indicated that a trend in improvement in clinical endpoints would also be necessary for approval. In the US, there is no primary endpoint declared; the FDA will consider the totality of data on a per-patient basis [2].


Recombinant human beta-glucuronidase (rhGUS) enzyme replacement therapy. MPS VII is a genetic disorder characterised by a deficiency of beta-glucuronidase, leading to progressive accumulation of toxic glycolipids in various tissues and organs.
In the UK, Sly Disease is the rarest MPS with an average of only one baby every 10 years born with the condition. Worldwide it is estimated to have a frequency of less than 1:250,000 births. In its most extreme form, children are born with a condition called hydrops fetalis. Babies with hydrops fetalis rarely survive beyond a few weeks to a few months of age. Many individuals with Sly Disease are less severely affected and have clinical symptoms similar to other MPS [1].
Mucopolysaccharidosis VII (MPS VII - Sly disease)
Intravenous infusion

Trial or other data

Jul 16Ultragenyx reports positive top-line results from a pivotal PIII trial (UX003-CL301; NCT02230566). Patients were randomised to one of four cohorts, in which one cohort begins UX 003 therapy immediately, while the other three cohorts will receive placebo. Patients were dosed with 4 mg/kg of UX 003 every other week for up to 48 weeks. Prior to trial initiation, the development plan for UX 003 was discussed with the US FDA and EMA, and the EMA agreed on a single pivotal trial in 12 patients with MPS VII using a uGAG (urinary glycosaminoglycan) surrogate endpoint [2].
Oct 15Ultragenyx initiates a PIII extension study to assess long-term safety and efficacy of UX 003 in patients with MPS VII (NCT02432144; UX003-CL202). The endpoints of the study will be safety and efficacy of UX 003 at 144 weeks. Recruitment of approximately 20 patients is ongoing in the US, and is expected to expand to Brazil [2].
Jul 15PII study to assess safety and efficacy of UX 003 in paediatric patients with MPS VII starts (NCT02418455; UX003-CL203). The primary endpoint of the study is the reduction in urinary GAG excretion following 48 weeks of treatment. Approximately 7 patients, aged under five years old, will be enrolled in the US. The study may also include patients with non-immune hydrops fetalis. Interim data is expected by the end of 2016 [2].
Nov 14PIII study starts (NCT02230566). It will use a novel randomized, intra-subject placebo-controlled, single crossover design, referred to as Blind Start, to evaluate the safety and efficacy of UX003. 12 patients will be enrolled in the US. Primary outcome data is due to be collected by May 16 [3].
Dec 13Ultragenyx initiates an open-label, single-group PI/II trial to investigate safety and efficacy of UX 003 in the treatment of MPS VII (15258; MCRN2476; UX003CL201; NCT01856218). Approximately 5 male patients, aged 5 to 30 years will be enrolled in the UK. Patients will be dosed every second week for 36 weeks, with an optional continuation period of up to further 36 weeks [2].

Evidence based evaluations