Despite only being a very small trial and with lingering questions over the primary endpoint, analysts were overall positive on Ultragenyx’s ($RARE) late-stage data for the incredibly rare genetic, metabolic disorder mucopolysaccharidosis 7.
The California biotech posted new data last night from the pivotal Phase III study of its experimental recombinant human beta-glucuronidase (rhGUS, UX003) in patients with mucopolysaccharidosis 7 (MPS 7).
This form of the condition, also known as Sly syndrome, affects typically young children and the more severe form of the disease significantly shortens life span.
It’s extremely rare, affecting only about one in one million births. Fewer than 100 cases have been reported in the U.S., with only 200 patients believed to have the condition worldwide.
There are 11 forms of MPS, with MPS 7 characterized by a deficiency of beta-glucuronidase--an enzyme required for the breakdown of the glycosaminoglycans (GAGs) dermatan sulfate, chondroitin sulfate and heparan sulfate--all critical components of many tissues.
The company said in a statement that its study--which was made up of 12 patients--met its primary endpoint of reducing urinary GAG excretion after 24 weeks of treatment. Data showed a reduction from baseline of 64.8% for this biomarker.
Analysts at Leerink were impressed, saying: “We are shocked at both the magnitude and the consistent reduction in uGAGs. Despite investors’ concerns of a small trial, 4 mg/kg rhGUS effectively demonstrated its efficacy as an enzyme in removing the accumulated substrate in MPS 7 pts.”
A secondary endpoint had problems, however, given its slightly too high P-value (p=0.0527). This was assessing the Multi-Domain Responder Index (MDRI) score at 24 weeks of treatment, which looks at elements such as the 6-minute walk test (6MWT), fatigue and clarity of vision.
The biotech said it showed an overall mean improvement (±SD) of +0.5 domains (±0.80), but just failed to meet statistical significance. Analysts at Jefferies however said that despite this, most patients “achieved improvement/stabilization.”
The firm added that a positive trend was shown in the 6MWT and fatigue--two areas it said caregivers identified as “the most impactful clinical problems.”
Jefferies said that a numeric increase of 20.8 metres in 6MWT was reported in 9 evaluable patients at 24 weeks, while three patients experienced significant improvement (+65/80/83m). But the remaining 6 showed a slight decline, around 7 meters less, according to the analysts’ data.
The company said it will be seeking submission to the EMA and the FDA in the first half of next year.
Jefferies said the Phase III trial “would likely support EU approval,” adding that although uncertainty remains, “clear uGAG reduction and positive trend in functional measurements may be sufficient for U.S. approval given rarity and heterogeneity of pts.”
Leerink echoed this sentiment, concluding that: “While the lack of a defined primary endpoint and the ultimate regulatory decision may keep some investors cautious, we are positively surprised on the improvements in such a small trial.”
There are a number of enzyme replacement therapies already on the market for other forms of the disease, namely: Sanofi/Genzyme’s ($SNY) MPS 1 Aldurazyme (laronidase); Shire’s ($SHPG) MPS 2 Elaprase (idursulfase); and BioMarin’s ($BMRN) MPS 4A Vimizim (elosulfase alfa), as well as its MPS 6 drug Naglazyme (galsulfase).
The occurrence of MPS and related diseases in the general population is thought to be one in 25,000 births, according to the MPS Society.
The biotech was down by 2.5% at close yesterday, but ticked up after hours by 2.3%.
- check out the Ultragenyx release
- read Leerink’s view (PDF)
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