Event – Ultragenyx looks to data from its biggest projects


Ultragenyx is expecting phase II readouts from its two most valuable projects in the second half of the year: KRN23 in a rare metabolic bone disorder and UX007 in a genetic energy disorder. As orphan drugs these are potentially big money-makers for the company.

Interim results for both have shown positive trends, and these latest readouts will provide sounder conclusions on efficacy.


40-week results from 52 paediatric patients with X-linked hypophosphataemia (XLH) are expected by mid-2016. The open-label phase II study will report safety and efficacy data including rickets scores; also expected are 64-week results, including height growth velocity, from a subset of patients.

XLH is caused by high levels of the FGF23 hormone, which represses the reabsorption of phosphate from the urine, and the resulting loss of phosphate leads to poor bone growth and mineralisation. KRN23 is an anti-FGF23 monoclonal antibody and has orphan drug designation in the US.

Last year, interim phase II results showed increases in serum phosphorus in all 36 patients at 16 weeks. There was also substantial reduction in bone disease. The bi-weekly dose regimen resulted in better overall response than monthly dosing.

Ultragenyx and its partner, Kyowa Hakko Kirin, plan to file for conditional marketing approval towards the end of the year. Meanwhile a phase III study in paediatric XLH patients is expected to start in mid-2016, and will likely use RGI-C (radiographic global impression of change) as the primary endpoint and include a standard of care reference arm.

This is expected to be required for potential approval in the US, and could serve as a confirmatory study in the EU. A phase III study in adults is also recruiting.


Meanwhile, 78-week data from a phase II study of UX007 in long-chain fatty acid oxidation disorders (LC-FAOD) are expected in the second half of 2016. Baseline rates of major medical events, such as hypoglycaemia and cardiac events, will be compared against those approximately 18 months after UX007 treatment. A phase III trial is expected to start next year.

LC-FAOD are a group of autosomal recessive genetic disorders in which the body is unable to convert long-chain fatty acids into energy. A severe depletion of glucose in the body leads to serious liver, muscle and heart disease that can result in hospitalisations or early death. Despite treatment with low fat/high carbohydrate diets and supplements many patients continue to have significant metabolic events.

UX007 is a form of triheptanoin, a synthetic triglyceride used to increase substrates for energy-generating processes. It has orphan drug designation in the US and EU.

Last year, interim results from a single-arm open-label phase II study were released: 29 paediatric and adult patients evaluated at 24 weeks showed positive trends in efficacy data, including cycle ergometry and 12-minute walk test, but there was high variability among patients.

Treatment-related adverse events occurred in 62% of patients, with the most common being diarrhoea, abdominal or gastrointestinal pain and vomiting.


UX007 is forecast to become Ultragenyx’s biggest product, with sales set to reach $642m by 2022, according to sellside consensus from EvaluatePharma, and an NPV of $1.1bn, 46% the company’s market cap. KRN23, the company’s next-biggest asset, is expected to make $532m in 2022, equivalent to an $891m NPV.

Since its float at the beginning of 2014 Ultragenyx has risen 49%, climbing last July when interim data for KRN23 were released, giving the company an opportunity for a secondary offering, which raised a welcome $287m.

But since the beginning of this year the shares, which peaked at $132 in July 2015, have returned to around $60. The company is not expected to generate revenue until at least next year, and will be hoping that the upcoming data readouts rally shares. The $536m of currently on the balance sheet should, however, give it breathing space until then.

Project Trial ID
KRN23 NCT02163577
UX007 NCT01886378

To contact the writer of this story email Joanne Fagg in London at joannef@epvantage.com or follow @JoEPVantage on Twitter

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