EU thumbs-up sets the stage for burosumab’s more important test

Today’s EU approval for Ultragenyx’s burosumab marks the first green light for this rare disease drug and sets the stage for a more important event: a US FDA decision, due in April, that should bring with it the company’s second priority review voucher.

Given the mixed data burosumab had generated, a positive verdict by the EMA – albeit on a conditional basis – bodes well given the US FDA’s arguably less stringent stance. While orphan drug pricing remains a contentious issue the EU regulator is showing itself to be favourably disposed; today also saw two other rare disease drugs recommended for approval.

These were Swedish Orphan Biovitrum’s aging rheumatoid arthritis drug Kineret, recommended for Still’s disease, and the established, off-patent diabetes drug glibenclamide, whose indication the EU’s CHMP is proposing to extend to neonatal diabetes mellitus, an extremely rare form of the disease that is diagnosed in the first six months of life.

Second approval

Burosumab, trademarked Crysvita in the EU, has become Ultragenyx’s second approved product, after the US green-lit the enzyme-replacement therapy Mepsevii for Sly syndrome last November.

That came with a priority review voucher that the group swiftly sold to Novartis for $130m. US approval of burosumab, a drug for treating X-linked hypophosphataemia, should yield another such voucher, and the expectation must be that the company will also seek to turn this into hard cash.

Today’s approval could yet be revoked: it is conditional on the outcome of three ongoing studies, whose results are to be submitted by 2020. Conditional approvals are granted where there is an overriding public health interest but insufficient clinical backing.

For Ultragenyx this is just as well: burosumab’s adult trial hit its primary efficacy measure but missed an important secondary endpoint looking at pain. The US burosumab filing seeks approval in adults as well as children, whereas the EU go-ahead is for children and adolescents only.

The EU approval is based on efficacy seen in a trial in 5-12 year-olds being extrapolated to children between the ages of one and four.

Meanwhile, the EU’s two positive recommendations will result in full approval extensions if they are adopted by the European commission.

Swedish Orphan’s Kineret is proposed for use in infants, children, adolescents and adults with Still’s disease, a rare condition that in the young includes systemic juvenile idiopathic arthritis.

Glibenclamide’s recommendation concerns a new formulation, trademarked Amglidia, put forward by the private French speciality pharma company Ammtek. Crushed up glibenclamide tablets are apparently already used off label to treat neonatal diabetes, a condition thought to involve distinct genetic mutations.

The EU’s positive stance might signal a turnaround for Ultragenyx after several clinical setbacks. And another project could also see a reversal of fortune: there had been doubts about triheptanoin, which failed in Glut1 deficiency syndrome, but hopes now rest on an early filing in another condition, long-chain fatty acid disorder.

To contact the writers of this story email Jacob Plieth or Madeleine Armstrong in London at [email protected] or follow @JacobPlieth or @ByMadeleineA on Twitter