Shire's rare disease duo gain "Breakthrough" status

Two rare disease drugs from Shire have received Breakthrough Therapy Designation from the US regulator.

Shire said the US Food and Drug Administration granted the designation for SHP621 (budesonide oral suspension or BOS) for eosinophilic oesophagitis (EoE), an inflammatory condition of the oesophagus and SHP625 (maralixibat) for the liver disease progressive familial intrahepatic cholestasis.

Shire earlier this month completed its $32 billion merger with Baxalta, establishing itself as a major force in drugs for rare diseases.

Breakthrough Therapy Designation means the FDA will give intensive guidance, organisational commitment involving senior managers as well as the possibility for a rolling or priority review of a filing, to ensure patients get access to therapies as soon as possible, pending approval.

However Shire cautioned the designation does not guarantee the FDA will approve either drug and the time of any approval is uncertain.

The designation is granted to a therapy that is intended to treat a serious or life-threatening disease or condition, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over current standard of care.

BOS is a novel, topically active, oral viscous formulation of budesonide and is formulated specifically for EoE.

In an open-label clinical trial, orally administered viscous budesonide was more effective than nebulised or swallowed budesonide for improving oesophageal eosinophil counts and endoscopic findings in adults with a new diagnosis of EoE.

The “Breakthrough” designation was granted based on data from a phase 2 trial in adults and adolescents with EoE.

Shire acquired maralixibat through its $260 million buyout of Lumena in 2014. But since then Shire has terminated its buyout package with a $90m payoff, after the drug failed in phase 2 in the rare genetic disorder Alagille syndrome last year.

But Shire is still trialling maralixibat in several rare liver diseases in children and adults. Preclinical models suggest it is a potent, selective inhibitor of the apical sodium-dependent bile acid transporter (ASBT).

ASBT inhibitors are designed to block bile acid reabsorption in the ileum and increases faecal bile acid excretion. Shire is developing maralixibat as an oral solution formulation for paediatric indications. It has been granted orphan status in the US and EU.