Shire Hits Two Breakthrough for Rare Disease Treatment


Dublin based Irish company, Shire procured US FDA Breakthrough Therapy Designation for two experimental candidates- SHP621 and SHP625 for the treatment of rare gastrointestinal conditions-eosinophilic esophagitis (EoE) and progressive familial intrahepatic cholestasis type 2 (PFIC2) respectively.

shire dublin

The FDA Breakthrough status was the second good news that came to Shire this month, after it acquired Baxalta, a 2015 founded therapeutics developer for orphan disease in $32 billion, earlier this month.

The investigational candidate, SHP621 is a novel, budesonide oral suspension (BOS) indicated for the treatment of EoE. EoE is a recently identified rare, chronic, allergic condition which causes inflammation in the esophagus due to infiltration of the increased number of eosinophils (a type of white blood cells) into the epithelial lining of the esophagus that causes difficulty in swallowing. The disease is not completely understood till now but is thought to be triggered by any food allergy. About 15 to 55 cases of EoE per 100,000 peoples can be seen.

eosinophilic esophagitis pathogenesis

Figure 1. Mechanism of eosinophilic esophagitis pathogenesis (Photo credit: Ann Allergy Asthma Immunol. 2014 May;112(5):397-403. doi: 10.1016/j.anai.2014.01.023).

The Phase II clinical trial was performed on people of age group 11 to 40 years suffering from EoE. After 12 weeks, people receiving SHP621 BOS was compared with those on placebo, reduction in both dysphagia symptoms were seen. Higher number of patients showed histologic response. US FDA had already given Orphan Drug designation to BOS. Currently, SHP621 BOS is in Phase III trial for the evaluation of the efficacy of SHP621 BOS on EoE patients of age group 11 to 55 years. Currently, no treatment is available particularly for EoE. The Phase II trial data supported SHP621 BOS in achieving the Breakthrough status.

The other candidate, SHP625 is an oral, liquid formulation of maralixibat being developed for the treatment of several rare cholestatic liver diseases (PFIC) for pediatric patients. According to previous studies, maralixibat is a potent, selective inhibitor of the apical sodium-dependent bile acid transporter (ASBT). These inhibitors work by blocking the bile acid reabsorption in the ileum and by increasing the fecal bile acid secretion.

SHP625 maralixibat had received Orphan drug designation from FDA and EMA. It is currently being evaluated in a Phase II clinical trial for its efficiency in the treatment of PFIC. The interim results of Phase II clinical trial helped in the achievement of the Breakthrough designation which demonstrated significant reduction in the mean serum bile levels from baseline in the pediatric patients.

intrahepatic cholestasis mechanism

Figure 2. Interahepatic bile duct anatomy (Credit: Terese Winslow LLC/National Cancer Institute).

PFIC is a group of autosomal-recessive liver disorders occurring in children that disrupt bile formation and present with cholestasis. 10 to 15% of liver transplant occur in children due to PFIC and no specific treatment is available for PFIC till now. Among the three types of PFIC, PFIC2 is most common.

Receiving Breakthrough Therapy Designation on two pipeline products this past week reflects the potential of our strong and innovative pipeline of more than 60 programs,” said Flemming Ornskov, M.D., MPH, and CEO, Shire. “Shire is committed to bringing innovation to the rare and specialty areas we focus on. We persevere to see compounds through the many stages of development through their challenges and successes, and always keep patients with unmet needs top of mind”.

Featured Image: A Shire Plc logo sits on a wall outside the company’s offices at the Citywest Business Campus in Dublin, Ireland, on Wednesday, Oct. 15, 2014. (Photo credit: Aidan Crawley, Bloomberg)

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