FDA ‘breakthrough’ tags for Shire’s rare GI drugs

Shire CEO
(Shire CEO)

Shire ($SHPG) has been given a breakthrough designation from the FDA for its two experimental gastrointestinal meds SHP621 and SHP625, which should speed up the regulatory review process.

The Irish Big Biotech said today it was given the BTD for its two rare disease candidates: SHP621 (budesonide oral suspension, or BOS) for eosinophilic esophagitis (EoE), and SHP625 (maralixibat) for progressive familial intrahepatic cholestasis type 2 (PFIC2).

EoE is a chronic and rare disease that stems from an elevated number of eosinophils--a type of white blood cell that infiltrates the walls of the esophagus and can lead to patients having difficulty swallowing.

PFIC refers to a group of autosomal-recessive liver disorders of childhood that disrupt bile formation. Symptoms include severe itching of the skin and jaundice, although it is rare, affecting just 1 in 50,000 to 1 in 100,000 births.

SHP621 is essentially a new formulation of AstraZeneca’s ($AZN) aging lung drug and steroid Pulmicort (budesonide) that works as a topically active, oral viscous formulation of the treatment--a treatment it gained from its $70 million-plus deal to buy out Meritage Pharma last year. AstraZeneca has also sold the steroid as an inflammatory bowel disease therapy, known as Entocort.

In a recent open-label clinical trial, Shire’s version, which coats the esophagus, was more effective than nebulized or swallowed budesonide for improving esophageal eosinophil counts and endoscopic findings in adults with a new diagnosis of EoE.

The BTD was granted based on the results from a Phase II trial in patients (ages 11-40) with EoE. The co-primary endpoints were met and, compared with placebo, 12 weeks of budesonide oral suspension treatment significantly reduced both swallowing difficulties and achieved higher proportion of subjects with histologic response. BOS already has orphan drug designation from the FDA and is currently in Phase III testing.

SHP625 meanwhile is in mid-stage testing for PFIC2. SHP625 was brought into Shire’s portfolio under the $260 million-plus purchase of Lumena Pharmaceuticals back in 2014, but both the deal and the drug have suffered in the intervening years.

In April, buried within its Q1 results, Shire released a mixed bag of data from its Phase II Cameo non-comparative open-label trial for SHP625--a 14-week study in patients with primary sclerosing cholangitis (PSC).

Although achieving “significant reductions” from baseline in serum bile acids and pruritus by ItchRO score, there was no significant reduction from baseline in serum alkaline phosphatase or other liver parameters, meaning it missed its secondary endpoints.

And that came exactly a year after Shire posted data from SHP625 (formerly known as LUM001) that showed it missed all of its objectives in the Phase II Imago study involving 20 children with the genetic disease Alagille syndrome.

Shire told FierceBiotech in April that it “continues to analyze the totality of the SHP625 data to determine an appropriate path forward.”

Its new BTD for PFIC2 hope has also come with some troublesome data. The FDA’s coveted tag was based on a Phase II single-arm, open-label study INDIGO in pediatric patients with PFIC.

The interim results of Indigo were however poor, showing no statistically significant reduction in mean serum bile levels from baseline across the study population as a whole.

But Shire has drilled down into the data and found a subpopulation of patients with PFIC2 that showed decreases from baseline in serum bile acids, marked reductions in pruritus (skin itching), and normalization of liver parameters in those patients with liver enzymes that were elevated at baseline. More details were not posted.

There were however also some fairly big AEs, with 12 of the 33 patients enrolled (36.4%) having a “serious treatment-emergent adverse event,” of whom 4 patients (12.1%) experienced a total of 5 serious treatment-emergent adverse events--which an investigator confirmed came because of their treatment with Shire’s drug.

But Shire, which recently completed its $32 billion takeover of Baxalta, was happy with the news. "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, CEO at 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."

- check out Shire’s release

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