One of Shire's top blockbuster drug prospects flops in a key PhII study

Shire CEO Flemming Ornskov

Two months ago Shire CEO Flemming Ornskov held up the rare liver disease drug SHP625 as a prime example of its most promising development programs. Today, though, Shire was forced to concede that the drug flopped against both the primary and secondary endpoints in the first of several Phase II studies.

Investigators for Shire had focused on serum bile acid levels and pruritis endpoints for 20 pediatric patients with Alagille syndrome, or ALGS. Shire noted that mean serum bile acid levels and pruritus had dropped by the end of the 13-week study for both the drug, formerly LUM001, as well as the placebo arm compared to baseline. Going back over the data, investigators drew a "positive correlation between percent changes from baseline in serum bile acid levels and pruritis" in the drug arm.

Shire acquired SHP625 in its $260 million-plus deal to buy San Diego-based Lumena 11 months ago. Like Lumena, the big biotech expected to hustle to regulators in an accelerated effort on rare cholestatic liver diseases. And combined with LUM002, Ornskov later pegged peak potential sales for the drugs at $3 billion as AbbVie was closing in on a buyout that was later scrapped.

Bernstein's Ronny Gal noted this morning that the news casts a shadow over the whole program, which includes two more midstage studies that read out later in the year. Gal has by no means abandoned the effort, but he also recognizes that the failure will make it harder for Shire to succeed in the near term.

"Whilst the smaller trial is tougher to accept, the lack of significant serum bile acid reduction from IMAGO makes the full SHP625 program less likely to succeed, and if it does succeed, it may now be less likely to deliver as strong results," Gal writes. "Based on conservative penetration rates (35% pediatric, 20% adult), sales potential for the product could be ~$2B. Today's news of course places some doubt into these estimates but for now we leave our £500M 2020 sales estimates unchanged."

Shire's stock ($SHPG) dipped 2% this morning.

"We have gained important insights from these first results from one of several phase 2 studies in the SHP625 development program," said Philip Vickers, Shire's R&D chief, in a statement. "We remain committed to continuing the ongoing studies of SHP625 in ALGS and other indications."

- here's the release

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