Shire hemophilia A candidate SHP656, or PSA-recombinant Factor VIII (rFVIII), which uses a platform developed by Xenetic Biosciences, failed to show efficacy for once-weekly dosing in a Phase I/II clinical study, Xenetic acknowledged today.

“While Shire is disappointed by this outcome, the company is encouraged by the knowledge gained through this research and remains committed to transforming the treatment landscape for patients with bleeding disorders,” Philip Vickers, Ph.D., Shire’s global head of R&D, said in a statement.

Shire inherited SHP656 (formerly BAX826) when the company and Baxalta completed their $32 billion merger last year, creating a combined company focused on hematology and other therapeutic areas.

SHP656 is being developed as a long-acting therapeutic for hemophilia A that uses Xenetic's PolyXen™ platform technology to conjugate polysialic acid to therapeutic blood-clotting factors. The platform is designed to create proprietary next-generation protein therapeutics by attaching polysialic acid to existing protein or peptide therapeutics. The attachment increases the therapeutics’ size, which reduces systemic clearance rates, while shielding the protein from other degradation pathways, with the aim of improving their pharmacological properties.

In developing SHP656, Shire and Xenetic have sought to introduce a FVIII protein that can significantly prolong the circulating half-life of the FVIII protein in order to provide a once-weekly or less frequent dose, thus creating the longest-acting hemophilia A factor replacement treatment.

The Phase I/II study showed efficacy and pharmacokinetic data for SHP656 that were commensurate with the profile of an extended half-life rFVIII product, and the candidate generated no drug-related adverse events, serious adverse events, or rFVIII inhibitors, Xenetic added.

“Given the potential application of polysialic acid technology, the companies will explore future collaborations,” Dr. Vickers added.

In earlier clinical and preclinical studies, Xenetic said, therapeutic proteins polysialylated with the PolyXen™ platform had been shown to have extended circulating half-life, improved thermodynamic stability, and resistance to proteases, while retaining pharmacological activity.

“Moving forward, we believe data from Shire’s SHP656 program continues to support the broad utility of our proprietary PolyXen technology platform, and we remain focused on building a growing pipeline of partnerships utilizing this proven platform,” Xenetic CEO M. Scott Maguire stated. “We truly value our continuing relationship with Shire and look forward to exploring other potential applications of PolyXen within the Shire portfolio.”

In January, Xenetic received a $3 million milestone payment from Shire related to advancing the Phase I/II clinical study.

Baxalta licensed the candidate from Xenetic in 2014, agreeing to pay up to $100 million tied to achieving development, regulatory, sales, and deadline extension milestones, plus royalties on potential net sales. At the time, Shire made a $10 million equity investment in Xenetic. Combined with an earlier $3 million equity investment, Shire is one of Xenetic’s largest shareholders.

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