Shire cans Baxalta hemophilia B gene therapy, thinning field for uniQure, Spark

Shire ($SHPG) has scrapped plans to further develop BAX 335, a hemophilia B gene therapy it gained in its $32 billion takeover of Baxalta. The move will see Shire focus its attention on a preclinical gene therapy program it thinks has a better chance of success, clearing the path for uniQure ($QURE) and Spark Therapeutics ($ONCE) to beat their bigger rival to market.

Baxalta had advanced the gene therapy as far as a Phase I/II clinical trial, early data from which were released more than one year ago. Those results showed the gene therapy, which uses an AAV8 vector to deliver factor IX (FIX) Padua, elevated the FIX activity of one participant by 20% to 25% for a full year. Yet, while this represented a success for this one patient over that period of time, the overall, longer-term dataset has failed to convince Shire that BAX 335 is worth pursuing.

“The expression was good but it was a little inconsistent between different patients. And, with time for some patients, the level of expression decreased,” Philip Vickers, head of R&D at Shire, said on a conference call with investors to discuss the company’s second-quarter results.

Shire plans to use the experience gained in the clinic to shape a preclinical program. Vickers said the team has an idea of some of the technical factors that could account for the inconsistency and slide in activity over time. And, with the Phase I/II trial showing that when the AAV8 vector works, it works well, Shire thinks it has the makings of an effective asset. Baxalta, through its then parent company Baxter ($BAX), acquired the AAV8 vector in the $70 million takeover of Chatham Therapeutics.

The decision to scrap BAX 335 removes one of the more advanced riders from the congested race to bring a hemophilia B gene therapy to market. As recently as last month, Baxalta was revising the list of clinical trial sites in the Phase I/II study and BAX 335 was still penciled in to start Phase III this year. Now, Shire has pulled the plug on the trial, shortening the odds that one of the biotechs leading the pack will bring a hemophilia B gene therapy to market before their bigger rival.

UniQure and Spark have both delivered some clinical data on their gene therapies, while Dimension Therapeutics ($DMTX) and Sangamo Biosciences ($SGMO) are closing in on that point, too. Of the group, uniQure is seen by investors as having the most to gain from the scrapping of BAX 335. The share price of the Dutch biotech, which has taken repeated hits over the past year, rose 8.5% on the day Shire revealed its decision. Dimension, Sangamo and Spark all closed down.

While both BAX 335 and Spark’s SPK-FIX use FIX Padua, uniQure’s program is built on AAV5 and wild-type FIX. So far, the approach pursued by Baxalta and Spark has delivered bigger increases in FIX activity. However, uniQure has yet to post data from a cohort of patients who have received a higher dose of its gene therapy. And its use of AAV5 positions it to treat the approximately 40% of patients who are ineligible for AAV8 or AAV8-derived capsids because they have neutralizing antibodies. Whether FIX Padua or the wild type is more effective long-term is unclear.

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