Shire Kills Baxalta's Hemophilia B Program; Clears Path for BioMarin, Spark Therapeutics and uniQure

August 3, 2016
By Mark Terry, BioSpace.com Breaking News Staff

When companies merge, there’s almost always fallout—sometimes it’s jobs and sometimes it’s programs. When Shire acquired Bannockburn, Ill.-based Baxalta earlier this year, a certain number of job cuts were expected, and on May 1, Baxalta laid off 239 people. Now, during yesterday’s quarterly finances conference call, Shire indicated it was killing what had seemed to be a very promising hemophilia B program, BAX 335.

Although Shire isn’t abandoning hemophilia and gene therapy, it has decided instead to focus on a next-generation preclinical program for hemophilia B. It also will direct attention to its hemophilia A drug, BAX 888, that the company expects will start trials by the end of this year or early in 2017.

Before the merger closed, Baxalta planned to push BAX 335 into Phase III clinical trials. Michael Schmidt, an analyst with Leerink Partners, said in a note to investors, “Shire’s announced on their 2Q16 earnings call today that they are discontinuing development of clinical stage hemophilia B gene therapy program BAX-335 and are focusing on advancing a different preclinical program instead given the inconsistent results seen to date.”

Data on the Phase I/II clinical trial of BAX 335 was released in the first half of 2015, and showed limited promise. It is a gene therapy technique that used an AAV8 (adeno-associated virus serotype 8) to deliver factor IX (FIX) Padua, which resulted in the FIX levels of one of the trial’s participates to increase by 20 to 25 percent for a year. That one patient, however, was not enough to ensure the program’s success.

“The expression was good but it was a little inconsistent between different patients,” said Philip Vickers, head of Shire’s research-and-development, during the conference call. “And, with time for some patients, the level of expression decreased.”

Vickers and Shire believe they understand the technical problems related to the inconsistency and can apply that to a next-generation program.

Hemophilia gene therapy is a fairly competitive area these days, with several companies focused on developing a breakout product. Those companies include Spark Therapeutics , BioMarin Pharmaceutical , and UniQure .

Baxalta’s BAX 335 was picked up from Chatham Therapeutics in 2012. Chatham was co-founded by the director of the University of North Carolina’s gene therapy center, Jude Samulski. Baxter , which spun out Baxalta last July, invested in Chatham in 2012 and bought it in 2014. Samulski, just this week, sold a different gene therapy company, Bamboo Therapeutics, to Pfizer .

Xconomy writes, “In the meantime, Spark and UniQure caught up with BAX 335 and advanced early stage trials in hemophilia B, and BioMarin began a human study of a hemophilia A treatment that, so far, has produced promising results. Spark and BioMarin, which both presented their latest results at the World Hemophilia Federation World Congress last week, are now seen as the leaders in each respective category—though of course it’s still early and much more data has to be accrued to really understand who will respond to each treatment, and for how long.”

In his note to investors, Schmidt noted that Shire dropping the program was “incrementally positive for UniQure, since competition in hemophilia B has formed a major overhang on the stock. While several other gene therapy programs are currently in clinical development, and Spark Therapeutics’ has generated highly impressive clinical data to date, we believe that it is unlikely that one single gene therapy product will be used to treat all hemophilia B due to the product-specific limitations (e.g. neutralizing antibodies).”