Shire Steps Back in Hemophilia Gene Therapy Race, Scraps Baxalta Drug

Xconomy Boston — 

When Shire bought Baxalta earlier this year, one of the programs it inherited was a treatment that, at one point, was the leader in an emerging race to treat hemophilia with gene therapy. Competition has changed the landscape significantly, however, and now Shire has tossed that program onto the scrap heap.

On a conference call Tuesday, Shire (NASDAQ: SHPG) CEO Flemming Ornskov said that the Dublin and Lexington, MA, company has discontinued development of BAX 335, an experimental gene therapy for hemophilia B. The news was disclosed during Shire’s earnings call, in which the company went through the progress it has made integrating Baxalta following the $32 billion buyout that closed in June.

As part of any merger between two big drugmakers, some experimental drugs make it into the combined company’s portfolio, and some don’t. Ornksov put BAX 335 in the latter category, and added that while the company isn’t giving up on gene therapy in hemophilia, it’s focusing on a next-generation preclinical program for hemophilia B and an experimental hemophilia A treatment, BAX 888, that could begin trials either late this year or early next year.

Prior to the merger, Baxalta had indicated plans to move BAX 335 into Phase 3 trials, but Shire, according to a note from Leerink Partners analyst Michael Schmidt, is looking elsewhere because of the “inconsistent results” from the therapy so far. As Schmidt pointed out, in early-stage trials, BAX 335 has led to “inconsistent Factor IX activity levels and duration.” Hemophilia patients have damaged or absent genes for so-called clotting factors—like Factor IX in the case of hemophilia B—and rely on infusions of those proteins to stop dangerous bleeds. Gene therapy offers the potential for a long-lasting treatment, one which might, if all goes well, free patients from needing those infusions.

It’s been a multi-decade quest to bring a successful gene therapy to hemophilia, but over the past few years promising data in human patients has been produced by several companies, among them Spark Therapeutics (NASDAQ: ONCE), BioMarin Pharmaceutical (NASDAQ: BMRN), and UniQure (NASDAQ: QURE). It wasn’t too long ago, however, that Baxter International (NYSE: BAX) was the leader in this race because of BAX 335—the first of the new wave of hemophilia gene therapies to reach clinical trials.

BAX 335 originated from the work of Chatham Therapeutics, a Chapel Hill, NC, company that Baxter aligned with back in 2012 to begin exploring gene therapy programs for hemophilia A and B. Chatham was co-founded by gene therapy pioneer Jude Samulski, the director of the University of North Carolina’s gene therapy center, and Baxter invested in the company and later bought it out in 2014 (Samulski, meanwhile, just sold another gene therapy startup, Bamboo Therapeutics, to Pfizer earlier this week). That gave Baxter BAX 335—which began clinical testing in 2012—and a preclinical hemophilia A program. None of the other recent hemophilia gene therapy programs reached clinical trials until 2015.

In 2015, Baxter spun out its drugmaking work into a separate company, Baxalta, and the gene therapy programs went along with the new entity, which didn’t stay independent for long—Shire aggressively pursued Baxalta, and eventually agreed to buy it for $32 billion in January, a deal that closed in June.

In the meantime, Spark and UniQure caught up with BAX 335 and advanced early stage trials in hemophilia B, and BioMarin a began 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.

Still, the news of BAX 335’s demise opens the door further for Spark, UniQure, and others that are advancing hemophilia B treatments like Dimension Therapeutics (NASDAQ: DMTX) and Sangamo Biosciences (NASDAQ: SGMO). And as Schmidt noted, despite the fact that the hemophilia B gene therapy space is seen as “crowded” and Spark is in the lead, one company likely won’t dominate the space since certain patients have pre-existing antibodies that effectively neutralize specific gene therapies.

Here’s more on gene therapy, hemophilia, and the technical differences between those developing treatments.