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For Key Study, UniQure Allowed to Swap Hemophilia Gene Therapies

Xconomy Boston — 

UniQure is trying to get to the finish line for a hemophilia B gene therapy by switching horses mid-race—and it says it has the blessing from regulators to make the unusual change.

The company had been testing a gene therapy candidate called AMT-060 in early-stage clinical trials, with good data to show for it. But uniQure, which has its operations in Amsterdam, the Netherlands, and Lexington, MA, now says a different therapy, AMT-061, should better prevent the bleeding experienced by hemophilia B patients. It will push into Phase 3 studies with AMT-061.

UniQure’s (NASDAQ: QURE) stock price soared by more than 50 percent to $14.25 per share following the announcement Thursday.

Hemophilia B patients have a genetic mutation that leads to defective or missing factor IX (FIX), a clotting protein. Without it, patients are more susceptible to bleeding, both internally and externally. UniQure says AMT-060 and AMT-061 are identical, except that AMT-061 substitutes two nucleotides in the coding sequence. The company says this change increases the activity of FIX, including the levels of the protein circulating in the blood and the clotting that the protein is meant to do.

In a conference call, chief scientific officer Sander van Deventer said a study of AMT-061 in non-human primates showed FIX activity 6.5 times higher than AMT-060. Furthermore, the study revealed no significant toxicity findings. Van Deventer said uniQure will present the study at the American Society of Hematology conference in December.

The safety and efficacy groundwork laid by AMT-060, already tested in 10 patients in a Phase 1/2 study, will carry over to AMT-061. Both U.S. and European regulators will allow the new drug to carry on under rules that speed up the review of medicines for unmet needs.

The new plans mark a turnaround for uniQure, which began a corporate restructuring nearly a year ago. Though in 2012 it became the first company to win regulatory approval for a gene therapy, Glybera, the rare-disease treatment was a commercial flop. In April, uniQure pulled the therapy from Europe, the only market where it was approved. The corporate restructuring refocused uniQure on hemophilia B and other programs.

In hemophilia B, uniQure is in a race against Spark Therapeutics (NASDAQ: ONCE), whose gene therapy candidate in early clinical studies has the backing of drug giant Pfizer (NYSE: PFE). Philadelphia-based Spark is currently awaiting an FDA decision on a different gene therapy, a treatment for inherited retinal disorders that lead to blindness.

Steve Zelenkofske, uniQure’s chief medical officer, said a pivotal Phase 3 study of AMT-061 could begin enrolling patients in the third quarter of next year. The study will be an open label, single-dose trial that will evaluate the safety and efficacy of the therapy in 30-50 patient patients who have severe or moderately severe hemophilia B. The main goal would be to show that the therapy is not inferior to the standard of care in preventing bleeding. Patients will be their own control, observed for six months to establish a baseline before being transferred to the uniQure therapy. Before that trial begins, uniQure will run a short study in three patients to lock in the right dose.

In a separate but related announcement, uniQure said that it has acquired the patents that cover the genetic variant for FIX used in AMT-061 and its use in gene therapy to treat bleeding disorders.

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