Single Dose of Gene Therapy AMT-061 Proves Effective in Hemophilia B

A single administration of AMT-061, an investigational gene therapy for people with severe and moderately severe hemophilia B, increased therapeutic levels of factor IX (FIX) in all patients enrolled in uniQure’s ongoing Phase 2b trial, the company announced.

Ultimately, this trial’s purpose is to confirm the dose of AMT-061 for the pivotal Phase 3 HOPE-B study (NCT03569891) focused on the safety and efficacy of uniQure’s gene therapy in severe and moderately severe hemophilia B. The trial is still recruiting patients.

Preliminary data were presented at the 12th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) in Prague, Czech Republic.

AMT-061 uses a viral vector (AAV5) to deliver the gene for a mutated clotting factor IX (FIX) called the Padua variant (FIX-Padua). This man-made mutation leads to approximately an eight- to nine-fold increase in FIX activity, compromised in hemophilia B patients.

In 2017, AMT-061 was named Breakthrough Therapy and Priority Medicine (PRIME) by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), respectively.

In this open-label, single-dose, single-arm, multicenter, Phase 2b trial (NCT03489291), three participants with severe or moderately severe hemophilia B (FIX activity levels below 1%) received a single dose of AMT-061 and will be monitored for one year to evaluate FIX activity, bleeding rates and usage of FIX replacement therapy.

AMT-061’s safety, including adverse events, will also be assessed for a five-year period post AMT-061 single administration.

The first patient was dosed approximately six months ago. At 12 weeks, mean FIX activity levels for the three patients increased to 38% of normal, which is more than enough to eliminate or decrease patients’ bleeding risk.

Sixteen weeks post AMT-061 administration, the first patient had almost half the FIX activity levels (48%) found in a healthy subject.

The second participant had 25 percent of normal FIX activity at 14 weeks, while the third patient showed more than half (51 percent) of normal FIX activity at 12 weeks after AMT-061 infusion.

Two of these patients had previously been denied enrollment in another adeno-associated virus (AAV)-mediated gene therapy trial because they had antibodies against the therapy’s vector, blocking its therapeutic activity.

“We are extremely pleased with these updated data,” Robert Gut, MD, PhD, chief medical officer of uniQure, said in a news release. “The study demonstrates AMT-061 has the potential to increase FIX activity into the normal range and continues to be very well-tolerated, with no serious adverse events reported and no patients requiring any immunosuppression therapy. We look forward to providing further updates on these patients later in the year at other academic conferences.”

So far, none of the patients had FIX activity levels reduced, and none experienced bleeding episodes or required replacement FIX infusions.

Only one patient experienced slight elevations of a liver enzyme called alanine aminotransferase, or ALT, which could indicate liver damage, but protein levels were normalized without additional medical intervention or loss of FIX activity.

“Our goal with AMT-061 is to give all people living with hemophilia B access to a one-time treatment capable of normalizing FIX activity and eliminating the need for replacement therapy, without the risk of immune responses that require immunosuppression or may lead to a loss of efficacy,” said Matt Kapusta, MBA, chief executive officer of uniQure.

“These updated data continue to suggest that AMT-061 may be the first gene therapy able to achieve this goal, and we remain focused on completing enrollment in our ongoing pivotal Phase 3 study by the end of the year,” he said.