First Patient Treated in Phase 3 Trial of AMT-061 in Hemophilia B

A Phase 3 clinical trial of treatment candidate AMT-061 for severe and moderately severe hemophilia B has treated its first patient.

The open-label HOPE-B study (NCT03569891) is testing the safety and effectiveness of AMT-061 in adult men with hemophilia B. Patient recruitment is continuing for an estimated total of 56 participants at sites in the U.S. and U.K. More information on contacts and locations can be found here.

“We are very pleased to have successfully administered AMT-061 to the first patient enrolled in the HOPE-B pivotal trial and mark this as a milestone for the field in advancing a potential one-time treatment for patients with hemophilia B,” Robert Gut, MD, PhD, uniQure’s chief medical officer, said in a press release.

Gut also said he was “extremely proud” of uniQure’s work to advance the trial and that patient enrollment is expected to be completed before the end of the year.

Hemophilia B is caused by mutations in the gene that provides instructions for making factor IX (FIX), leading to the absence or impaired function of this clotting protein. uniQure’s AMT-061 uses a specific viral vector — adenovirus type 5 (AAV5) — containing a gene that generates a mutated form of FIX, also known as the Padua variant (FIX-Padua), to increase production of FIX.

HOPE-B includes a six-month phase to collect initial information, with participants serving as their own controls while on standard treatment, followed by administration of a single intravenous (into-the-vein) dose of AMT-061.

The primary outcome is to assess FIX activity at 26 weeks of treatment. Secondary measures include annualized bleeding rate and use of FIX replacement therapy, as well as assessments of adverse events. The patients will be followed for five years after treatment.

uniQure is also conducting a dose-confirmation Phase 2b trial (NCT03489291) of AMT-061 in three adults who also have severe or moderately severe hemophilia B. Recent results revealed that, six weeks after treatment, mean FIX activity for the three patients was 31% of the norm, while FIX levels kept increasing beyond the initial six to 10 weeks of follow-up. No patient required FIX replacement therapy, reported bleeding events, or needed immunosuppressive therapy.

“Our mission in hemophilia B has always been to be first to market with a best-in-class gene therapy,” said Matt Kapusta, the company’s CEO.

He added that the start of the dosing phase of HOPE-B and the findings from the Phase 2b trial lead uniQure to believe it is on track toward its goal of “developing the first gene therapy that provides durable, functionally-curative benefits to nearly all patients with hemophilia B,” without inducing viral capsid-related immune responses or patients requiring immunosuppressants.

According to uniQure, AAV5-based gene therapies have shown good safety and tolerability results in multiple clinical trials, including four of the company’s own studies in hemophilia B and other indications. In addition, preclinical and clinical data suggested that these therapies may be effective in patients with pre-existing antibodies to AAV5, which could increase patient eligibility compared with other gene therapy candidates.

In 2017, AMT-061 was granted breakthrough therapy designation by the U.S. Food and Drug Administration, based on results from a Phase 1/2 trial (NCT02396342) of its sister gene therapy, AMT-060, shown to be safe and effective for up to two years. These two treatments only differ in a small variation in the gene sequence for FIX. AMT-061 was also granted priority status, known as a PRIME designation — by the European Medicines Agency.