UniQure Shares Long-term Data About AMT-061 and AMT-060 Gene Therapy Candidates

Two potential gene therapies — AMT-060 and AMT-061 (etranacogene dezaparvovec) — lead to safe and long-term increases in factor IX (FIX) activity, as well as fewer bleeds among patients with hemophilia B, according to the therapies’ maker, uniQure.

The company announced in a press release that it presented two-year follow-up data for AMT-061 and five-year results for AMT-060 at the virtual 62nd  Annual Meeting of the American Society of Hematology.

The two gene therapies deliver functional versions of the F9 gene, which is mutated in people with hemophilia B, via a harmless viral vector known as AAV5. AMT-061, designed to be an improved version of AMT-060, carries an engineered FIX variant called the Padua variant (FIX-Padua), which boosts FIX activity approximately eightfold to ninefold.

Three patients with severe hemophilia B — FIX activity no more than 1% — received a single infusion of 2×10¹³ genome copies/kg of AMT-061 in a Phase 2b trial (NCT03489291).

In an oral presentation, titled “Etranacogene dezaparvovec (AAV5-Padua hFIX variant), an Enhanced Vector for Gene Transfer in Adults with Severe or Moderate-Severe Hemophilia B: Two Year Data from a Phase 2b Trial,” the company showed that all three show sustained FIX activity at therapeutic levels two years after their single infusion.

The mean FIX activity for the three was 44.2% of normal, up from 41% at one year post-infusion. Individually, one patient showed FIX activity 44.7% of normal, another measured 51.6% of normal, and the third patient achieved FIX activity of 36.3% of normal.

Two of the three patients have remained bleed-free and have not needed to use FIX replacement therapy. One participant has reported a single bleed and used two FIX infusions, excluding surgery. None have needed preventive therapy in the two years since receiving AMT-061.

In the first year of follow-up, one patient had reported a transient headache and slightly elevated C-reactive protein levels (a measure of inflammation) that were related to treatment. No adverse events (side effects) associated with AMT-061 were reported in the second year.

The three individuals will continue to be monitored for a total of five years. None has developed FIX inhibitors (neutralizing antibodies).

“The data offer encouraging support for the potential long-term benefits of etranacogene dezaparvovec, which are being further characterized in the ongoing Phase 3 HOPE-B study,” said Annette von Drygalski, MD, director of the Hemophilia and Thrombosis Treatment Center at the University of California San Diego and a principal investigator in the trial.

Ricardo Dolmetsch, president of research and development at uniQure, added: “These data will be included in regulatory submissions to the FDA [U.S. Food and Drug Administration] and EMA [European Medicines Agency], which we anticipate will begin in the second half of 2021, along with FIX activity and bleeding rates from the ongoing HOPE-B Phase III pivotal trial.”

UniQure also presented results of its ongoing Phase 1/2 study (NCT02396342) of AMT-060 in a poster titled “AMT-060 Gene Therapy in Adults with Severe or Moderate-Severe Hemophilia B Confirm Stable FIX Expression and Durable Reductions in Bleeding and Factor IX Consumption for up to 5 Years.”

In line with a previous update, all 10 patients enrolled in this study continue to show sustained increases in FIX activity, reduced need for FIX replacement therapy, and fewer bleeds at 4.5 years post-treatment. No treatment-related side effects or inhibitor development have been reported in the year since the last assessment.

Participants in this trial were assigned to two AMT-060 dosage groups of five patients each. One received 5×10¹² gc/kg and the other received a higher dose of 2×10¹³ gc/kg, the same being used in HOPE-B.

From the six months of data collected in this fifth year, the mean annualized bleeding rate — ABR, the estimated number of bleeds per year — of patients on the higher dose was zero, which compared to four in the year prior to treatment. Usage of FIX replacement therapy also declined to zero from 173,200 international units (IU) before treatment.

By year five, individuals in the lower dose group showed a mean ABR of 6.5, down from 14.4, and used an average of 57,913 IU of FIX replacement therapy, down from 354,800 IU (an 84% decrease).

Mean FIX activity was 7.4% over 4.5 years since treatment in the higher dose group, and 5.2% over five years in those receiving the lower dose.

“In up to 5 years after a single administration, the Phase I/II study of AMT-060 has now demonstrated clear evidence of long-term clinical benefits in these patients, including sustained increases in FIX activity, improved disease phenotype [status] and substantial reductions in bleeding,” said Frank W.G. Leebeek, MD, PhD, of the Erasmus University Medical Center in Rotterdam.

UniQure plans to incorporate data from this trial in its regulatory submissions for marketing approval of AMT-061.