uniQure Gene Therapy AMT-060 Shows Long-term Efficacy in Hemophilia B Patients

Gene therapy company uniQure released new data showing that its lead therapy AMT-060 for severe and moderately severe hemophilia B is safe and effective for up to two years, with adults requiring fewer doses of replacement therapy and showing a marked decrease in the spontaneous bleeding rate.

The results support uniQure’s clinical program and a new global program for its investigational gene therapy AMT-061 in patients with moderate to severe hemophilia B, set for 2018.

Top-line results from the first patients treated with AMT-061 are expected to be released before the end of the year.

Gene therapies are showing promise for diseases caused by genetic mutations. The principle behind this strategy is to replace the faulty gene with a healthy one.

AMT-061 is composed of an AAV5 viral vector that contains the gene for the mutated factor IX (FIX), called Padua variant (FIX-Padua). FIX is an important clotting protein that is deficient in people with hemophilia B.

Last year, the U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation to AMT-061 based on results from the ongoing Phase 1/2 study of its sister gene therapy, AMT-060. AMT-061 and AMT-060 are identical therapies except for a small variation in the gene sequence for FIX.

Similarly, the European Medicines Agency (EMA) also granted PRIME designation to AMT-061 in 2017. Like the FDA’s breakthrough therapy status, PRIME accelerates the development of medicines that target an unmet medical need.

These decisions were supported by data from the ongoing Phase 1/2 study (NCT02396342) of AMT-060 in patients with severe hemophilia B, recently published in the journal Blood.

In the study, “Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B,” researchers report the results of a one-year follow-up of patients enrolled in the trial’s low-dose cohort and of a six-month follow-up of those in the higher-dose cohort.

The results showed that a single infusion of AMT-060 was well-tolerated and resulted in a stable and clinically relevant increase in FIX activity. The therapy also led to a 53% decrease in patients’ mean annualized spontaneous bleeding rate (ASBR), and the need for additional FIX use was reduced by 81%. In the higher-dose cohort, annualized FIX use decreased by 73%, and mean ASBR was reduced by 70% – from 3.0 to 0.9.

Additional follow-up of these patients was presented at the 59th American Society of Hematology (ASH) Annual Meeting, in a presentation titled “Stable Elevations in FIX Activity and Reductions in Annualized Bleeding Rate over up to 2 Years of Follow-up of Adults with Severe or Moderate-Severe Hemophilia B Treated with AMT-060 (AAV5-hFIX) Gene Therapy.”

Researchers showed that AMT-060 was safe and well-tolerated and continued to lead to clinically meaningful elevations in FIX protein expression and activity after two years and 1.5 years of follow-up in the low-dose and higher-dose cohort, respectively.

“The data from the Phase I/II trial show that our AAV5-based gene therapies offer multi-year durability and a favorable immunogenicity profile, enabling hemophilia B patients to discontinue frequent infusions of FIX replacement therapy and to reduce the risk of spontaneous bleeding,” Dr. Steven Zelenkofske, chief medical officer of uniQure, said in a press release.

“With AAV5 emerging as a potential best-in-class vector for systemic administration to the liver, we look forward to advancing AAV5-FIX-Padua (AMT-061) into a pivotal trial in 2018,” he added.

uniQure and the FDA established a protocol that is nearly complete and confirms the similar activity between AMT-060 and AMT-061. The company is filing for an amendment to its existing Investigational New Drug (IND) application.