Successful results were announced by uniQure for its gene therapy, AMT-061, on hemophilia B patients

The United States FDA granted Breakthrough Therapy Designation to AMT-061.

The European Medicines Agency gave it access to the Priority Medicine (PRIME) regulatory initiative.

Gene therapy firm, uniQure (QURE), announced updated clinical data in patients treated in the ongoing Phase 2b study of AMT-061; an investigational AAV5-based gene therapy containing a patent-protected  FIX9-Padua (Factor 9) for the treatment of patients with severe and moderately severe hemophilia B. The announced data, which were presented in an oral session at the Annual Congress of the European Association for Hemophilia and Allied Disorders (EAHAD), demonstrated that therapeutic levels of Factor IX (FIX) activity continue to be sustained in all three patients up to sixteen weeks after a single administration of AMT-061.  

The Phase 2b Study of AMT-061

An open-label, single-dose, single-arm, multi-center trial being conducted in the United States. Three patients with severe hemophilia (endogenous FIX activity less than one percent) were enrolled in the study and received a single intravenous infusion of 2×10 vc/kg. Prior to the administration of AMT-061 all three patients showed low levels of pre-existing antibodies to AAV5 but were not excluded from the trial on that basis.

The AMT-061 Data

Updated data presented at EAHAD demonstrate that all three patients FIX levels have increased and sustained their levels since the one-time administration of AMT-061.

At twelve weeks, the mean FIX activity for the three patients increased to 38% of normal, which  exceeded threshold FIX levels generally considered sufficient to eliminate or significantly reduce the risk of bleeding events.

The first patient achieved FIX activity of 48% of normal at sixteen weeks after administration.

The second patient achieved FIX activity was 25% of normal at fourteen weeks after administration.

The third patient achieved FIX activity of 51% of normal at twelve weeks after administration.

The second and third patients had previously screen-failed and were excluded from another gene therapy study due to pre-existing neutralizing antibodies to a different AAV vector.

The Pivotal, Phase III HOPE-B trial

A multinational, multi-center, open-label, single-arm study to evaluate the safety and efficacy of AMT-061. Approximately 50 adult hemophilia B patients classified as severe or moderately severe will be enrolled in a six-month observational period during which time they will continue to use their current standard of care to establish a baseline control. After the six-month lead-in period, patients will receive a single intravenous administration of AMT-061. Dosing of patients in the HOPE-B pivotal trial is now underway.

The primary endpoint of the study will be based on the FIX activity level achieved following the administration of AMT-061; the secondary endpoints will measure annualized FIX replacement therapy usage, annualized bleed rates and safety.

A Word from uniQure

Explaining his enthusiasm for the results, Robert Gut, M.D., Ph.D. Chief Medical Officer of uniQure ,said that 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 required any immunosuppression therapy.  According to the results, no patient in the study has experienced a material loss of FIX activity, reported any bleeding events or required any infusions of FIX replacement therapy. As previously reported, one patient experienced slight elevations in the liver enzyme aspartate aminotransferase (AST), which quickly resolved without any additional treatment or loss of FIX activity. No patient has experienced any material elevation in alanine aminotransferase (ALT) after the administration of AMT-061.

Matt Kapusta, Chief Executive Officer of uniQure, stated that the updated data continue to suggest that AMT-061 may be the first gene therapy able to achieve this goal and that the firm will  continue focusing on completing enrollment in the ongoing pivotal Phase 3 study by the end of the year.

Patients in the Phase IIb study will be followed for 52 weeks to assess FIX activity, bleeding rates and usage of FIX replacement therapy, and will be monitored for five years to evaluate the safety of AMT-061. 

Investor Conference Call and Webcast Information

A conference call has already been hosted by uniQure on February 8, 2019. The Company discussed the updated clinical data from the Phase 2b study of AMT-061. For those who did not listen to the webcast a replay of the call will be available for two weeks on the Company’s website at 

AMT-061 consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). Multiple issued patents are currently held by uniQure in the United States and Canada broadly covering methods of treating bleeding disorders, including hemophilia B,using AAV gene therapy with the FIX-Padua variant. Additional patents are pending in the European Union.

Prohost Observations

The emergence of the advanced adeno-associated vectors, by some companies, led the FDA to insinuate that gene therapy is expected to reach the clinic. It did, as a matter of fact. We have already seen Spark Therapeutics (ONCE) advance Luxturna to the clinic; the gene therapy for inherited retinal disease caused by mutations in both copies of the RPE65 gene and who have enough remaining cells in the retina.

We are also expecting the approval of the gene therapy AVXS-101 for spinal muscular dystrophy. The product was developed by the biotech company, AveXis that was acquired by Novartis (NVS).

We remind that AveXis had licensed the adeno-associated vector used in AVXS-101 from RegenxBio (RGNX).      

The vector used for uniQure gene therapy product AMT-061 is AAA5, which is patented by the firm.  The AAA5 vector has demonstrated safety and tolerability in four of clinical trials. According to the firm no patient treated in clinical trials with the AAV5 gene therapies experienced any cytotoxic T-cell-mediated immune response to the capsid. Additionally, as you read above, preclinical and clinical data show that AAV5-based gene therapies may be clinically effective even in patients with pre-existing antibodies to AAV5. Thereby potentially increasing patient eligibility for treatment compared to other gene therapy product candidates. 

We have great tendency to add uniQure to the Prohost Portfolio. However, we are still debating this decision.

Be sure to read our upcoming article about uniQure, which we will post under Today’s Highlights.

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