European Medicines Company Commences Evaluation of Novel Gene Remedy Candidate Etranacogene Dezaparvovec for Individuals with Hemophilia B

Advertising and marketing Authorization Software (MAA) for etranacogene dezaparvovec might be reviewed beneath accelerated evaluation and has the potential to be the primary gene remedy for sufferers dwelling with hemophilia B

MAA submitting is supported by the section 3 HOPE-B examine which demonstrated sturdy and sustained therapeutic impact after a single infusion

Milestone underscores CSL Behring’s promise to develop and ship a very distinctive portfolio of patient-focused therapies

MARBURG, Germany, March 28, 2022 /PRNewswire/ — World biotherapeutics chief CSL Behring at this time introduced that the European Medicines Company (EMA) has accepted the Advertising and marketing Authorization Software (MAA) for etranacogene dezaparvovec (EtranaDez) beneath its accelerated evaluation process. Etranacogene dezaparvovec is an investigational adeno-associated virus 5 (AAV5)-based gene remedy administered as a one-time therapy for hemophilia B sufferers with a extreme bleeding phenotype. If accredited, etranacogene dezaparvovec will present folks dwelling with hemophilia B within the European Union (EU) and European Financial Space (EEA) with the first-ever gene remedy therapy choice that considerably reduces the speed of annual bleeds after a single infusion. Accelerated evaluation probably reduces the timeline as soon as the MAA is accepted for assessment and is offered for a medicinal product when the remedy is anticipated to be of main public well being curiosity, significantly pertaining to therapeutic innovation.

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“As the primary gene remedy candidate for hemophilia B, this pivotal regulatory milestone brings CSL Behring one step nearer to delivering on the promise of gene remedy for the bleeding problems neighborhood,” mentioned Emmanuelle Lecomte Brisset, Head of World Regulatory Affairs at CSL Behring. “We sit up for working with regulatory authorities to carry the transformative potential of gene remedy to folks dwelling with this debilitating, life-long situation.”

The MAA is supported by constructive findings from the pivotal HOPE-B trial, the biggest gene remedy trial in hemophilia B to this point. Hemophilia B sufferers categorised as having a extreme bleeding phenotype handled with etranacogene dezaparvovec demonstrated lowered adjusted annualized bleed price (ABR) by 64% and demonstrated superiority to prophylaxis therapy at 18 months post-treatment in comparison with a 6-month run in interval. Moreover, there was steady and sturdy will increase in imply Issue IX (FIX) exercise ranges. Etranacogene dezaparvovec was particularly designed to make near-normal blood-clotting capacity doable by addressing the underlying reason for the situation: a defective F9 gene that causes a deficiency in clotting Issue IX (FIX).

“The acceptance of etranacogene dezaparvovec for assessment by the EMA furthers our relentless pursuit to enhance the lives and well-being of these dwelling with hemophilia B and different uncommon and critical medical problems,” mentioned Invoice Mezzanotte, Govt Vice President, Head of R&D and Chief Medical Officer for CSL Restricted. “We’re proud to work with uniQure to be on the forefront of this scientific development which goals to make hemophilia B a secondary a part of a affected person’s life as an alternative of a continuing concern.”

The multi-year scientific growth was led by uniQure (Nasdaq: QURE) and sponsorship of the scientific trials in america has transitioned to CSL Behring after its buying world rights to commercialize etranacogene dezaparvovec. CSL Behring is within the strategy of transitioning sponsorship of the scientific trials within the European Union.

About Hemophilia B
Hemophilia B is a life-threatening degenerative illness. Individuals with the situation are significantly weak to bleeds of their joints, muscular tissues, and inner organs, resulting in ache, swelling, and joint harm. Present therapy contains life-long prophylactic infusions of FIX to briefly substitute or complement low ranges of the blood-clotting issue.

About Gene Remedy in Hemophilia B
Gene remedy has the potential to make a useful treatment doable in hemophilia B. Gene remedy achieves this with modified non-infectious viruses known as “vectors” that may enter sure cells. Vectors carry genetic directions to particular cells. As soon as delivered, the brand new genetic directions permit the mobile equipment to provide their very own steady ranges of FIX. A sure kind of vector, known as an adeno-associated virus, or AAV, dissolves after delivering its genetic directions. These genetic directions stay within the goal cells, however by no means truly turn into part of an individual’s personal DNA.

About Etranacogene Dezaparvovec
Etranacogene dezaparvovec (also called CSL222, beforehand generally known as AMT-061) makes use of a selected kind of AAV, known as AAV5, as its vector. The AAV5 vector carries the Padua gene variant of Issue IX (FIX-Padua), which generates FIX proteins which can be 5x-8x extra lively than regular. Preclinical and scientific knowledge present that AAV5-based gene therapies could also be clinically efficient in as much as 95 % of hemophilia B sufferers with pre-existing antibodies to AAV vectors, thereby probably growing affected person eligibility for therapy in comparison with different AAV gene remedy product candidates.

Concerning the Pivotal HOPE-B Trial
The pivotal Section III HOPE-B trial is a multinational, open-label, single-arm examine to judge the protection and efficacy of etranacogene dezaparvovec. Fifty-four grownup hemophilia B sufferers categorised as having a extreme bleeding phenotype and requiring prophylactic FIX alternative remedy had been enrolled in a potential, six-month observational interval throughout which period they continued to make use of their present normal of care remedy to determine a baseline Annual Bleeding Charge (ABR). After the six-month lead-in interval, sufferers obtained a single intravenous administration of etranacogene dezaparvovec on the 2×10^13 gc/kg dose. Sufferers weren’t excluded from the trial based mostly on pre-existing neutralizing antibodies (NAbs) to AAV5. A complete of 54 sufferers obtained a single dose of etranacogene dezaparvovec within the pivotal trial, with 53 sufferers finishing a minimum of 18 months of follow-up. The first endpoint within the pivotal HOPE-B examine was 52-week ABR after achievement of steady FIX expression in contrast with the six-month lead-in interval. For this endpoint, ABR was measured from month seven to month 18 after infusion, guaranteeing the remark interval represented a steady-state FIX transgene expression. Secondary endpoints included evaluation of FIX exercise and statistical superiority of ABR after dosing.

Outcomes from the pivotal HOPE-B examine demonstrated that etranacogene dezaparvovec produced imply FIX exercise of 39.0 IU/dL at six months and 36.9 IU/dL at 18 months publish infusion. After the six-month lead-in interval post-infusion, the adjusted annualized bleeding price (ABR) (1.51) for all bleeds was lowered by 64 % (p=0.0002) and all FIX-treated bleeds was lowered by 77 % (3.65 to 0.83; p<0.0001) over months seven to 18. As well as, 98 % of topics handled with a full dose of etranacogene dezaparvovec discontinued use of prophylaxis, with an total 97 % discount in imply unadjusted annualized FIX consumption of 257338.8 IU/yr/participant to 8486.6 IU/yr/participant (from lead-in interval to months 13-18).

Etranacogene dezaparvovec is usually well-tolerated with nearly all of hostile occasions (80.4 %) thought of delicate. One demise ensuing from urosepsis and cardiogenic shock in a 77-year-old affected person at 65 weeks following dosing was thought of unrelated to therapy by investigators and the corporate sponsor. A critical hostile occasion of hepatocellular carcinoma was decided to be unrelated to therapy with etranacogene dezaparvovec by unbiased molecular tumor characterization and vector integration evaluation. No inhibitors to FIX had been reported.

About CSL Behring
CSL Behring is a worldwide biotherapeutics chief pushed by our promise to avoid wasting lives. Centered on serving sufferers’ wants by utilizing the most recent applied sciences, we uncover, develop and ship modern therapies for folks dwelling with circumstances within the immunology, hematology, cardiovascular and metabolic, respiratory, and transplant therapeutic areas. We use three strategic scientific platforms of plasma fractionation, recombinant protein expertise, and cell and gene remedy to help continued innovation and regularly refine methods through which merchandise can tackle unmet medical wants and assist sufferers lead full lives.

CSL Behring operates one of many world’s largest plasma assortment networks, CSL Plasma. The mum or dad firm, CSL Limited (ASX:CSL;USOTC:CSLLY), headquartered in Melbourne, Australia, employs greater than 25,000 folks worldwide, and delivers its life-saving therapies to folks in additional than 100 international locations. For uplifting tales in regards to the promise of biotechnology, go to Vita and observe us on

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