Etranacogene dezaparvovec for the treatment of adult patients with severe and moderately severe hemophilia B

ABSTRACT

Introduction

Etranacogene dezaparvovec is the first gene therapy approved for treatment of adults with severe and moderately severe hemophilia B.

Areas covered

This review describes the results of the clinical trial program of AMT-060 and etranacogene dezaparvovec, outlining the pharmacokinetic, clinical efficacy and safety data. With the entry of etranacogene dezaparvovec into the market, this review summarizes the treatment landscape in hemophilia B and discusses the current unknowns in the field.

Expert opinion

Gene therapy appears to be a feasible option for adults with severe and moderately severe hemophilia B. Etranacogene dezaparvovec enables most patients to reach stable factor IX (FIX) levels after a single intravenous infusion, eliminating the need for regular prophylaxis; thus, drastically reducing treatment burden and avoiding variable bleeding risk owing to fluctuating FIX activity levels. Efficacy of etranacogene dezaparvovec has been demonstrated even in the presence of preexisting neutralizing antibodies (up to a titer of 1:678), with a relative low risk of transaminitis and its associated potential loss of transgene expression. However, long-term data are required to ascertain the durability of FIX levels achieved and safety. The cost-effectiveness and adoption of innovative payment models for reimbursement are key in choosing gene therapy over existing treatments.

KEYWORDS:

• Adeno-associated viral vector
• etranacogene dezaparvovec
• factor IX
• gene therapy
• hemophilia B

Article highlights

• Gene therapy has the potential to change the lives of individual patients but will also have broader implications on how the field of hemophilia is organized.

• Etranacogene dezaparvovec is the first gene therapy approved for treatment of adult patients with severe and moderately severe hemophilia B.

• Overall, etranacogene dezaparvovec provides stable FIX expression up to 2 years post-infusion (mean FIX level of 36%).

• Etranacogene dezaparvovec reduced annualized bleeding rates by 64% up to 2 years post-infusion and the majority of patients were able to discontinue prophylaxis with FIX replacement products.

• Efficacy was also maintained in the presence of preexisting antibodies against adeno-associated virus type 5 (up to a titer of 1:678).

• Etranacogene dezaparvovec demonstrated a favorable safety profile and was well tolerated up to 2 years post-administration.

Declaration of interests

G Castaman has received honoraria as a speaker/participant on advisory boards for Alexion, Bayer, BioMarin, Shire/Takeda, CSL Behring, Novo Nordisk, Sobi, Roche, uniQure, Sanofi, Werfen, Kedrion, LFB, and Grifols.

M Coppens has received financial support for research from Anthos, Bayer, CSL Behring, NovoNordisk, and Roche, and honoraria for lecturing or consultancy from Alexion, Bayer, CSL Behring, Daiichi Sankyo, Octapharma, Pfizer, Sobi, and Viatris. Non-financial conflicts of interest: member of the gene therapy working group of the European Association for Haemophilia and Allied Disorders (EAHAD), member of the European Reference Network (ERN) EuroBloodNet.

SW Pipe has received consulting fees from Apcintex, ASC Therapeutics, Bayer, BioMarin, CSL Behring, Equilibra Bioscience, GenVentiv, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron/Intellia, Roche/Genentech, Sanofi, Takeda, Spark Therapeutics, and uniQure.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript is an advisory board member for CSL Behring and BioMarin. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Scientific accuracy review

CSL Behring provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

Medical writing support for this paper was funded by CSL Behring.