Efanesoctocog alfa


Efanesoctocog alfa is the first once-weekly factor VIII (FVIII) replacement intravenous infusion therapy, which will help reduce the burden associated with the injection frequency of other currently available FVIII therapies. For patients reluctant to receive novel therapies, such as mAbs or gene therapy, efanesoctocog alfa will likely be an appealing option. Clinicians also view efanesoctocog alfa favorably given the attainable FVIIII levels, injection frequency and safety profile demonstrated in clinical trials to date.

Sanofi has development and commercialization rights for efanesoctocog alfa in the United States, whereas Swedish Orphan Biovitrum (Sobi) is responsible for developing and marketing the drug in Europe and other markets.

efanesoctocog alfa

  1. Sanofi (Bioverativ Therapeutics Inc) and Swedish Orphan Biovitrum AB
  2. Recombinant FVIII replacement therapy
  3. Once weekly intravenous infusion for routine prophylaxis to prevent bleeding, on-demand treatment for control of bleeding episodes, and perioperative management of bleeding in adults and children with hemophilia A
  4. ~45K diagnosed prevalent cases of hemophilia A in the G7 markets in 2023

Why is it a drug to watch?

To potentially extend its time in circulation, efanesoctocog alfa adds a region of von Willebrand factor and XTEN® polypeptides to the innovative Fc fusion technology. It is the only therapy that has been shown to break through the von Willebrand factor ceiling, which is believed to impose a half-life limitation on current FVIII therapies. The result is the first FVIII replacement therapy that is administered only once a week, reducing the treatment burden.

The U.S. FDA approval was primarily based on data from the pivotal phase 3 XTEND-1 study conducted over a period of 52 weeks with adult and adolescent (>12 years) patients with severe hemophilia A who had been previously treated with either a FVIII prophylaxis treatment or FVIII on-demand therapy. Patients who were on FVIII prophylaxis pre-study received efanesoctocog alfa for routine prophylaxis (arm A). Patients who received on-demand treatment with FVIII pre-study were assigned to receive on-demand efanesoctocog alfa treatment for 26 weeks, followed by routine prophylaxis once weekly for 26 weeks (arm B). The study results for once weekly efanesoctocog alfa prophylaxis included the following:

  1. Median annualized bleeding rates (ABRs) of 0, 21.1 and 0 in arm A, B (on-demand) and B (prophylaxis), respectively
  2. Mean ABRs of 0.7, 21.4 and 0.7 in arms A, B (on-demand) and B (prophylaxis), respectively
  3. In arm A, a 77% reduction in ABR, based on an intra-patient comparison with prior factor prophylaxis
  4. >40 IU/dL mean FVIII activity for the majority of the week, with 15 IU/dL at day 7
  5. For all participants with target joints at baseline, resolution of all target joints after 12 months of prophylactic treatment with efanesoctocog alfa
  6. Improved patient-reported physical health and pain intensity
  7. No signs of FVIII inhibitor development in the study :

The phase 3 XTEND-Kids study was also conducted over 52 weeks with previously treated children (<12 years) with severe hemophilia A and found the following for once weekly efanesoctocog alfa prophylaxis:

  1. Median and mean ABR of 0 and 0.89, respectively
  2. No signs of FVIII inhibitor development

Ongoing studies include the following:

  1. XTEND-ed: extension study to evaluate the long-term efficacy and safety
  2. FREEDOM: phase 3b European trial with patients with severe hemophilia A aged 12 years and older who are currently on prophylactic therapy
  3. Prospective, observational, longitudinal cohort study to describe the real-world effectiveness, safety and treatment use of efanesoctocog alfa in patients with hemophilia A treated per standard of care in the United States and Japan

Review and
approval status

August 2017

  • Orphan Drug designation granted: U.S. FDA

June 2019

  • Orphan Drug designation granted: EMA

February 2021

  • Fast Track designation granted: U.S. FDA

July 2021

  • Breakthrough therapy designation granted: Mainland China

June 2022

  • Breakthrough therapy designation granted: U.S. FDA

February 2023
For adult and pediatric patients with hemophilia A

  • Approved: U.S. FDA

May 2023

  • Marketing authorization application (MAA) accepted: EMA

September 2023
For adult and pediatric patients with hemophilia A

  • Approved: Japan MHLW

Actual and expected launch:

  • 2023: Japan, United States
  • 2024: European Union
  • 2028: Mainland China

Patents estimated to expire beginning in 2032

How will efanesoctocog alfa impact the market for hemophilia A?

  1. The hemophilia A treatment landscape is becoming increasingly crowded.
  2. Despite the development of treatment burden-reducing therapies with subcutaneous administration, a sizable percentage of patients who do well on FVIII replacement therapy will likely continue with the treatment. These patients may have good venous access, become accustomed to lifelong IV infusions or very few bleeds.
  3. Even with alternative treatment options, some breakthrough bleeds are inevitable. These, as well as postsurgical management and trauma-related bleeds, will continue to require treatment with FVIII.
  4. The hemophilia A patient population is aging because the expected median survival time of hemophilia patients in the G7 countries is approaching background life expectancy. In addition to an increased number of treatable patients and longer overall treatment duration, the older hemophilia A patient population will undergo more major surgeries during which they may require hemostatic interventions, such as continuous FVIII infusions.
  5. Because factor replacement therapies are dosed based on patient weight, proportionate increases in weight per age will drive the increase in per-unit consumption of drugs, ultimately contributing to sales growth.

What gaps in treatment does efanesoctocog alfa fill?

A primary goal in the treatment of hemophilia A is to prevent bleeding, particularly bleeding into the joints, which is associated with permanent joint damage. Another important outcome is better quality of life. However, the dosing frequency and route of administration for current FVIII replacement therapies are burdensome and contribute to suboptimal compliance rates. As the first once-weekly FVIII replacement infusion therapy, efanesoctocog alfa could improve patient convenience, reduce the treatment burden and enhance treatment compliance.

What hurdles might it need to overcome to reach blockbuster status?

Treating hemophilia is expensive, especially for patients with severe bleeding tendencies, and both clinicians and payers are asking for precise quantification of the value of a treatment regimen. As a lower-cost subcutaneously administered treatment option that is currently available for patients, HEMLIBRA® (Genentech) continues to constrain the value of the market with its increasing adoption. Although also likely to be costly initially, emerging gene therapies could be curative and reduce the need for invasive standard treatments, such as FVIII replacement therapy.

expected sales in 2029
probability of success for efanesoctocog alfa in the European Union
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

Drug Timeline &
Success Rates

– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

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