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Updated November 2022

An Overview of Gene Therapy for Hemophilia A/B

1. Pipeline Summary

The first gene therapy for Hemophilia B, Hemgenix™ (etranacogene dezaparvovec) was approved by the FDA in November 2022. Hemgenix was developed in partnership by uniQure with CSL Behring responsible for global commercialization, and debuted with a list price of $3.5M. 1

And a gene therapy Hemophilia A in the US is expected to be approved as early as March 2023, with BioMarin’s BLA submission for Roctavian™ (valoctocogene roxaparvovec) on Sep 29, 2022 2

If approved, Roctavian is expected to debut with a list price of $2-2.5M with an outcomes-based rebate measured on factor independence. This pricing structure was supported by an ICER’s report 3 , which found that Roctavian was cost-effective at $2-2.5M and saved approximately $4M over a lifetime versus Roche’s Hemlibra.

BioMarin also recently received conditional marketing authorization (CMA) for Roctavian in the EU in Aug 2022 4 , priced at approximately $1.5M. 5

Pfizer is also developing a gene therapy for Hemophilia B, PF-06838435, which is expecting a key Phase 3 readout in 2023.

2. How many patients would be eligible?

It is estimated there are around 20,000 people with Hemophilia A, 6 of which approximately 60% have the severe form of the disease. 7 After filtering for eligibility factors including adult patients, those with severe Hemophilia A who do not have any history of Factor VIII inhibitors or AAV5 antibodies, there could be up to 5,000 patients who are eligible for gene therapy.

Hemophilia B represents a smaller population, approximately 15% of all patients with Hemophilia.

3. What are the currently available treatments?

People living with Hemophilia A/B lack sufficient blood clotting Factor VIII and Factor IX respectively, resulting in painful and dangerous bleeding episodes that can have life-threatening complications and cause debilitating chronic joint damage. Those with severe hemophilia face a mortality rate that is 4-6x higher than the average.

Current treatments for A require regular infusions, and include-

  1. Recombinant Factor Concentrates that replace the missing blood clotting factor, and must be infused 2-3 times per week. (i.e Jivi for Factor VIII, BeneFIX for Factor IX)
  2. Antibodies that replace the function of Factor VIII/Factor IX and are infused 1-4 times per month (ie. Hemlibra for Factor VIII)

Even with consistent care, patients can still experience breakthrough bleed episodes, which can majorly impact quality of life.

4. ICER

ICER’s Final Evidence report published on Nov 2, 2022 outlined that they found a price of $3-4M for Hemophilia B and $2-2.5M for Hemophilia A to be a fair price based on simulations of cost savings and durability. ICER notes that these treatments are only cost-effective because they “[offset] the price of prophylaxis with existing agents that cost far in excess of $300,000 per year”, and that existing treatments “have prices that are not believed to be aligned with benefits to patients”. 8

ICER Cost-effective Price Range Listing Price
Etranacogene Dezaparvovec (Hemgenix, Hemophilia B) $3,000,000 - $4,000,000 depending on years of sustained benefit $3,500,000
Valoctocogene Roxaparvovec (Roctavian, Hemophilia A) $2,000,000 - $2,500,000 depending on years of sustained benefit Not yet approved

5. Listing Price & Outcomes-Based Contracting

Roctavian is likely to debut with a price of approximately $2.5M, higher than its EU price of $1.5M. This price was supported by ICER, which deemed Roctavian cost effective at up to $2.5M assuming a sustained benefit over 12 years. BioMarin has also stated that they plan to offer an outcomes-based warranty agreement that will measure factor independence over 4 years, ready to implement at launch. 9

References

[1] Commissioner, O. of the. (n.d.). FDA approves first gene therapy to treat adults with hemophilia B. U.S. Food and Drug Administration. Retrieved November 29, 2022, from https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b.
[2] BioMarin resubmits Biologics License Application (BLA) for Valoctocogene Roxaparvovec Aav gene therapy for severe hemophilia A to the FDA. BioMarin Investors. (n.d.). Retrieved November 29, 2022, from https://investors.biomarin.com/2022-09-29-BioMarin-Resubmits-Biologics-License-Application-BLA-for-Valoctocogene-Roxaparvovec-AAV-Gene-Therapy-for-Severe-Hemophilia-A-to-the-FDA
[3] ICER publishes evidence report on therapies for hemophilia A. ICER. (2022, July 11). Retrieved November 29, 2022, from https://icer.org/news-insights/press-releases/icer-publishes-evidence-report-on-therapies-for-hemophilia-a/
[4] First gene therapy for adults with severe hemophilia A, BioMarin's ROCTAVIAN™ (Valoctocogene Roxaparvovec), approved by European Commission (EC). BioMarin Investors. (n.d.). Retrieved November 29, 2022, from https://investors.biomarin.com/2022-08-24-First-Gene-Therapy-for-Adults-with-Severe-Hemophilia-A,-BioMarins-ROCTAVIAN-TM-valoctocogene-roxaparvovec-,-Approved-by-European-Commission-EC
[5] Bell, J. (2022, August 25). With European approval secured, BioMarin puts roughly $1.5m price tag on hemophilia gene therapy. BioPharma Dive. Retrieved November 29, 2022, from https://www.biopharmadive.com/news/with-european-approval-secured-biomarin-puts-roughly-15m-price-tag-on-he/630501/
[6] Centers for Disease Control and Prevention. (2022, August 8). A new study of hemophilia occurrence finds many more cases in the United States. Centers for Disease Control and Prevention. Retrieved November 29, 2022, from https://www.cdc.gov/ncbddd/hemophilia/features/keyfinding-hemophilia-occurrence-US.html
[7] What is hemophilia? Cleveland Clinic. (n.d.). Retrieved November 29, 2022, from https://my.clevelandclinic.org/health/diseases/14083-hemophilia .
[8] ICER publishes evidence report on therapies for hemophilia A. ICER. (2022, July 11). Retrieved November 29, 2022, from https://icer.org/news-insights/press-releases/icer-publishes-evidence-report-on-therapies-for-hemophilia-a/
[9] BioMarin's gene therapy for adults with severe hemophilia A, Roctavian™ (Valoctocogene Roxaparvovec), assessed to provide substantial cost savings per patient in a preliminary independent report. BioMarin Investors. (n.d.). Retrieved November 29, 2022, from https://investors.biomarin.com/2022-09-15-BioMarins-Gene-Therapy-for-Adults-with-Severe-Hemophilia-A,-ROCTAVIAN-TM-valoctocogene-roxaparvovec-,-Assessed-to-Provide-Substantial-Cost-Savings-Per-Patient-in-a-Preliminary-Independent-Report