May 26, 2024

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US$3.5 million per dose:  The worlds most expensive drug and Why?

US$3.5 million per dose:  The worlds most expensive drug and Why?


US$3.5 million per dose:  The worlds most expensive drug and Why?


In November last year and February this year, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) successively approved the launch of Hemgenix, the first gene therapy drug for hemophilia B[1,2], becoming the world ‘s most Records of expensive medicines.


US$3.5 million per dose:  The worlds most expensive drug and Why?

FDA screenshot

According to its announced pricing in the United States, Hemgenix costs US$3.5 million per dose.




How effective is the most expensive drug in the world?


Hemgenix, developed by UniQure and CSL Behring, is an AAV vector serotype 5 (AAV5)-based gene therapy for the treatment of hemophilia B.


Hemophilia B is a rare X-linked inherited bleeding disorder in which a deficiency of clotting factor IX (FIX) causes recurrent joint or soft tissue bleeding, leading to chronic pain, disability, and impaired quality of life. The global incidence of this disease is about 1/25000 (the domestic may be lower) .


At present, the clinical treatment of moderate and severe hemophilia is mainly through prophylactic infusion of recombinant FIX preparations or virus-inactivated blood-derived prothrombin complexes to replace the synthetic defects of coagulation factors[3 ] .

However, patients using these therapies must undergo rigorous life-long treatment, which is expensive. In addition, lifelong intravenous infusion of FIX concentrate may also lead to the production of neutralizing antibodies to FIX, making it less effective.


Hemgenix, on the other hand, uses gene therapy using the AAV vector, the least immunogenic of the viral serotypes.

The viral vector contains the FIX-Padua gene variant (Padua gene variant) under the control of a liver-specific promoter.

After intravenous administration and reaching the liver, the virus can stably exist in the liver cells and continuously express the FIX protein. Patients produce sufficient coagulation factor IX within a few weeks after treatment, and the activity remains at a high level [4] .


US$3.5 million per dose:  The worlds most expensive drug and Why?

Screenshot of research paper

According to a single-arm, single-dose phase III clinical trial published by the research and development company, the annual bleeding rate of 54 patients who received a single dose of Hemgenix decreased from 4.19 to 1.51, and the activity of coagulation factor IX was followed up 18 months after treatment.

Compared with the baseline, it increased by 34.3%. Ninety-four percent of participants discontinued all preventive replacement therapy within two years of treatment, and patients experienced significant improvements in health-related quality of life. No treatment-related serious adverse reactions were found in clinical trials [4] .



Plus, Hemgenix provides long-lasting protection. Another clinical trial data showed that a single dose of gene therapy can provide sufficient protection for patients with moderate to severe hemophilia for more than eight years [5] .


According to the drug instructions of Hemgenix, its indications are very broad, and all adult patients with hemophilia B who meet the following conditions have indications for medication and have no contraindications: including current use of factor IX prophylaxis, or current or past life-threatening bleeding, or recurrent severe spontaneous bleeding.


The birth of this drug has undoubtedly brought new hope to patients with hemophilia B.



US$3.5 million: is it a gospel for patients really?


However, while bringing hope, Hemgenix has also been involved in controversy because of its 24 million pricing.


For Hemgenix, gene therapy technology itself is also a relatively expensive technology. Studies have shown that the development of a new drug requires an average R&D cost of US$9.4 to US$2.83 billion [6] .

The number of patients with hemophilia B is small, and pharmaceutical companies developing such “orphan drugs” need to recover the huge R&D costs they have invested in a small patient population, which also affects drug pricing to a certain extent.


However, unlike CAR-T and other treatments, Hemgenix needs to modify the patient’s own cells for “private customization”. The same recombinant virus can be used for all patients, which also greatly reduces production costs.


So, how did the price of $3.5 million come from?


In fact, CSL Behering did not justify the pricing through calculations of production costs and upstream research costs, but instead made an economic assessment based on the lifetime cost of preventive treatments.


According to the data of the American Hemophilia Foundation, for patients with severe hemophilia B, if they want to obtain a relatively good quality of life and avoid accidents such as bleeding, the average annual cost of coagulation factor replacement therapy alone will exceed 300,000 US dollars .

Another data shows that in the United States, the lifetime cost of treatment for patients with moderate to severe hemophilia B exceeds 20 million US dollars.


After treatment with Hemgenix’s gene therapy, patients can achieve long-term remission after medication, greatly reducing future medical care costs.

Even at the exorbitant $3.5 million price tag, Hemgenix could save the U.S. healthcare system between $5 million and $5.8 million per treated person by reducing or eliminating the need for patients to receive regular injections of clotting factor IX, according to CSL Behring. [1] .


Still , Hemgenix’s high price has raised concerns among many experts and organizations.


“For middle-income countries, these savings numbers may not work for them if the health benefits of these treatments are immediate, but the potential savings occur in the future,” said Dr. Rena Conti said.


In addition, many organizations are also trying to provide more sustainable solutions for gene therapy drugs for patients in low-income countries, such as transferring technology and knowledge to local manufacturers, or collaborating with local governments and organizations to promote and support healthcare plan.


In addition to Hemgenix, there are many other AAV vector-based gene therapies currently in development.

For example, BioMarin is developing an AAV5 vector-based gene therapy for the treatment of hemophilia A, which has completed phase III clinical trials; Sangamo Therapeutics and Pfizer are also collaborating to develop a hemophilia based on gene editing technology. Hemophilia treatment drugs, by directly editing the patient’s gene to treat hemophilia.


It is foreseeable that more gene therapies will continue to emerge in the future, and the record of the most expensive drug in the world is likely to be continuously refreshed. So, who will pay for this huge sum of money?


For expensive gene therapy, there is no mature pricing and insurance reimbursement solution.

Taking the United States as an example, drug prices are mainly set based on what the market can bear; in European countries, price negotiations are regulated by the national health system, so prices are generally lower than those in the United States.


In addition, gene therapy makers typically employ a reimbursement model called Value-Based Agreements.

It allows manufacturers to negotiate the price of a drug with payers in order to receive higher compensation when the drug works as expected. For example, a manufacturer might agree to offer a discount or refund if a drug fails to work as expected, providing payers with more assurance.


CSL Behring is also working on “truly” innovative payment models to support local reimbursement, adapted to national health insurance systems, with a view to “reflecting the clinical, economic and social value of treatment” while “helping manage budgetary impacts and ensuring that healthcare systems sustainability”. 







1. Nature News Researchers welcome $3.5-million haemophilia gene therapy — but questions remain (
2. Bloomberg News World’s Most Expensive Drug Revives Push for New Payment Models (
3. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. N Engl J Med. 2023 Feb 23;388(8):706-718. doi: 10.1056/NEJMoa2211644. PMID: 36812434.
4. Adeno-Associated Mediated Gene Transfer for Hemophilia B:8 Year Follow up and Impact of Removing “Empty Viral Particles” on Safety and Efficacy of Gene Transfer. Blood, 2018. Doi: 10.1182/blood-2018-99-118334.
5. R&D Costs of New Medicines: A Landscape Analysis. Frontiers in Medicine. 2021. Doi: 10.3389/fmed.2021.760762

US$3.5 million per dose:  The worlds most expensive drug and Why?

(source:internet, reference only)

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Important Note: The information provided is for informational purposes only and should not be considered as medical advice.