Pfizer's $3.5 Million Gene Therapy Durveqtix: A One-Shot Cure Redefining Hemophilia B Treatment

Aug 26, 2024 14:24 CST Updated 14:24

Pfizer

Pharmaceutical R&D Developer

Author of this article: Tina

Last month, Pfizer's hemophilia gene therapy Durveqtix received conditional approval from the European Commission, and prior to this, the drug had already been approved for marketing by the FDA in April this year.

Screenshot of the EMA website

For patients with hemophilia B, this one-time gene therapy is undoubtedly highly attractive — with just a single treatment, the vast majority of patients can return to a normal life.

But along with the anticipation,质疑声也络绎不绝，原因很简单——价格太高了。

A dose that could buy a riverside property in Shanghai, but how effective is it?

According to public information from Pfizer, the expected price per dose of Durveqtix is $3.5 million (approximately RMB 24.93 million), matching the previously approvedAnother Gene Therapy Drug for Hemophilia B: Hemgenix。

Currently, among the "Top Ten Most Expensive Drugs Globally" that have been disclosed worldwide[3], Durveqtix ranks second alongside Hemgenix, second only to the price of 4.25 million US dollars (approximately 30.28 million yuan)The World's Most Expensive Drug: Lenmeldy。

Previously, the world's most expensive drug Lenmeldy was approved - official website announcement

Why is Durveqtix so expensive? This has to do with the mechanism of this drug.

Durveqtix is a gene therapy made using an adeno-associated virus (AAV) vector.It introduces a plasmid containing the full-length coagulation factor IX into the adeno-associated virus Rh74 variant. Once these modified AAVs enter the body, they quickly "infect" liver cells responsible for secreting coagulation factors, thereby increasing the synthesis of coagulation factor IX in the body and correcting the deficiency of coagulation factor IX in patients with hemophilia B.[1]。

In the Phase III clinical trial of this drug, a total of 102 patients received treatment.[2]Among them, 59 patients completed a 6-month follow-up. After a single treatment and months of recovery, the average annual number of bleeding events per patient decreased by 71% compared to when using clotting factor replacement therapy, and the use of clotting factor treatment also significantly reduced; in the clinical trial, 64% of patients never experienced a bleeding event after treatment.

In terms of safety, only 6 patients developed anti-plasmid antibodies after receiving Durveqtix treatment and resumed coagulation factor therapy. However, after receiving corticosteroid treatment, most patients have discontinued coagulation factor therapy again, and Durveqtix treatment remains effective.

Gene Therapy: Why Does It Repeatedly Break the Record for "The World's Most Expensive"?

In fact, the price controversy triggered by Durveqtix has also appeared in many previously approved cell and gene therapies.In the currently published list of "The World's Top Ten Most Expensive Drugs," cell and gene therapies occupy the top five spots.

Why Does the Field of Gene Therapy Keep Producing "Million-Dollar Babies"?

First,Among existing commercialized therapies, gene therapy ranks among the highest in research and development costs.Gene therapy involves several steps, including constructing vectors in vitro, evaluating vector efficacy through animal trials, assessing vector efficacy and safety in Phase I clinical studies, and fully evaluating therapeutic efficacy in Phase II/III studies. The high costs of various research and development tools further increase the trial-and-error costs for companies.

Taking Zolgensma, ranked sixth on the list and one of the currently best-selling gene therapies, as an example, the price per dose is $2.1 million (approximately RMB 14.95 million). However, according to disclosures from Novartis, the pharmaceutical company that developed the drug, the total investment in Zolgensma's research and development reached $9.4 billion (approximately RMB 66.9 billion).[5], and generally speaking, the research and development cost of chemical drugs is mostly hundreds of millions of US dollars.

Image source: Tuchong Creatives

Such high investment is not uncommon in the field of gene therapy.A 2023 paper estimated the research and development costs of cell therapy and gene therapy.[6]It was found that the average cost of a cell therapy/gene therapy drug in the clinical trial stage is $1.943 billion (approximately RMB 13.8 billion), while the applicable population may only be a few hundred or even dozens of patients.

Therefore,R&D companies often set higher prices for gene therapies to amortize profits and R&D costs.

Secondly, gene therapy is mostly a "one-time treatment," and the vast majority of patients experience significant symptom improvement or even complete recovery after treatment.Although the price of a single gene therapy is expensive, from a long-term perspective, the cost of gene therapy may be cheaper than lifelong use of traditional therapies.

Taking Durveqtix as an example[4]Although the price is as high as 3.5 million US dollars, the annual cost for hemophilia B patients in the United States to receive clotting factor treatment can be up to 1.1 million US dollars. If gene therapy can free patients from clotting factor treatment, then this cost can "break even" after three years of treatment.

Amidst Applause and Controversy, Some Drugs Have Quietly Withdrawn from the Market

With prices set, how well are these therapies, which cost millions of dollars, selling?

In fact, the vast majority of revenue from gene therapy comes not from patients, but from insurance.

For example, in some countries, the cost of gene therapy for patients who meet the indications can be partially or fully reimbursed by health insurance, and pharmaceutical companies also carry out drug donation programs globally through charitable organizations. In addition, some pharmaceutical companies have reached agreements with insurance companies for installment payments or pay-for-performance.InPay by EffectivenessUnder the agreement, the insurance company can gradually pay the cost based on the treatment efficacy, and if the treatment fails, the pharmaceutical company will refund part or all of the treatment costs.

In terms of sales results, Zolgensma, a gene therapy ranked seventh in the "Top Ten Most Expensive Drugs Worldwide," is a relatively ideal case.

Despite its extremely high research and development costs and premium pricing, Zolgensma has chosen a relatively common track among rare diseases – Spinal Muscular Atrophy (SMA).

At the same time, this drug demonstrated quite impressive efficacy during the clinical trial phase: at 24 months after treatment, 100% of patients were able to survive without tracheal intubation, and 75% of patients could sit unassisted for at least 30 seconds—these outcomes are almost impossible to achieve in untreated patients.[8]

With various accolades, Zolgensma's sales reached $160 million in the first quarter after its launch, and its sales in 2021 amounted to $1.351 billion.Sales further increased to $1.37 billion in 2022, even surpassing the oral drug risdiplam ($1.173 billion in sales for 2022), which is also used to treat spinal muscular atrophy.

Zolgensma has received clinical trial implied permission from the Center for Drug Evaluation of the National Medical Products Administration.

But not every gene therapy is so "lucky."

As shown in the "Top Ten Most Expensive Drugs Globally," Skysona and Zynteglo, ranked fifth and sixth respectively, reported sales of $16.7 million (approximately RMB 119 million) and $12.4 million (approximately RMB 88.28 million) in 2023, according to the company's annual report.[10]。

Currently, these two therapies have also been withdrawn from the European market one after another due to "corporate strategy issues."

Another example is Elevidys, a gene therapy product ranked fourth for the treatment of Duchenne muscular dystrophy, which attracted attention from Nature after receiving FDA accelerated approval.[11]The questioning of efficacy by major medical media.

Most reports believe that Elevidys has mild efficacy and very few suitable patients, making it difficult to be profitable. However, the persistence of the research and development company eventually demonstrated the potential of Elevidys — based on the results of two clinical studies, Elevidys received FDA approval for a significant expansion of its indications.[12], expanding from the original limitation to children aged 4-5 years with walking ability, to children aged 4 years and above (regardless of their walking ability).

Currently,Elevidys sales reached $200 million (approximately RMB 1.42 billion) in 2023, which can also be considered a "hot sale" among gene therapy products.

Compiled from Reference 3

As of now, following the approval of Durveqtix, the top seven spots on the "World's Top 10 Most Expensive Drugs" list have been entirely taken by cell and gene therapies. On this track filled with both opportunities and challenges, the next update to the rankings may come sooner than expected.

Planner: z_popeye | Producer: carollero

Source of the title image: Tuchong Creative

References:

[1]https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-beqveztm-fidanacogene-elaparvovec

[2]https://genetherapy.isth.org/efficacy-and-safety-of-fidanacogene-elaparvovec-in-adults-with-moderately-severe-or-severe-hemophilia-b-results-from-the-phase-3-benegene-2-gene-therapy-trial

[3]https://www.drugs.com/article/top-10-most-expensive-drugs.html

[4]https://www.fiercepharma.com/pharma/pfizer-scores-fda-nod-hemophilia-b-gene-therapy-will-charge-35m-dose

[5]https://www.spglobal.com/marketintelligence/en/news-insights/latest-news-headlines/r-d-report-card-zolgensma-maker-novartis-spending-reaches-9-4b-in-2019-60760144

[6]Sabatini MT, Chalmers M. The Cost of Biotech Innovation: Exploring Research and Development Costs of Cell and Gene Therapies. Pharmaceut Med. 2023;37(5):365-375. doi: 10.1007/s40290-023-00480-0

[7] Schlander M, Hernandez-Villafuerte K, Cheng CY, et al. How Much Does It Cost to Research and Develop a New Drug? A Systematic Review and Assessment. Pharmacoeconomics. 2021;39(11):1243-1269. doi: 10.1007/s40273-021-01065-y

[8] https://www.zolgensma-hcp.com/clinical-experiences/start-trial-efficacy/

[9]https://www.biopharmadive.com/news/novartis-zolgensma-sales-slow-newborn-screening/634896/

[10]https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-fourth-quarter-and-2023-annual-results-and

[11]Mullard A. FDA approves first gene therapy for Duchenne muscular dystrophy, despite internal objections. Nat Rev Drug Discov. 2023 Jun 23. doi: 10.1038/d41573-023-00103-y

[12]https://www.fda.gov/news-events/press-announcements/fda-expands-approval-gene-therapy-patients-duchenne-muscular-dystrophy

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