The High Cost of Hope: Gene Therapy for Rare Diseases


Von Maxim Sharakin

In recent years, a transformative shift has occurred in the landscape of therapy approval for rare diseases, with regulatory bodies increasingly favoring the entry of novel treatments to be fast in reaching patients in need. This departure from the conventional gold standard trial, where one group of patients receives the treatment and the other doesn’t, toward reliance on evidence from trials where all patients receive the treatment and have smaller sample sizes prompts critical questions about patient safety, the genuine efficacy of therapies, and the issue of determining fair pricing.

This paradigm shift raises important considerations:

  • Why has there been a relaxation in policy for evidence generation?
  • Are patients now more vulnerable to potential side effects while paying for therapies with uncertain benefits?
  • How should these innovative therapies, particularly gene therapies, be priced to balance affordability and sustainability?

As we delve into the intriguing case of gene therapy for Duchenne Muscular Dystrophy (DMD), we explore the delicate balance between the urgent need to bring potentially life-changing therapies to patients and the imperative to ensure robust evidence of their efficacy and reasonable pricing. The complexities inherent in this discussion underscore the evolving nature of health economics in the face of groundbreaking medical advancements.

Discriminating data

Over 7% of Switzerland’s population, more than half a million individuals, grapple with rare diseases, often life-threatening and lacking a cure. DMD is a prime example, a genetic condition leading to progressive muscle loss, severe mobility issues, and premature death. In the United States (US), the gene therapy Delandistrogene Moxeparvovec (DM) gained approval for DMD based on evidence from three clinical trials, focusing on motor function. A high quality trial initially showed no significant improvement, but a subgroup analysis and a comparison against an external group suggested a potential positive moderate efficacy of the intervention. An analysis of the data derived from all the trials showed an acceptable safety profile.

Would you pay USD 3.2 million for DM?

The recent market debut of DM in the US comes with a substantial price tag of USD 3.2 million, prompting an in-depth exploration into the justification of this cost. A parallel cost-effectiveness analysis, conducted within the same national setting, contemplates the intervention’s potential cost-effectiveness up to an upper limit of USD 5.1 million. According to the analysis, the high price is justified based on the assumption that the treatment will remain effective for at least 10 years. However, this assumption is supported only by a 4-year trial involving a sample size of four patients.

Navigating the Nuances

While a casual glance might prompt skepticism about justifying the reimbursement of the intervention at its seemingly high price, diving deeper reveals nuances that significantly shape this decision-making process.

As a result of the life-threatening nature of the disease, it is no longer conceivable to recruit a group of patients that will not receive a potentially life-saving therapy in a clinical trial. Thus, regulators are forced to accept trials where treated patients cannot be compared against untreated patients. Additionally, due to the rarity of the disease, it is now deemed acceptable for clinical trials to involve a smaller number of patients. However, a lack of a comparator group and lack of large enough sample sizes also makes it more difficult to prove that the treatment is effective. 

In the context of DMD, these aspects might be responsible for the mixed evidence on the clinical benefits of the treatment. A solution that has been introduced is the comparison of outcomes between those patients that have been recruited by the trial against those that have not participated and therefore haven’t received the gene therapy. In this case, the results showed a clinically relevant benefit of DM.

Additionally, apart from the four-year trial, there is a biologic reason to believe that the treatment benefits will be maintained in the long-term. DM targets muscle cells specifically and has been shown to increase the number of healthy cells over a period of one year. Muscle cells are the ones responsible for DMD and they are known to have a very long lifespan.

Cost-Effectiveness in Context: Unraveling the Complete Picture

Whereas some evidence suggests in favor of a clinically relevant benefit associated with the treatment with DM, the evidence is not very strong and the price of the treatment high.

Only time can show if DM is as effective as seems. However, patients cannot be deprived of a potentially lifesaving and only treatment option. As a result, it is not uncommon for payers to accept the high prices under the condition that gene therapy manufacturers continue monitoring the efficacy of the treatments for longer periods of time.

What if the treatment turns out to be less effective than expected in the long-term after the payment has already been made? There is some evidence that a booster injection would not be possible since after the first injection antibodies against DM form. It is now becoming more common for the payer to agree on alternative payment schemes such as dividing the payment across several years until new evidence becomes available.

Maxim Sharakin is Scientific Associate in Health Technology Assessment (HTA) and Health-Economic Assessments.


Website  Numerous rare diseases and many people affected (
Website First Gene Therapy for Duchenne Priced at $3.2 Million (
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Alexa C. Klimchak, Lauren E. Sedita, Louise R. Rodino-Klapac, Jerry R. Mendell, Craig M. McDonald, Katherine L. Gooch & Daniel C. Malone (2023) Assessing the value of delandistrogene moxeparvovec (SRP-9001) gene therapy in patients with Duchenne muscular dystrophy in the United States, Journal of Market Access & Health Policy, 11:1, DOI: 10.1080/20016689.2023.2216518

Qiu, T., Pochopien, M., Liang, S., Saal, G., Paterak, E., Janik, J., & Toumi, M. (2022). Gene Therapy Evidence Generation and Economic Analysis: Pragmatic Considerations to Facilitate Fit-for-Purpose Health Technology Assessment. Frontiers in Public Health, 10, Article 773629. DOI: 10.3389/fpubh.2022.773629

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