Spending on Targeted Therapies for Duchenne Muscular Dystrophy

Abstract

This study estimates public and private spending on genetically targeted treatments for Duchenne muscular dystrophy during years in which the drugs were marketed without completed confirmatory studies.

Since 2016, the US Food and Drug Administration (FDA) has granted accelerated approval to 5 genetically targeted therapies for Duchenne muscular dystrophy. Each approval was based on studies that showed small mean increases in patients’ muscle dystrophin levels, which the FDA deemed reasonably likely to predict clinical benefit.¹ Confirmatory trials for 3 of these drugs (eteplirsen, golodirsen, and casimersen) have been delayed and remain incomplete. A confirmatory trial of a Duchenne muscular dystrophy gene therapy, delandistrogene moxeparvovec-rokl, failed to meet its primary end point of improved functional mobility scores compared with placebo.² A trial of viltolarsen has been completed but results have not been publicly released.

Despite limited evidence of efficacy,¹ these new Duchenne muscular dystrophy products are expensive. Eteplirsen can cost more than $1 million per year and delandistrogene moxeparvovec-rokl costs $3.2 million for a 1-time treatment. Fewer than 50 000 people in the US have Duchenne muscular dystrophy,³ and not all are eligible for these medications; still, the high prices of these drugs can lead to substantial spending. This study estimated public and private spending on genetically targeted treatments for Duchenne muscular dystrophy during the years in which these drugs have been marketed without completed confirmatory studies.

Methods

We included the following 3 Duchenne muscular dystrophy drugs that were approved from 2016 to 2022: eteplirsen, golodirsen, and casimersen (Table). We excluded delandistrogene moxeparvovec-rokl because it was approved after our study period and viltolarsen because the drug’s owner (a private company) has not published US revenue data. Net Medicaid spending on this drug was less than $10 million in 2021, so its exclusion was unlikely to substantially affect the results. We compiled manufacturer-reported annual US net sales from 2016 through 2022 from SSR Health. Net sales include rebates and statutory discounts to Medicaid or 340B entities.

Table. Genetically Targeted Therapies for Duchenne Muscular Dystrophy.

Drug name	Manufacturer	Date of accelerated approval	Original FDA deadline to complete confirmatory trial	Status of confirmatory triala
Eteplirsen (Exondys 51)	Sarepta Therapeutics	September 19, 2016	November 2020	Active, not recruiting; expected completion November 2024
Golodirsen (Vyondys 53)	Sarepta Therapeutics	December 12, 2019	April 2024	Active, not recruiting; expected completion October 2025
Viltolarsen (Viltepso)	NS Pharma	August 12, 2020	July 2024	Completed October 2023b
Casimersen (Amondys 45)	Sarepta Therapeutics	February 25, 2021	April 2024	Active, not recruiting; expected completion October 2025
Delandistrogene moxeparvovec-rokl (Elevidys)	Sarepta Therapeutics	June 22, 2023	September 2023	Completed October 2023c

^a As of January 31, 2024, according to ClinicalTrials.gov records (NCT03992430 [eteplirsen], NCT02500381 [golodirsen, casimersen], NCT04060199 [viltolarsen], and NCT05096221 [delandistrogene moxeparvovec]).

^b Although the trial has completed enrollment, results were not publicly released as of January 31, 2024.

^c A confirmatory trial of delandistrogene moxeparvovec failed to meet its primary end point, according to a press release from Sarepta Therapeutics on October 30, 2023.²

To understand the share of costs borne by taxpayers, we measured annual Medicaid and Medicare Part D spending from 2017 to 2021 using public dashboards; there was no reported spending on these drugs in 2016. We estimated net Medicaid spending by applying the statutory minimum rebate of 23.1% and net Medicare spending by subtracting non-Medicaid rebate estimates from SSR Health, which ranged from 3% to 15%. We projected Medicaid and Medicare spending in 2022, assuming that these programs accounted for a similar share of US sales as in 2017 to 2021. Analyses were conducted using Microsoft Excel version 2311. Spending estimates were converted to June 2023 US dollars using the Consumer Price Index for all urban consumers.

Results

Annual net sales for eteplirsen, golodirsen, and casimersen increased from $7 million in 2016 to $879 million in 2022, totaling $3.1 billion over this 7-year period. Estimated net Medicaid and Medicare spending on these drugs increased from $25 million in 2017 to $327 million in 2022, totaling $1.2 billion (Figure). Of this total, Medicaid programs spent $1.1 billion (34% of US net sales) and Medicare spent $104 million (3% of US net sales).

Figure. Estimated US Net Spending on Targeted Therapies for Duchenne Muscular Dystrophy, 2016-2022.

Dashed lines denote projected spending, assuming that Medicaid and Medicare represented a similar share of total US spending in 2022 as in 2017 to 2021.

Most US spending on these therapies during this period was on eteplirsen ($2.6 billion [82%]). US payers spent an estimated $301 million (10%) on casimersen and $263 million (8%) on golodirsen from 2016 to 2022.

Discussion

Duchenne muscular dystrophy–targeted therapies with limited evidence of clinical efficacy have cost the US health care system more than $3 billion, more than one-third of which was paid by Medicaid and Medicare. Most of this spending was for eteplirsen, the efficacy of which has yet to be determined in a confirmatory trial more than 7 years after the drug’s accelerated approval.⁴ This study had limitations. Net sales exclude supply chain costs, Medicare spending may be underestimated if SSR Health rebates are overestimated, and the FDA may have considered efficacy data that are not publicly available.

This analysis of Duchenne muscular dystrophy–targeted therapies sheds light on controversies relating to drugs’ limited preapproval evidence of efficacy, high prices, and delayed confirmatory trials. For example, more than half of the drugs granted accelerated approval from 2012 to 2021 did not complete confirmatory trials by the FDA’s deadline.⁵ As the FDA considers approving multimillion-dollar therapies with novel mechanisms of action and scant preapproval evidence of clinical benefit,⁶ policymakers should encourage timely completion of confirmatory trials and minimize financial risk in case treatments prove ineffective. Limiting Medicare and Medicaid reimbursement for accelerated approval drugs and alternative payment contracts for cell and gene therapies should be considered.

Section Editors: Kristin Walter, MD, and Jody W. Zylke, MD, Deputy Editors; Karen Lasser, MD, Senior Editor.

Supplement.

Data sharing statement