Translating DMD Clinical Trial Findings to Real-World Application Discouraging

Progress within the Duchenne muscular dystrophy (DMD) space continues to encounter roadblocks when attempting to translate clinical trial findings to real-world settings, according to new study results published in JAMA Network Open.

Study investigators were concerned about the substantial financial burden payers incur from FDA-approved medications when they saw high rates of treatment discontinuation among patients within 12 months of novel treatment initiation. Their principal outcomes of interest were health care costs and drug discontinuation post pivotal trial approval among routine care patients, with commercial insurance (n = 93) or Medicaid (n = 130), who initiated treatment with 1 of 4 novel DMD medications following their FDA approval: eteplirsen, golodirsen, viltolarsen, and casimersen. Data for patient claims came from Merative MarketScan (n = 58), Optum’s Clinformatics Data Mart Database (CDM; n = 35), and Medicaid.

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All patients were followed for the year after their first day of medication use, and discontinuation was considered a gap in usage of 1 month, with a 30-day exposure grace period. The ages varied widely, with the preapproval pivotal trial population (n = 106) having a mean (SD) age of 8.5 (2.0) years vs 12 years and older for the postapproval population. In addition, there were no female patients in the pivotal trials or identified within MarketScan, while the CDM and Medicaid populations comprised 2.9% and 1.5% female patients (P = .50).

“Since the FDA-approved indications for novel DMD drugs were not limited to a particular subset of patients with DMD, the population prescribed these drugs in routine clinical care may differ from the patients studied in the drugs’ pivotal clinical trials, raising further questions about the drugs’ efficacy,” the authors wrote. “Previous research has found similarities between patients with DMD and commercial insurance and those with Medicaid coverage, but differences in relation to the costly new medications have not been studied.”

Overall, the most common corticosteroid in use by patients initiating novel DMD treatment in this study was “any,” at 98.1% of the trial population, 55.2% of the MarketScan population, 45.7% of the CDM population, and 64.6% of the Medicaid population. Cardiac medication had the highest rate of use by those with Medicaid coverage (52.3%) vs it being least used by the preapproval pivotal trial population (22.6%). Eteplirsen was initiated far more by the postapproval population (91.4%-100%) vs the pivotal trial population (7.5%), and golodirsen and viltolarsen were only used by the pivotal trial patients and those identified in MarketScan.

Of the progression stages of DMD that were seen at baseline between the pre- and postapproval populations, no instances of stage IV disease were seen in the pivotal trial population—just stage 1/2 or stage 3—while this disease stage was seen in 14.9% of the MarketScan, 25.8% of the CDM, and 27% of the Medicaid populations (P < .001).

Across the 3 postapproval groups, mean (SD) payer cost for the novel DMD treatments ran the gamut. Payers for the patients identified through MarketScan paid the most by far, $634,764 ($607,101), which comes in at 65% more than those with Medicaid coverage ($384,023 [$1,165,730]) and 32% more than those identified by CDM ($482,749 [$582,350]). Those with Medicaid coverage, however, stayed on their novel treatment the longest: a mean (SD) of 7.2 (4.3) months compared with 6.1 (4.4) and 6.9 (3.9) months for those in MarketScan and CDM, respectively.

Following novel DMD treatment initiation, CDM had the highest rate of insurance disenrollment vs MarketScan and Medicaid, respectively: 22.9% vs 20.7% and less than 8.5%. The authors also noted that more patients with later-stage disease (stages 3 and 4) vs early-stage disease (stages 1 and 2) discontinued DMD treatment in MarketScan and CDM.

“The high discontinuation rates of novel DMD treatments found in our study merit further investigation,” the authors stressed. They attribute this to such potential challenges as inadequate finances, safety concerns, comorbid health conditions, and lack of data on long-term benefits and cardiac function improvements.

Future studies of novel DMD treatments, they recommend, should focus on how insurance coverage changes (ie, switching from private to Medicaid coverage) may be influenced by high DMD treatment costs; have trial populations that reflect the real-world populations investigative agents will be used among; assess clinical effectiveness and safety of novel DMD treatments in older patients who identify as a racial/ethnic minority and have later-stage disease; and how access and equity issues influence treatment decisions.

Reference

Hong D, Avorn J, Wyss R, Kesselheim AS. Characteristics of patients receiving novel muscular dystrophy drugs in trials vs routine care. JAMA Netw Open. 2024;7(1):e2353094. doi:10.1001/jamanetworkopen.2023.53094