— No price can be suggested as a fair value-based price for eteplirsen or golodirsen because no persuasive evidence yet exists to demonstrate the clinical effectiveness of either drug —

— For deflazacort, discounts of at least 73% from its list price would be needed to achieve commonly cited thresholds for cost-effectiveness —

— As with all treatments for ultra-rare conditions, judgments of overall value require consideration of contextual issues and broader benefits for patients and families; these additional factors will be discussed during a July 25 public meeting —

The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of two exon-skipping therapies to treat Duchenne muscular dystrophy (DMD) — eteplirsen (Exondys 51™, Sarepta Therapeutics) and golodirsen (Sarepta Therapeutics) — as well as deflazacort (Emflaza®, PTC Therapeutics), a corticosteroid.

“DMD is a progressive neuromuscular disorder that devastates the lives of children and the families who care for them, and better therapies are desperately needed,” said David Rind, MD, ICER’s Chief Medical Officer. “Unfortunately, there is no persuasive evidence that these exon-skipping therapies improve outcomes that matter to patients, including functional status, quality of life, or length of life. Eteplirsen has been on the market for three years and yet we still found notably inadequate data on patient outcomes. Corticosteroid therapy does improve outcomes in DMD, and there is some evidence that deflazacort may have larger benefits and smaller harms than prednisone; however, despite being developed decades ago and approved based on a trial from 1995, deflazacort’s US price appears far out of line with any believable added benefits for patients, and it is more than 50 times higher than what is paid in other countries. This apparent mismatch between evidence and price raises important concerns for patients, caregivers, and all other stakeholders in the health care system.”

This Evidence Report will be reviewed at an upcoming public meeting of the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), in Cambridge, MA on July 25, 2019. The New England CEPAC is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

Key Clinical Findings

Data on the exon-skipping therapies are extremely limited. Trials of eteplirsen and golodirsen show slight increases in levels of dystrophin, the protein that is affected in people with DMD, but this is of uncertain clinical significance. In the absence of data convincingly demonstrating improvement in function or outcomes, the evidence was insufficient to determine any net health benefit of golodirsen or eteplirsen.

Corticosteroids — including prednisone and deflazacort — are commonly used for treatment in DMD patients. Randomized trials and observational studies provide moderate certainty that deflazacort has comparable or better net health benefits when compared to prednisone. Deflazacort likely produces less undesired weight gain than prednisone but greater reductions in growth.

Key Cost-Effectiveness Findings

Even if eteplirsen were assumed to restore all patients with DMD to perfect health for an additional 40 years of life, at its current price it would still far exceed commonly cited cost-effectiveness thresholds. The same conclusion would apply to golodirsen if it is priced similarly to eteplirsen. In the absence of persuasive evidence demonstrating clinical effectiveness, ICER is unable to calculate value-based price benchmarks for eteplirsen or golodirsen.

The value-based price benchmark range for deflazacort is no higher than $19,900-$31,700 per year, which would require a 73-83% discount off the treatment’s Wholesale Acquisition Cost (WAC). This value-based price range is likely an upper limit as it involves very favorable assumptions around the benefits of deflazacort.

ICER’s value-based price benchmarks suggest a price range, net of any discounts and rebates, that aligns fairly with a treatment’s added benefits for patients over their lifetime. The ranges reflect commonly cited cost-effectiveness thresholds of between $100,000 and $150,000 per Quality-Adjusted Life Year (QALY) gained. To reach alternative thresholds of between $100,000 and $150,000 per Life Year Gained (LYG), deflazacort’s annual price would need to be within the range of $21,100-$33,500.

We note that for treatments of ultra-rare conditions like DMD, insurers and other decision-makers often give added weight to contextual considerations that lead to acceptance of prices higher than those that would meet traditional cost-effectiveness ranges.