ICER Issues Final Report and Policy Recommendations Regarding Treatments for Duchenne Muscular Dystrophy

— Public meeting reveals tensions inherent around high-priced treatments that lack adequate evidence of efficacy —

BOSTON, August 15, 2019 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report and Report-at-a-Glance assessing the comparative clinical effectiveness and value of the corticosteroid deflazacort (Emflaza®, PTC Therapeutics), and two exon-skipping therapies — eteplirsen (Exondys 51™, Sarepta Therapeutics) and golodirsen (Sarepta Therapeutics). ICER’s report on these three treatments for Duchenne muscular dystrophy (DMD) was reviewed at the July 2019 public meeting of the New England Comparative Effectiveness Public Advisory Council (NE CEPAC), one of ICER’s three independent evidence appraisal committees.

“DMD is a devastating disease,” said David Rind, MD, ICER’s Chief Medical Officer. “Parent testimony shared throughout the day provided a window into the hope and frustration that families are feeling as new treatments become available. In the case of deflazacort, we heard about how an inexpensive drug that was available overseas for years and could be easily brought into the US became unaffordably expensive with FDA approval when the US manufacturer massively increased its price. With eteplirsen, we heard about the hopes of parents that the treatment is beneficial. However, the wholly inadequate evidence base from the manufacturer has created such doubt that payers, faced with the outrageously high price charged by the manufacturer, have created extremely narrow coverage policies; no other country has even approved the treatment. We are left where no one can know whether a useful therapy is being administered to a small number of children while others around the world are denied therapy by payer barriers and regulatory approval, or whether the patients receiving eteplirsen are being given a useless, high-priced treatment. Three years after approval, the manufacturer has provided no high-quality evidence of benefit, many patients and families are surely losing out, and only the manufacturer truly benefits from this deplorable situation. Families and patients with DMD deserve better.”

During the meeting, a majority of CEPAC members voted that the evidence suggests that deflazacort achieves a net health benefit over prednisone, a more affordable corticosteroid. However, the panel did not find sufficient evidence to show a net health benefit of either eteplirsen or golodirsen over supportive care alone. During their deliberation, panel members also weighed the therapies’ other benefits and contextual considerations, highlighting that all three therapies target a condition of high severity and a high lifetime burden of illness, and that the use of deflazacort may reduce caregiver burden.

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. Still, after considering all of the evidence as well as the patient input on the non-clinical factors associated with these treatments, an overwhelming majority of the CEPAC voted that both deflazacort and eteplirsen represent a low long-term value for money. The CEPAC did not vote on golodirsen’s long-term value for money because the treatment’s price is not yet known.

To reach commonly cited cost-effectiveness thresholds of $100,000-$150,000 per Quality Adjusted Life Year (QALY) gained, despite assumptions felt to be very favorable for deflazacort, ICER’s evaluation found that an upper bound on deflazocort’s annual net price would need to be between $19,900-$31,700, representing a 73-83% discount off the treatment’s current Wholesale Acquisition Cost. 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. At its current cost of more than $1 million per year, eteplirsen would still far exceed commonly cited cost-effectiveness thresholds even if the most favorable assumptions were granted around the potential efficacy of the treatment.

Key Policy Recommendations  

Following the voting session, a policy roundtable of experts – including clinicians, patient advocates, and payer representatives – convened to discuss the implications of the evidence for policy and practice. Sarepta Therapeutics and PTC Therapeutics were invited to join, but both companies declined to participate. Key recommendations stemming from the roundtable discussion include:

  • Patient groups and clinicians should work with manufacturers early in the design of clinical trials to embed the expectation that patient-centered outcomes will be measured in key trials and that the company will bring an effective drug to market at a price that aligns fairly with the demonstrated benefits for patients.
  • To balance early access with the need for fair pricing and ongoing evidence development, drugs granted accelerated approval should be priced closer to the marginal cost of production until clinical benefits are proven.
  • Given the substantial remaining uncertainty regarding the benefits of these treatments in certain subpopulations and their high cost, it is reasonable for insurers and other payers to develop prior authorization criteria to ensure prudent use.

ICER’s detailed set of policy recommendations, including considerations for establishing prior authorization criteria, is available in the Final Evidence Report.

About ICER 

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.