- The Institute for Clinical and Economic Research, a drug cost watchdog often referred to as ICER, doesn't anticipate the earliest therapies for a rare muscular disease being cost-effective enough to warrant their current or expected prices.
- In a new report, ICER took a look at three treatments for Duchenne muscular dystrophy, or DMD. They were PTC Therapeutics' Emflaza, a corticosteroid with a list price of $90,700; Sarepta Therapeutics' Exondys 51, an antisense oligonucleotide that carried a list price of $300,000 following its approval in late 2016; and Sarepta's golodirsen, another antisense oligonucleotide set to receive a U.S. approval decision in August.
- ICER compared the costs of best supportive care and prednisone — a corticosteroid commonly used in DMD — to the costs of Emflaza, and found the latter drug has "very high costs relative to its benefits for patients and families." For Exondys 51 and golodirsen, which ICER said lack robust clinical data and/or pricing information, there weren't any treatment effects that would make the therapies hit cost-effectiveness thresholds below $150,000 per quality adjusted life year (QALY), according to the report.
Patients with DMD have genetic mutations that prevent their bodies from generating a protein, called dystrophin, vital for muscle strength and function. Over time, these patients lose the ability to walk or move independently, and by their 20s and 30s can experience fatal respiratory or heart complications.
Sarepta secured the first Food and Drug Administration OK for a DMD therapy in 2016 with Exondys 51 (eteplirsen). The accelerated approval, however, was considered controversial given the shaky efficacy data seen in clinical testing in patients amenable to exon 51 skipping.
In one study of a dozen boys with DMD, there was no statistically significant difference in dystrophin-positive fibers seen between patients on placebo and those receiving a high dose of eteplirsen. Patients receiving a lower dose over 24 weeks did show a greater change from baseline compared to the placebo group, but the amount of dystrophin-positive fibers still remained miniscule.
Notably, that trial extended for another four years. Results showed the average level of dystrophin among 11 of the 12 boys was 0.93% of the level seen in healthy subjects after 180 weeks.
Exondys 51 didn't stay the sole marketed treatment for DMD for long. Regulators approved PTC's Emflaza (deflazacort) for the indication in 2017, though that also came with considerable criticism.
Golodirsen may provide a third option before the end of the summer, in patients who are amenable to exon 53 skipping.
ICER acknowledged there were many assumptions it had to make in its analysis of the three drugs, such as the price of golodirsen — which it expects to be in-line with that of Exondys 51. The group also noted that the underlying evidence supporting Emflaza, Exondys 51 and golodirsen "remains sparse."
All three of the therapies, however, pose cost issues, ICER concluded.
ICER didn't do a cost-effectiveness analysis in the base case for Exondys 51 or golodirsen, citing "insufficient evidence to model treatment effects." Still, the group determined there were "no plausible treatment effects" that would get Exondys 51 — and, somewhat by extension, golodirsen — to reach a cost-effectiveness threshold below $150,000 per QALY at its current price.
Average annual per-patient budget impact
|List price||Net price||Price to reach $150,000/QALY||Price to reach $100,000/QALY||Price to reach $50,000/QALY|
As for Emflaza, ICER calculated that using it over prednisone represented an additional per-patient cost of between $42,000 and $61,000, depending on whether list or net price is being used.
ICER did find that regardless of list or net price, Emflaza wouldn't exceed a five-year annualized potential budget threshold of $819 million, though that's largely "due to the relatively small number of patients eligible for treatment each year."