At the end of last month, the Institute for Clinical and Economic Review, the independent non-profit research institute that analyzes the value of drugs, issued a draft report on the value and effectiveness of Duchenne muscular dystrophy drugs, reigniting controversies over these treatments.

The draft report from ICER examined Sarepta’s eteplirsen and its experimental drug golodirsen, which is under review at the U.S. Food and Drug Administration, as well as PTC Therapeutics’ steroid deflazacort.

Both eteplirsen and deflazacort were subjects of their own past controversies. Marathon Pharmaceuticals, which won approval for deflazacort in the United States, found itself entrenched in a public controversy over its $89,000 a year price for the drug. DMD patients in the United States had been buying the drug from Canada and the United Kingdom, where it has been available for about $1,000 a year. It was developed as an alternative to the steroid prednisone with less pronounced side effects.

Congressional critics held out Marathon as an example of pharmaceutical price gouging. It was a bad enough case that even the trade group PhRMA, whose CEO had been on its board, offered a rebuke of the company. Marathon sold the drug to PTC Therapeutics and wound down the company. ICER lists the drug’s current annual cost at $62,900.

Eteplirsen was the subject of a different controversy. Despite its much higher price tag (the dosing of the drug is dependent on the weight of the patient, and ICER lists the price as high as $892,000 a year), it was the debate around its approval that raised eyebrows.

An FDA advisory panel voted 7 to 6 that the company failed to demonstrate the drug was effective. FDA staff also voiced strong opposition to approving the drug based on the evidence provided, or lack thereof. Nevertheless, with pressure from the patient community, Janet Woodcock, director of the Center for Drug Evaluation and Research, pushed the drug through arguing that with no alternatives available to patients, the agency needed to be flexible.

It doesn’t take a deep knowledge of pharmacoeconomics to guess how these drugs might have fared within the draft ICER report with regards to their cost-effectiveness. ICER found the underlying evidence for evaluating the drugs “sparse.” Nevertheless, it said deflazacort is projected to have high costs relative to its benefits and that eteplirsen (and golodirsen if its priced similarly) had “no plausible treatment effects” that would make it reach cost-effectiveness below $150,000 per quality-adjusted life year.

Sarepta fired back at the ICER draft report. It called the institute’s approach “fatally flawed” in evaluating treatments for rare and genetic diseases. Because of that, it said it would not participate the organization’s reviews “until it adapts its model to address the inherent limitations and biases that compromise its evaluations of therapies intended to treat patients with serious, rare diseases.”

“To the extent ICER’s evaluations are taken seriously, no company would be able to attract investment to fund the development and manufacture of treatments for these rare diseases,” the company said. “Through its conclusions, ICER sends a clear message to innovators that developing rare disease therapeutics is not worth the effort, and to patients – often children who are dying with no other treatment options – that their lives are not worth the investment.”

The ICER report should be a reminder to rare disease patients and drug developers that regulatory agencies no longer represent the finish line for a therapy. Once a company wins approval to market a drug, payers still must be willing to pay for them if patients are ultimately to benefit.

That means that treatments must not only be considered safe and effective, but also provide value for their costs. While there is need for a robust discussion on how to properly determine the value of rare disease therapies, having adequate data to make that case will be essential.

Within the rare disease community there is a sense that there’s a fragile balance between pharmaceutical industry interest in developing rare disease therapies and the ability to command high prices for products. But if you speak to investors in the sector, they will express confidence that payers will continue to pay the high cost innovative therapies command if they deliver meaningful benefits to patients.

There is a case to make for broadening the framework for determining the value of rare disease therapies as benefits to patients that are meaningful may not be fully recognized by payers and treatments can have significant impact beyond the individual patient given the toll these diseases often have on caregivers and families. Rare disease drug developers have begun to make such cases, but it’s unclear how receptive payers will be to such arguments.

And it’s going to take more than righteous indignation to make the case for the value of a rare disease therapy. To borrow from Sean Connery’s Jim Malone in the Untouchables, you don’t bring righteous indignation to a gunfight, at least not without data to back it up.

The draft report will be open to public comment until 5 p.m. ET on June 18, 2019. ICER may revise key assumptions and findings, which will be published on July 11, 2019.  The report will be subject of a public meeting of the New England Comparative Effectiveness Public Advisory Council July 25, 2019.

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