Long after it arrived elsewhere, Emflaza (deflazacort) became the first corticosteroid that the U.S. Food and Drug Administration approved to treat all forms of Duchenne muscular dystrophy — in February 2017.
But its U.S. introduction was far from smooth. In fact, it took three more months and a change of ownership before it became available.
To better understand how Emflaza can benefit DMD patients, and the reasoning behind its pricing structure, Muscular Dystrophy News spoke with Braden Parker, vice president and general manager of PTC Therapeutics in the United States, and Jane Baj, vice president of corporate communications.
PTC bought the rights to Emflaza from Marathon Pharmaceuticals in April, in the midst of a controversy over its price. The company, which is awaiting an FDA decision on another DMD drug, Translarna (ataluren), specializes in rare disease research and treatments. It has worked closely with the DMD community for about 20 years.
Both steps — the FDA approval and PTC’s acquisition of the rights to Emflaza — were welcomed. Corticosteroids like deflazacort — Emflaza’s chief ingredient — have been used for years to treat inflammation in DMD patients worldwide. And Emflaza, like its generic, has shown considerable anti-inflammatory and muscle benefits in the clinical trials that led to its approval.
“At its core, the premise of Emflaza is to work against that inflammation across the entire spectrum of the disease and the course of the disease, and that has an effect on the ability to retain muscle and improve strength, and retain muscle function over time,” Parker said, referring to the drug’s FDA label. Corticosteroids are “the best kind of standard of care out there.”
Because its chief ingredient is in widespread use at considerably lower cost elsewhere, the U.S. introduction of deflazacort as Emflaza — with a brand-name drug’s price tag — continues to cause waves, however.
When PTC purchased Emflaza, its first move was to reduce Marathon’s $89,000 yearly price per patient to about $35,000 per year. But that price runs on a per-patient weight structure, and the $35,000 annual estimate applies only to boys who weigh up to 25 kg, or about 55 lbs.
Among objections quickly voiced were that a weight gain linked to steroid treatment could leave families of older boys — who can weigh as much as 100 kg (about 220 lbs) — paying more under the PTC pricing structure than under Marathon’s.
Parker discounts such concerns, noting that a huge gap exists between list and patient prices. Partly, he said, that’s a reflection of the “complexities of the U.S. healthcare system” and how a list price is translated down the line.
It’s also partly a reflection of Emflaza itself and how it is used, he said. “I think if you’re looking at it from a paper exercise, I see how maybe they get to that point. But in practical reality, it doesn’t seem to happen that way in how they’re prescribing the drug overall,” he said.
Although its label specifies a dose of 0.9 mg of Emflaza per kilogram of weight each day, physicians often do not rigidly comply with this when prescribing the drug.
“What we’ve seen in real clinical practice is that as patients gain weight, the dosing structure changes overall, and actually they’re getting dosed a lower mg/kg as weight goes up, and sometimes even lower than a lighter-weight patient,” Parker said. “So, you can have some situations where they’re dosing on weekends — high-dose weekends they call it — or every other day.”
More important is the immense difference between what patients pay out-of-pocket for a treatment and its list price, Parker said. “And I think there’s where we’ve [PTC has] made a real commitment to minimize or eliminate any out-of-pocket expenses for Emflaza patients or their families,” he added.
The Emflaza Cares program, developed by Marathon and continued under PTC, has various options for people with private and public insurance, as well as the uninsured. The program now ensures that most people pay little, if anything, for Emflaza. And that, according to Parker, is more beneficial than having to pay $1,200 or more for the generic, deflazacort.
Before Emflaza’s approval, patients could import generic deflazacort from Canada or Europe for, reportedly, as low as $1,200 a year. But few did, Parker said, possibly because its price as an unapproved treatment was borne entirely by a patient’s family.
“By our calculations, we thought that 10 percent or less of the U.S. population of Duchenne boys was able to access deflazacort,” he said. “That was part of the reason why we were so excited to take on this drug and this launch: It expanded the access for all. Particularly for those who weren’t able to afford to import it.”
“And the patients who were paying out-of-pocket are now paying little to nothing. So they’re seeing a savings,” Baj added.
“What we want to do at PTC is make sure that these decisions that are made between patients and physicians are clinical ones and not financial ones. So we’ve put all of these different support programs in place through EmflazaCares to ensure that happens,” said Parker, including a bridge program aimed at those who had previously imported deflazacort.
Although a patient may never see the full cost of a treatment, it exists. The price of Emflaza is significantly higher than prednisone, an approved glucocorticoid for DMD. The difference could prompt private insurers to require that a patient must fail to benefit from prednisone before obtaining access to a potentially better treatment.
At least one insurer, Blue Shield of Northeastern New York, has such a system in place. But Parker believe this will be a limited problem. Most patients, he noted, have already been treated with prednisone, and are unlikely to be told to return to it.
“We haven’t seen any current Emflaza patients having to go back on prednisone,” he said, adding that it could be a possibility with those who have had no exposure to steroids. Such patients would, of course, include all newly diagnosed Duchenne boys.
Rather, he said, a more important focus is educating insurance companies about the disease. Many insurers are not familiar with rare conditions like Duchenne, which he said affects about 9,000 boys in the United States. Initial plans for Emflaza coverage could change as insurers gain a better understanding of the drug and its benefits “over the course of the disease.”
Parker did not discuss the cost of Emflaza tablets, which are available at strengths ranging from 6 mgs to 36 mgs, or the cost of its liquid suspension, other than to note that prices rise with strength. But in a follow-up email, PTC said Emflaza’s wholesale acquisition costs were $43.60 for 6 mg tablets, $130.80 for 18 mgs, and $243.00 for 36 mgs. A wholesale acquisition cost, or WAC, is a drug maker’s list price to wholesalers.
Wholesale prices under a Missouri public health program, the only state that reports Emflaza’s WAC online, differed slightly. The Missouri prices as of July 1 were $44.046 for a 6 mg tablet, $132.142 for 18 mg, and $245.430 for a 36 mg tablet. This is equivalent to $6.8–$7.3 per mg for Emflaza’s various tablet strengths, and its liquid suspension was about $9.8 per mg.
But costs likely differ among states, and the drug’s use is not continuous — so annual costs can vary widely, and WAC does not take discounts into consideration.
Still, these prices may contribute to the ongoing debate about U.S. treatment costs, particularly for rare diseases.
Efficacy and benefits
PTC used deflazacort as a control-group therapy in a clinical trial of another treatment it developed, Translarna (ataluren), which European regulators have since approved. The ACT DMD Phase 3 clinical trial (NCT01826487) assessed whether Translarna could address an underlying mutation in Duchenne. The control group received either deflazacort (53 patients) or prednisone (62 patients) as part of standard of care.
PTC reported at the International Society for Pharmacoeconomics and Outcomes conference in May that deflazacort led to a significantly smaller decline in boys’ exercise capacity, a shorter time for them to climb four stairs, and better sports or physical functioning, as measured with a quality of life assessment.
Other results the company reported at the Boston event were close to significant, including the time it took for boys to rise from a lying to a standing position.
“One of the reasons we were so excited to get Emflaza, when we initially purchased it from Marathon, is because we had the ability to look into our own data,” Parker said. And what the company saw in the trial was “a product in Emflaza that could make a huge diffrence in the lives of Duchenne patients and families across the board.”
Reports from various clinical trials also indicated that deflazacort, or Emflaza, led to less patient weight gain than prednisone — always a concern with long-term steroid use. But specifics can be hard to come by, and Parker did not go into statistics from trials conducted by Marathon or others.
Data that Marathon provided to Muscular Dystrophy News months ago showed that a small study, published in 2000, indicated that deflazacort triggered lower weight gain, potentially benefiting movement capability. This was the only difference in a comparison of 18 Duchenne patients treated with deflazacort or prednisone.
A larger and pivotal study — which included 196 Duchenne patients — compared the two drugs to each other and to a placebo. The data, which was apparently never published, also linked deflazacort to less weight gain.
Working to get deflazacort approved in the United States, Marathon further analyzed results of that Phase 3 trial, which was performed in the 1990s. The difference in weight gain after 52 weeks of treatment was significant — 7 to 8.6 kg, depending on the deflazacort dose used.
The analysis reported other crucial differences between the treatments as well.
Deflazacort was linked to better muscle strength. Numerically superior results compared with prednisone also included lower rates of steroid-linked cushingoid and psychiatric side effects, and better preservation of lung function among 45 boys who had lost walking ability. Cushingoid effects include redistribution of body fat, bone mineral loss, and behavioral changes.
A statistically significant difference favoring deflazacort was seen both in weight gain and a timed functional test in which boys climbed four stairs.
Earlier registry data also indicated that boys on deflazacort retained their ability to walk longer than those on prednisone.
That data was key, Parker said, to PTC’s decision to engage with the Duchenne community on a new level — paying for the right to deliver Emflaza to patients across the U.S. — and to its recognition of Emflaza’s value as a treatment that not only delays the loss of one capacity but helps to do the same with others.
“What we’ve seen over time within the study of Duchenne,” he said, “is that loss of one milestone correlates to the loss of others. So if you’re able to preserve the ability to walk longer, that typically correlates to the ability to feed oneself longer, the ability to breathe without ventilation longer, and so on … It has a long-term lasting effect in this disease.”
Emflaza’s use is increasing, he said, with over 700 patients now prescribed it, including a number who were importing deflazacort previously. It is available in over 40 states, and roughly 45 Medicaid plans approve it — statistics that meet, or exceed, the company’s expectations since its May introduction.
Meanwhile, PTC is preparing for the possible U.S. launch of another Duchenne therapy this year, Translarna, already conditionally approved in the EU. An FDA decision is expected in October.
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