With billions of dollars and a decades-long epinephrine reign on the line, Mylan’s controversy-laden EpiPen story may have one major plot point: a small plastic cap.
To protect its monopoly, Mylan petitioned the FDA last year to reject a generic from Teva Pharmaceutical Industries. Teva's copycat was not equivalent, Mylan said, and shouldn't be eligible for approval.
In what way? Mylan cited EpiPen’s one-cap design, which releases at the push of a button, versus Teva’s device, which must be uncapped before use. A removable cap such as Teva’s could cause confusion, Mylan said, especially for patients dealing with an emergency.
The details of Teva's rejection aren't public, so there's no way of knowing whether the cap played a role. But it wouldn't be the first time that a delivery device kept copycat drugmakers at bay. GlaxoSmithKline, for instance, has enjoyed years of exclusivity on its respiratory blockbuster Advair, simply because its still-patented Diskus inhaler was too difficult to match.
In EpiPen's case, what's clear is that the FDA denied Mylan's citizen petition, because acting on that one feature of Teva's product would have subverted the agency's usual approval process, CDER chief Janet Woodcock said in a letter. But the agency left the door open to using Mylan's argument in rejecting the generic eventually.
When the rejection came, the FDA cited “certain major deficiencies." Neither Teva nor the agency has specified what, exactly, those deficiencies are. Cap or not? Either way, the FDA's rejection pushed Teva’s anticipated launch to 2017 or later.
Delivery devices tend to fall into this kind of trap. Because epinephrine is a drug well past its patent-protection period, Mylan's monopoly protection depends on the device’s design, not on the drug itself. But because EpiPen is both a drug and a medical device, it falls between those two departments of the FDA, resulting in a regulatory gray area.
EpiPen’s design is patent-protected until 2025, making the one-cap method (among other design elements) the one to either match, beat or prove immaterial. In its rejected petition, Mylan claimed “there is a real risk that the device will be misused, and that delivery of the drug will be delayed or completely missed, which can have lethal results.”
Now, amid scrutiny from analysts, lawmakers and a public incensed by price hikes amounting to 400% since 2009, it’s possible the FDA or Mylan will be forced to provide more answers about rejected generics. Senators Susan Collins (R-ME) and Claire McCaskill (D-MO) called for an “urgent briefing” with Mylan CEO Heather Bresch about the price hikes, and 5 senators wrote the FDA to question decisions made about competitive products.
The House Committee on Oversight and Government Reform also stepped in this week; it officially asked Bresch to hand over documents, and Ranking Member Elijah Cummings is calling for hearings next month.
It was a device problem that swept another EpiPen rival aside, too. Injector issues plagued Sanofi’s approved Auvi-Q competitor, which the company pulled last year after dosing malfunctions surfaced. Sanofi's partner on the med, Kaléo Pharma, says it's weighing its options for the product's future.
Meanwhile, Mylan is one of the generics makers targeting Advair, now that the tricky-to-copy Diskus device is nearing the end of its patent life. In February, the FDA accepted Mylan's application for approval, with a decision set for next March.
There's no guarantee it will win a quick clearance, however. Like Teva's EpiPen copy, Mylan's Advair knockoff might get knocked back on its first try. "[O]ur view is that it is tough to see such complex drug-device as first round approval," Bernstein analyst Ronny Gal wrote when Mylan announced the Advair move. Instead, he thinks the first quarter of 2018 is more likely for a rollout--perhaps around the same time Teva finally gets to launch its epinephrine injector.
- here's Bloomberg's take
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