- Company argued that different design could confuse patients
- Teva has attempted to get approval for substitutable generic
The lack of a cheaper version of Mylan NV’s EpiPen shot may come down to a dispute between drugmakers over a plastic cap.
Unlike Mylan’s one-cap EpiPen, Teva Pharmaceutical Industries Ltd.’s proposed substitutable generic version has two caps, including a removable one that covers the spot where its needle extends. In a petition to the U.S. Food and Drug Administration, Mylan cited that difference as the key reason the agency should reject Teva’s generic -- which is exactly what happened in February of this year.
Nina Devlin, a Mylan spokeswoman, said the company asked the FDA to only approve the competing devices if they were truly equivalent, and wouldn’t pose a risk of confusing patients who were having an emergency. “We expressed our concern that the product may not meet the standards, and therefore presents distinct risks,” she said in an e-mail Wednesday. Denise Bradley, a Teva spokeswoman, declined to comment on the company’s conversations with the FDA.
The basic design of the EpiPen has been around since the 1980s, when doctors touted the then-new device as an easy way for patients to self-administer doses of epinephrine, a hormone synthesized about 100 years ago that’s long been used to treat serious reactions from bee stings and food allergies.
‘Difference in Design’
“The difference in design leads to a slight difference in operability,” said Ronny Gal, an analyst with Sanford C. Bernstein & Co. “Teva says, ‘Ours is good enough,’ and Mylan is saying it’s not.”
Mylan dominates the market for epinephrine auto-injectors, and its pens -- largely sold as a $600 two-pack -- now take in about $1 billion a year. That leading position is due in part to U.S. rules governing drugs that are administered via a device. While the drug inside the pen may be old, the patents governing design improvements to the auto-syringe in recent years aren’t.
Mylan is under fire for taking advantage of its market dominance to sharply raise prices. The company, which is run from Canonsburg, Pennsylvania, acquired the rights to sell EpiPen in 2007, when it cost about $57 per shot. Mylan this week said it will introduce its own generic version at $300 for a two-pack, half the current list price of the branded version. While the company’s practices prompted patient outrage and congressional investigations this month, the pen’s origins go back decades.
About forty years ago, Michael Mesa, now 69, was working as a technician at a company called Survival Technology that developed an auto-injecting syringe that would become the basis for EpiPen. It was originally used to administer the drug lidocaine for people with irregular heartbeats, Mesa said. Around the same time, the U.S. military also approached Survival Technology about using the device to administer treatments for chemical warfare, and NASA astronauts used the approach for nutrition delivery, according to an article from 1980 in the Journal of Asthma Research.
Mesa spent 42 years at the company, which through a series of deals ended up a subsidiary of Pfizer Inc. that now manufactures Mylan’s EpiPens. Later, he worked on changes to the device that improved its design. The pen now includes a non-removable needle cap that prevents users from accidentally pricking themselves or others. That advancement and others were patented in the last eight years, and Mylan argues they’re critical to the pen’s safety and functionality.
They also help protect the design from competition until 2025, an added benefit for Mylan.
Must Be Identical
A substitutable generic product, no matter how it’s administered, has to be interchangeable with the original, according to FDA rules. Teva’s two-cap version, made with Antares Pharma Inc.’s Vibex auto-injector, contains an extra step and slightly different directions for patients. Mylan argued that because of the design difference of the caps, a patient in distress might not be able to quickly operate Teva’s version that they’d been handed by their pharmacist instead of the original.
Mylan, in a January 2015 petition to the agency while Teva’s drug was under review, argued that “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.”
The FDA rejected Mylan’s petition in June 2015 because it hadn’t made a decision yet whether to approve Teva’s application as a whole. In denying Teva’s version of the pen in February 2016, the agency cited “major deficiencies” in the proposal, and Teva said it would likely be delayed until at least 2017.
Getting products like EpiPen -- or their generic equivalents -- through the agency isn’t always easy. It’s both a drug and a device, which means it falls into a gray area between the pharmaceutical and medical-device divisions of the FDA.
The agency declined to comment on the differences between Teva and Mylan’s products and whether the cap differences are the key to what’s holding up Teva’s application. The agency typically doesn’t comment on applications while they’re being reviewed.
On Aug. 24, as outrage over Mylan’s pricing grew, five Democratic and Republican senators, led by Chuck Grassley, the Iowa Republican, wrote the FDA asking about delays in approving a generic alternative.
“We are concerned that Mylan has not faced much competition for its product,” they said in the letter. “It is imperative to understand the FDA’s role with respect to EpiPens and its approval of generic equivalents that could help to increase competition and lower prices if introduced.”