The Mylan NV pile-on over the U.S. pricing of its life-saving Epipen is putting other players, including the FDA, on the defensive in a Senate investigation, while unintentionally showcasing the importance of a delivery device.

In the opening play of a bipartisan investigation into a 480 percent pricing increase, over several years, of the auto-injector that counters severe allergic reactions, members of the Senate Judiciary Committee wrote to FDA Commissioner Robert Califf Wednesday wanting answers, by Sept. 8, about the market impact of the FDA's role in approving Epipen competitors.

"We are concerned that Mylan has not faced much competition for its product," committee Chairman Chuck Grassley (R-Iowa) said in the letter, which also was signed by Ranking Member Patrick Leahy (D-Vt.) and Sens. Amy Klobuchar (D-Minn.), Richard Blumenthal (D-Conn.) and Ron Johnson (R-Wis.). (Johnson is not a member of the Judiciary Committee.)

Pointing out that the Epipen (epinephrine injection) has been in use since 1977, the letter questioned the lack of competition, asking the FDA to identify barriers that may exist to approving safe alternatives. The senators noted that Sanofi SA recalled Auvi-Q in October 2015, giving Mylan a near monopoly. Epipen's market domination continued when the FDA refused in February to approve a generic from Teva Pharmaceutical Industries Inc. (See BioWorld Today, Aug. 24, 2016.)

Significant work is needed to address the major deficiencies the agency cited in its complete response letter, but the Jerusalem-based Teva reported in June that it has found a way forward and that the FDA is not against a generic Epipen, according to Randall Stanicky, an analyst with RBC Capital Markets LLC. Teva hopes to get its generic approved late next year or early in 2018.

Meanwhile, Epipen doesn't have the market entirely to itself. Impax Laboratories Inc.'s Adrenaclick auto-injector can be substituted for Epipen in 21 states, Stanicky said. However, Impax must tackle a supply hurdle. The Hayward, Calif., company is in the midst of a 12- to 15-month initiative to increase the supply of Adrenaclick. Stanicky expects a boost in supply next year.

Where it's available, Adrenaclick offers an affordable alternative to Epipen, with retail pharmacy prices, based on an advertised coupon discount, ranging from $145-$380 for a two-pack. In comparison, parents of kids with allergies have reported that they recently paid $500 to $600 for Epipens.

But Mylan's home field advantage isn't just availability. Ease of use and patient familiarity with the device have helped build Epipen's most valuable player status. When alternatives enter the game, they will have different injector devices, each of which will have its own instructions. Impax, for example, offers product trainers and an online training video for Adrenaclick. In an emergency, the potential for incorrect usage or the need to consult the instructions before using an unfamiliar device could delay treatment or cause an injury.

A 2012 American College of Allergy, Asthma, and Immunology study found that people who have been prescribed epinephrine tend to forget how to use a specific injector after about three months of not needing it.

NO CHANGE IN PRICE

Secure in its market position, Mylan's playbook in the Epipen scrimmage doesn't include lowering the U.S. price of the auto-injector. Instead, it announced Thursday that it's expanding its savings card and patient assistance programs. As a result, the savings card, which had knocked $100 off an insured patient's out-of-pocket cost, will now knock off $300. That means some insured patients who haven't met high deductibles will pay $200 to $300 for a two-pack.

However, the card is limited to three two-packs per prescription. And unless it includes a patient rebate, it won't help those who have already filled their prescriptions. Parents of children with life-threatening allergies usually buy several Epipens so they will be available at all times at home, school and with the child. Since the pens expire every year, they must be replaced annually. Many parents replace unused injectors at the beginning of the school year, which means they would have already filled their prescriptions by now. In fact, it is the sticker shock from that experience that ignited the current outrage.

In other countries, patients haven't experienced that sticker shock, and they have more options, according to the letter from the senators. It noted that two Epipens cost about $85 in France, $119 in the U.K. and $131 in Canada. In addition, Anapen, an auto-injector from Lincoln Medical, is available in all three countries at a comparable price. A third competitor, Alk-Abello AS' Jext, is available in the U.K. at $32 for one injector.

Even though the FDA is not directly involved in drug pricing, the senators questioned the Epipen price, reminding Califf that epinephrine is inexpensive – less than $1 per milliliter. Thus, epi kits, comprised of vials of epinephrine and syringes, are becoming a much cheaper choice for first responders, health care providers and even some patients. Consequently, the rising cost of Epipens over the past few years could be feeding a demand that's led to a shortage of other sources of epinephrine.

The senators observed that the FDA has included self-injectable epinephrine on its drug shortage list since 2012. According to the drug shortage database, several companies supply the drug in vials, ampules and prefilled syringes. A few of those companies have reported manufacturing delays and shortages, listing "other" as the reason. While it has vials and prefilled syringes available, Amphastar Pharmaceuticals Inc. reported an increased demand for both products.

In its response to the outcry over the price of Epipens, Mylan didn't mention an epinephrine shortage. Instead of trying to justify the increase, it again deflected the blame to changes in the insurance industry that are shifting more of the cost of drugs to patients. But patients aren't buying it. A Moveon.org petition that's circulating via social media had more than 200,000 signatures early Thursday.

The petition calls on Mylan CEO Heather Bresch to "stop price-gouging the millions of people who need an Epipen to save their lives." As background info for signers, the petition noted Mylan's most recent action, adding, "The company's 'solution' in the face of overwhelming public outcry is to offer more coupons. But it has not lowered the price ONE CENT. So keep the pressure up!"

CHECKING THE SLIDE

As a result of the public criticism and Senate scrutiny, Mylan (NASDAQ:MYL) once again saw heavy trading Thursday and its shares continued to slide, closing at $42.85. Two weeks ago, Mylan shares were trading at nearly $50.

The downward slide may have been checked by a few pieces of good news for the Canonsburg, Pa., company. Wednesday, the U.S. Patent Trial and Appeal Board ruled in favor of Mylan's inter partes review challenge of two related patents protecting Teva's Copaxone (glatiramer acetate injection) 40 mg/mL, helping to clear the way for a generic of the multiple sclerosis drug dosed three times a week. The board is expected to rule by Sept. 1 on a Mylan challenge to a third patent.

As one of the first companies to file a substantially complete ANDA containing a Paragraph IV certification for Copaxone 40 mg/mL, Mylan said it expects to be eligible for 180 days of marketing exclusivity in the U.S. upon FDA approval of its generic.

The other bright spot is the EMA's acceptance Wednesday of a marketing authorization application (MAA) for a biosimilar referencing Genentech Inc.'s Herceptin (trastuzumab). Mylan said the MAA may be the first accepted by the EMA for a trastuzumab biosimilar. It's also Mylan's second accepted MAA for a biosimilar developed in partnership with Biocon Ltd., of Bangalore. Last month, the EMA said it would review the partners' application referencing Amgen Inc.'s Neulasta (pegfilgrastim).

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