Tag Archives: EpiPen

EpiPen.

After a yearlong delay, FDA approves EpiPen generics

The EpiPen is going generic.

EpiPen.

An EpiPen box.
Image credits Intropin / Wikimedia.

The U.S. Food and Drug Administration (FDA) approved the first generic version of the EpiPen and EpiPen Jr auto-injectors for allergic reactions. The devices, used to inject epinephrine in the emergency treatment of allergic reactions in adults, were mired in controversy as its producer, Mylan, applied ludicrous price increases to the life-saving devices.

Mylan’s CEO, Heather Bresch, eventually had to testify in front of the House Oversight and Government Reform Committee about the drug’s price increase back in 2016. You can read about the fallout in all its glory here and here.

The generic version should give patients an affordable alternative and break Mylan’s monopoly over this device. US-based Teva Pharmaceuticals gained approval to market its generic epinephrine auto-injector in 0.3 mg and 0.15 mg strengths. The company hasn’t provided any details about when the generics will hit the market or their planned price.

Off-brand, on point

“Today’s approval of the first generic version of the most-widely prescribed epinephrine auto-injector in the U.S. is part of our longstanding commitment to advance access to lower cost, safe and effective generic alternatives once patents and other exclusivities no longer prevent approval,” said FDA Commissioner Scott Gottlieb, M.D.

Patients with severe allergies can’t afford the luxury of not buying EpiPens; their life quite literally depends on it in the case of a severe allergic reaction (called ‘anaphylactic reactions‘). Life-threatening allergies can include reactions to insect bites or stings, foods, medications, latex, or other causes.

Allergic reactions typically affect a localized area of the body. Our immune systems react to a particular allergen, and specialized types of T and B (white) cells flood tissues with cytokine, interleukin-4, and antibodies in response; this is what causes allergic symptoms such as inflammation. Anaphylactic reactions take place pretty much the same way but affect the whole body. If left untreated, such a reaction can and often does lead to death.

Epinephrine (or adrenaline, it’s the same substance) works by reducing swelling in the airway and increasing blood flow in the veins.

Epinephrine.

Epinephrine.
Image via Wikimedia.

Needless to say, this puts patients in a tight spot when price hikes leave them — again, quite literally — unable to afford the devices. The FDA’s move is meant to protect exactly these people. Patients with severe allergies now have a lower-cost option for the treatment they need. Approval for the generic version should also “help protect against potential drug shortages”, the FDA explains.

“We remain committed to doing our part to provide scientific and regulatory clarity for sponsors seeking to develop complex generics, as well as prioritize the approval of medicines with little or no generic competition as part of our overarching effort to remove barriers to generic development and market entry of critically important medicines,” the Administration adds.

Products such as the EpiPen are known as ‘combination products’ — they consist of both a drug (epinephrine) and a device (the autoinjector or ‘pen’ itself). They’re more complicated to develop compared to regular drugs, and the FDA regularly takes steps to help guide industry through the process. The FDA dutifully requires adequate proof that combination products produce consistent, quality results before giving them the seal of approval.

However, this (alongside patent rights) also means that it’s hard for other agents to come up with a competitor product for even relatively simple devices such as the EpiPen. To their credit, the FDA is making efforts to streamline the process of getting a generic approved — for example, they announced the Drug Competition Action Plan last year, outlining the steps required to get such a generic to market.

And it seems to be working. The generics are the first competitors cleared by the FDA that are direct generic copies of the EpiPen. “Authorized generics” are basically the same as the branded product but don’t display the brand or manufacturer on their package. Companies may choose to sell an authorized generic at a lower cost than the brand-name drug product.

Other epinephrine auto-injectors, such as the Adrenaclick and Auvi-Q, are on the market but aren’t considered EpiPen generics.

“We’re applying our full resources to this important launch in the coming months and eager to being supplying the market,” Teva said in a statement.

Roughly one in 50 Americans experience anaphylaxis, according to the Anaphylaxis and Allergy Foundation of America. It’s not a one-time affair, either; anyone who goes through one anaphylactic episode always faces the risk of going through another one. These patients thus always carry an emergency dose of epinephrine with them at all times; many keep more than one dose handy.

The EpiPen conquered the market because it’s simple and quick to administer. All you have to do is take the pen, jam it in your thigh, and it automatically injects a dose of epinephrine to stop the allergic reaction.

EpiPen still expensive and critics should go “copulate with themselves,” Mylan chairman thinks

Oh boy, do I have a treat for you guys today. The kind that makes you breathe deeper, gets you feeling all hot and bothered inside, the kind of treat that really gets the blood boiling. Hope I didn’t give it away yet. You ready?

It’s corporate greed and gross indifference towards human suffering, of course! How quaint. Naturally, Mylan is the centerpiece of the show. So let’s dive right into it.

But first:

Meet Robert Coury. He’s a firm believer in self-love. You’ll see.
Image via YouTube.

 

A short recap

A while ago we fired a few shots at Mylan and its CEO Heather Bresch for the ludicrous price increases of the company’s signature EpiPen. She found herself in the ignominious position of testifying in front of Congress with the same credibility of a schoolgirl blaming the dog for eating her homework, then not being able to recall what the homework was.

The short of it is that Bresch wasn’t able to remotely justify the product’s 500% price increase since 2007 when Mylan acquired its patent rights. It also became apparent that the company strong-armed schools into effectively banning lower-cost alternatives from their nurse offices via the EpiPen4Schools program, all adding up to something which Rep. Tammy Duckworth rightfully called a “monopoly”.

To add a little Godfather (Godmother?) twist into the whole thing, schools were “strongly encouraged” or downright required to have anti-anaphylactic meds on hand following an unprecedented push by the National Association of State Boards of Education (NASBE) — which was headed since 2012 by Gayle Manchin, Bresch’s mother. Naturally, the schools weren’t informed of the blood ties between NASBE and Mylan when they were signing the deals.

“Eleven states drafted laws requiring epinephrine auto-injectors. Nearly every other state recommended schools stock them after what the White House called the “EpiPen Law” in 2013 gave funding preference to those that did,” USA Today reported on the issue.

Altogether, Congress had a lot of ‘slippery’ during the hearing and almost no hard answers — if you’ve missed it, here it is again, so you can give it a read. Because you’re going to need all the warm-up you can get for this next bit.

Anatomically incorrect

As you can probably tell, the whole thing basically pissed everyone off, except the shareholders. Mylan has had to deal with a very harsh backlash from customers, advocates, federal investigators, lawmakers, all the works, but the price of EpiPen is still not dropping. Which is puzzling, to say the least — what Mylan is doing is the economic equivalent of putting on the noose and handing the rope to the same people whose kids, friends, and relatives are dying to a peanut because they can’t shell out $609 on a pack of life-saving medicine. The parents, family, and friends of some 15 million of Americans.

It’s all terribly puzzling until you factor in that Mylan has, for all intents and purposes, a near monopoly on a vital product and/or hear about their creative take on marketing strategy. It’s all courtesy of The New York Times’ , who sat down with 10 of the company’s former mid-level executives and also talked with CEO Heather Bresch to pick their brains on the matter.

According to these former executives (all of whom asked to remain anonymous citing nondisclosure agreements and potential retaliation from Mylan), the company’s top brass fully expected a public outrage over its price hiking and planned to simply ignore it. These former execs say they’ve repeatedly raised concerns that the hiking amounts to “unethical profiteering” on the backs of patients with no other alternative, all the way back since 2014. And here’s where it gets really good:

“Over the next 16 months, those internal warnings were repeatedly aired. At one gathering, executives shared their concerns with Mylan’s chairman, Robert Coury,” Duhigg writes. “Mr. Coury replied that he was untroubled.”

“He raised both his middle fingers and explained, using colorful language, that anyone criticizing Mylan, including its employees, ought to go copulate with themselves. Critics in Congress and on Wall Street, he said, should do the same. And regulators at the Food and Drug Administration? They, too, deserved a round of anatomically challenging self-fulfillment.”

“When the executives conveyed their anxieties to other leaders, including the chief executive, Heather Bresch, these, too, were brushed off, they told me.”

I can only tip my hat to Mr. Duhigg’s impressive word taming skills. The point makes its way across nicely. Though I warmly invite Mr. Coury to show us all how it’s done.

Unethical is putting it mildly

EpiPen.

I’d suggest he start with one of these. Considering the price they’re going for it’s guaranteed to increase his self-worth.

You may be surprised to find that despite receiving around $160 million in compensation last year from Mylan, Mr. Coury declined to comment on the matter — who would have thought, right? Bresch luckily didn’t, and it’s from her we learn that Mylan is, in fact, “a pretty rare and unconventional company,” wholly dedicated to the consumer, delivering low-cost meds, snooze, snooze, snooze. It’s the broken healthcare system that’s bringing the company down, bringing prices up, and causing all this hardship for the people in need.

To back her words, she mentions the generic version of EpiPen, which Mylan released after their meltdown of a Congress hearing. A two-pack of these will take you back less than the brand-name two pack, but as always, there’s a caveat.

“When I asked my pharmacist for the generic EpiPen,” Duhigg recounts, “he told me that I would have to wait 90 minutes, until he could get my doctor on the phone to authorize the substitution. Then, he charged me $370 for the generics.”

A far cry from the $100-a-two-pack price the pens were sold for before Mylan got in on the business — and an inexcusable leap from the $35 EpiPencil Four Thieves Vinegar proved you can make at home. Even if that price was excusable, how many of us would be willing to wait for an hour and a half to get the cheaper pen when your kid can’t breathe back home? How enjoyable will that wait be when the generic kind is all you can afford, even if it means no food today, tomorrow, the whole week — maybe the week after that? Unethical profiteering seems too small a term when seen from this light, doesn’t it?

In the end, Mylan made some $1.1 billion in revenue every year from the EpiPen alone. And its CEOs are the highest paid in the industry. Shame and loathe be onto them. But I think it’s clear that left to their own devices, Mylan’s top brass won’t change. They don’t see any reason to. Change has to come from outside — affordable alternatives to the EpiPen (pills and auto-injectors) are slowly becoming available, and doctors need to start prescribing those (as well as other competing products) in place of what Mylan has to offer. Pharmacists, too, should guide customers to non-Mylan alternatives.

Because if they have an alternative to the EpiPen, all those hands holding the noose will have not only a motive but also a means to pull on the rope.

Epinephrine pill might break the EpiPen scandal and give patients their first valid alternative

An alternative to the EpiPen might soon make it to a pharmacy near you. An epinephrine tablet that dissolves under the tongue comes to shake auto-injectors’ monopoly on the market.

epipenLast month, Heather Bresch as CEO of Mylan went through a pretty harsh Congressional hearing to explain the skyrocketing prices of the EpiPen, Mylan’s signature product. The price increases have left many without access to epinephrine, vital for people with allergies going into anaphylactic shock. During the hearing, representatives voiced concerns that Mylan has control over the market as competitors have a hard time going past EpiPen’s patented design — so most offered alternatives, which relied on other types of auto-injectors, never got approved (you can be a pirate and make your own — but be warned if done incorrectly this may be fatal).

A small team of researchers including Mutasem Rawas-Qalaji, a pharmaceutical researcher at Nova Southeastern University in Florida, thinks they’ve found a way to solve this problem. They propose delivering the substance through a pill.

Working a bit like an ordinary orally disintegrating tablet (ODT), the treatment is designed to be administered under the tongue. That’s because delivering epinephrine through the stomach is pointless — the hormone breaks down before finding its way to the liver or blood. ODTs are meant to dissolve on the tongue and provide an alternative to liquid drugs or standard pills for patients who have trouble swallowing. They’re also used to bypass the digestive system altogether when delivering a drug. Rawas-Qalaji plans to have the pill dissolve in the blood-rich area of the under-tongue — so the epinephrine gets directly into the bloodstream.

He also spent the last few years tweaking the pill, making the epinephrine crystals it contains smaller and smaller to make sure that it will dissolve and be absorbed in seconds — there’s no time to wait during an anaphylactic shock. Still, it’s a much more inefficient way of doing things than just injecting the epi into muscle because a lot of the hormone gets lost in the mouth. While a pen holds roughly 0.3 mg of epi, the latest version of the tablet holds some 20 mg just to deliver an equivalent dose.

Dr. Mutasem Rawas-Qalaji and his epi tablets. Image credits Mutasem Rawas-Qalaji.

Dr. Mutasem Rawas-Qalaji and his epi tablets.
Image credits Mutasem Rawas-Qalaji.

But an EpiPen has flaws of its own apart from the cost, however. A Texas Uni study published last year found that only 16% of patients use the devices correctly. Most people don’t jam them with enough force into the leg or don’t hold it in place for the recommended ten seconds. They’re also bulky making them inconvenient to carry around, and they expire after about a year.

If approved, the tablets could solve a lot of EpiPen’s problems — it would be cheaper, simpler to use, smaller, more portable, and more stable. Rawas-Qalaji believes they could last up to seven years on shelf.

“So if you don’t use them you don’t have to go and buy another one,” he said.

As far as price is concerned, he couldn’t give an exact figure — it would depend on the manufacturer. He’s confident that the tablets can be sold “at a price that’s affordable and makes sense […] to fill a gap and meet the needs of the patients.”

Still a while to go

But there’s still a lot of work to be done before anyone’s putting these pills anywhere near their tongue.

“It’s a good idea. We’d love to have it. Patients would love to have it. There’s a lot of appeal,” says Robert Wood, an allergist at Johns Hopkins.

“But the risk of it not working is that people die.”

Wood says that the only way to make sure the pills work is to test them on people actually going through anaphylaxis — that means finding patients with severe allergies and asking them to expose to a potentially deadly allergen to test a drug that should work. Which, unsurprisingly, isn’t something that would fly with your average review board.

Rawas-Qalaji agrees that it isn’t ethical or feasible to do things that way, so he’s doing the best he can to make the pills as efficient as possible without endangering anyone. So far, he’s tested the tablet on rabbits. In the future, he plans to give the tab to healthy volunteers, then measure the epi concentration in their blood. If it’s equivalent to those from people given the EpiPen, the pills should work in stopping anaphylaxis. Wood also pointed out that the swollen mouth of a patient in shock might react differently to epinephrine than a healthy mouth.

“The swelling and other related unanswered questions have been discussed with FDA,” Rawas-Qalaji said for Popular Science.

“We had a good agreement of what can be tested and what [can]not.”

With input from the FDA, and help from specialists in allergies, Rawas-Qalaji and his team hope to start clinical trials sometime in the next few years. He also wants to get FDA approval for the tablets well before Mylan’s patents are up in 2025.

Mylan CEO Heather Bresch’s hearing on EpiPen was a complete disaster for the company

Heather Bresch, CEO of EpiPen producer Mylan, testified in front of the House Oversight and Government Reform Committee about the drug’s price increase on Wednesday.

Image via Youtube / wochit Business.

Image via Youtube.

The basic rundown of the EpiPen situation is that since 2007 when Mylan acquired patent rights for the device used to treat life-threatening allergic reactions, its price has increased by more than 500%. A two-pack of pens currently has a list price of 608$. Doug Throckmorton, deputy director of the FDA was asked to testify alongside Bresch as there is legitimate concern that lack of a competitor product on the market has allowed Mylan to inflate prices with commercial impunity.

Her prepared testimony released ahead of the hearing gave background on Mylan as a company and addressed some of the key points of the controversy. Congress, however, wasn’t impressed by her answers.

“Looking back, I wish we had better anticipated the magnitude and acceleration of the rising financial issues for a growing minority of patients who may have ended up paying the full [list] price or more,” her testimony reads. “We never intended this.”

The members of Congress had a lot of questions for Bresch, who testified alongside Doug Throckmorton, a deputy director of the Food and Drug Administration. In her defense, she said the company is implementing a number of programs to help patients pay for EpiPens.
[panel style=”panel-info” title=”Here’s the TL;DR version of what went down.” footer=””]

  • Bresch didn’t admit that the company raised EpiPens’ price to increase profits. She failed to present data pertaining to financial and patient assistance programs that Congress requested beforehand. She was unable to provide the info off the top of her head, either. She also said there were no plans to further increase prices in 2017, but didn’t give a definitive ‘no’.
  • Mylan’s EpiPen4Schools program also took a lot of flak — Rep. Tammy Duckworth called it a “monopoly” as schools that enrolled in the program had to sign a noncompete agreement. She was also outraged that most schools didn’t know the president of the National Association of the State Boards of Education, who was lobbying for them to join the program, was Bersch’s mother.
  • Congress also criticized Throckmorton as it felt the FDA’s convoluted approval process allowed this situation to arise. Throckmorton said FDA regulation prevented him from disclosing all the information the representatives requested about any applications for competitor products
  • By the end of the hearing, Bresch faced questions about Mylan’s tax inversions, private jets, and Rep. Earl Carter’s anger over Mylan’s generic version of the EpiPen.

[/panel]

Still here? Ok. Let’s go through the painful (for Bresch) step-by-step of the hearing.

*grabs popcorn*

It doesn’t make sense and we don’t believe you

“We’ve got a lot of questions,” said Rep. Jason Chaffetz, chairman of the committee, at the start of the hearing.

Chaffetz went on to ask how much money Mylan makes off each EpiPen and how much of that money goes towards its executives. He also pointed out that there’s an appalling lack of competition, which allowed for the price to skyrocket.  And when there are lives on the line, “parents don’t have a choice,” he added.

Rep. Elijah Cummings followed Chaffetz, saying he was “not impressed” by Bresch’s prepared testimony. He accused the company of using a “simple but corrupt business model” to cash in big, comparing them to Martin Shkreli of Turing Pharmaceuticals and the execs of Valeant Pharmaceuticals. He also put little faith in Mylan’s pledge to increase patient assistance programs. He referenced Shkreli’s testimony earlier this year, saying he “took his punches” then went back and kept on doing the same thing.

“We’ve heard that one before,” he said. “They never ever lower their prices.”

“I’m concerned this is a rope-a-dope strategy. It’s time for Congress to act.”

Bresch and Throckmorton both gave their prepared statements, which can be read here. Basically, it’s Bresch defending herself and Mylan while Throckmorton details how the FDA is putting effort into ramping up the approval of generics — exactly what you’d expect from a prepared speech.

The Q&A, however, was much more interesting.

Chaffetz asked what the company believed was going to happen when they raised the drug’s price. Bresch tried to explain that Mylan doesn’t actually make a lot of money on the drug.

“This doesn’t make any sense,” he said. “This is why we don’t believe you.”

He asked Throckmorton how many epinephrine products were in the FDA’s que right now, but to Chaffetz’s visible frustration he couldn’t answer the question. When pressed, Throckmorton said he wasn’t allowed to disclose “confidential commercial information” in that setting. Later, the FDA tweeted:

Another issue Chaffetz brought up was Bresch’s mother’s involvement in the issue. A USA Today article reported that she had used her influence as president of the National Association of State Boards of Education to support Mylan’s EpiPen4schools program. Bersch said the story distorted facts and basically shamed Mylan for giving schools free EpiPens.

Rep. Cummings wanted to calculate how much the company spends on marketing compared to what it rakes in. So he asked how much profit the company made off the sale of EpiPens in 2015. He was going by publicly available information but wanted the hard facts from the CEO. In the end, though, he had to figure it out without Bresch’s answers.

“You’re telling me you don’t know how much you spent on patient assistance programs and school-related programs in 2015?” he asked.

This does not look like a man happy about the answers he's hearing. Image via Youtube.

This does not look like a man happy with the answers he’s hearing.
Image via Youtube.

She replied they spent ‘maybe’ 105$ per pack because they had to raise awareness about anaphylaxis. Cummings then asked how much money was pooled into R&D in 2015 — he had to ask twice and went v-e-r-y slowly the second time. Again, Bresch came up short on answers.

“You knew what this hearing was about. I’m asking questions that if you’re the CEO I think that you would know,” he said.

Later, he asked if Bresch agreed that Mylan made hundreds of millions of dollars on EpiPen in 2015 alone, to which she replied that the pens weren’t all of the company’s $11 billion revenue. Cummings asked her again, to which she answered ‘yes’. She was then asked to produce documents showing the revenue on EpiPen (this were requested before the hearing but Bresch didn’t bring them along.)

Rep. Eleanor Norton then asked the question on everyone’s lips: will the price of EpiPen come down? The CEO replied that an authorized generic was the fastest way to make this happen — and, even if the branded product’s price went down, it wouldn’t necessarily make a difference on shelf price.

“What have you done to earn this 671% [compensation] increase?” Norton followed-up.

Bresch first tried to dodge the question by saying Mylan products have saved $180 billion in US expenses. Pressed by Norton, she pointed to the EpiPens Mylan has supplied to schools and in public places. Rep. Stephen Lynch asked how much the company made off of each pen, and Bresch tried to show using poster boards that the company got 235$ from each two-pack for a profit of about 50$. She added that the 300$ generic would make even less than 50$ profit for Mylan. Bresch later told Rep. Scott DesJarlais that she did not plan on increasing the price of the EpiPen in 2017. DesJarlais then asked if she thinks 600$ is too much to charge for the pens.

“We believe it was a fair price, and we’ve just now lowered that by half,” Bresch said.

But if the price was fair, why lower it at all, he asked Bresch. She replied it all came down to people paying closer to the list price, which wasn’t intended.

A mother’s touch

Duckworth raised concerns with the EpiPen4Schools program — to take part, the schools had to agree not to buy it from anyone else. Bresch replied that the schools are free not to join the program if they so wish.

“That, to me, is an unfair monopoly,” Duckworth said. “That’s right, they don’t have to buy them, but your own mother is out there […] passing out your guides for Mylan.”

She added that most schools had no idea the person lobbying for the program was connected to the CEO. Rep. Mick Mulvaney discussed government intervention in the project. He said that Congress talked about an industry it didn’t fully understand — but he made it clear that Bresch and Mylan won’t get off easily.

“I’ll tell you what we do know, though, is that you’ve been in our hallways to ask us to make people buy your stuff,” he said, citing that 11 states have laws requiring EpiPens be available in schools. “You’ve lobbied us to make the taxpayer buy your stuff. […] I was here when we did it.”

“You came and you asked the government to get in your business, so here we are today. And I was as uncomfortable with some of these questions as you were […] but I have to defend both my Republican and Democrat colleagues for these questions because you’ve asked for it, so I guess this is my message. If you want to come to Washington, if you want to come to the state capitol and lobby us to make us buy your stuff, this is what you get. You get a level of scrutiny and a level of treatment that would ordinarily curl my hair, but you asked for it!”

Rep. Earl Carter discussed the issue of pharmacy benefits managers, companies that serve as middlemen in negotiating the price of drugs. He’s been investigating this type of companies as he believes they’re part of the reason why patients are paying more and more for prescription drugs. Bresch agreed that more transparency is needed in this regard. Talking on the subject she also brought up the company’s authorized generic, which didn’t go over well.

“You know I know better than that,” Carter said. “Don’t try to convince me that you’re doing us a favor.”

He said that if Mylan had reduced the price of their EpiPens in the first place, they wouldn’t have received rebates from PBMs. Carter requested Bresch to follow up with more details about Mylan-PBM contracts.

Rep. Bonnie Watson Coleman then asked how Bresch came to the hearing, to which she replied she had flown in from Pittsburgh where Mylan’s US corporate offices are based on a private jet. Coleman then asked about the company’s tax rates. Last year, Mylan moved their headquarters to the Netherlands and has since had a 15-17% tax rate, down from roughly 20-25% the year before — this, Coleman points out, means the company pays less on their taxes than the average American. During the discussion, Bresch said that the company is “physically” run out of their Pennsylvania offices, where the execs are based.

“This is a sham and a shell, and it’s really sad to hear this,” Coleman said.

Chaffetz also discussed the EpiPen’s classification under Medicaid as a “Non-Innovator Multiple Source Drug.” Bresch said that the status was decided before the company acquired the patent.

By the end of the hearing things weren’t looking very well for Bresch.

“If I could sum up this hearing, it would be that the numbers don’t add up,” Cummings said. “It is extremely difficult to believe that you’re making only $50 when you’ve just increased the price by more than $100.”

“It just feels like you’re not being honest with us,” he added, saying some of the numbers and charts Bresch used during the hearing seemed over-simplified.

It seems that the representatives took previous dealings with Turing and Valeant Pharmaceuticals to heart with Cummings saying that Mylan’s arguments sounded a lot like what they’ve heard before. Bresch and Throckmorton have been given 10 days to provide the committee documents to answer some of the points that weren’t satisfactorily answered during the hearing.

You can watch the full hearing here:

https://www.youtube.com/watch?v=f60bxayNYpg