Humira: the biggest moneymaker

Humira, a drug produced by AbbVie, is the most lucrative franchise in pharmaceutical history and the top-selling pharmaceutical in the world, generating an annual revenue of $20.7 billion. It’s an anti-inflammatory drug used for autoimmune, rheumatologic, and gastrointestinal diseases. 

Since its approval in 2002, the price has increased about 30 times. By the end of 2016, the list price had gone up 60 percent to over $80,00 a year. One company that directly covers its employees' health claims found that Humira was costing the company well over $70,000 a year for one employee. (In 2020, Medicare covered the cost of Humira for 42,000 patients.)

AbbVie has been able to ward off competitors by employing patent-prolonging strategies, such as filing multiple additional patents on the same drug. For example, they obtained a patent on the autoinjector device and a separate patent for the “firing button.” They also obtained patents on production methods and dosing regimens. (Most, if not all, drug companies employ such methods. In fact, 78 percent of recent new patents were for existing drugs.) In all, a total of 247 patent applications for Humira have been filed in the United States.

Competitors, such as Amgen’s Amjevita, have finally entered the market by developing biosimilar drugs—drugs that are very close in structure and function to a medicine but not an exact copy. In this way they were able to invalidate AbbVie’s Humira patents, enabling them to enter the U.S. market before the technical end of Humira’s monopoly period, which in the United States was 2039.

It will be interesting to see what happens pricewise. A spokeswoman for Amgen said, “We price our products according to the value they deliver.” Huh?

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A myopia epidemic

Myopia (nearsightedness) has reached epidemic proportions worldwide. By 2050, according to one estimate, half the world’s population will be nearsighted. In the U.S., its prevalence has jumped from 25 percent in the 1970s to 42 percent in the early 2000s.

People with myopia can see an object up close clearly, but at a distance the object is blurred. That’s because, instead of the focus of light landing on the retina, it occurs in front of the retina.

Myopia predisposes people to other eye conditions that can lead to blindness. Higher degrees of myopia are associated with premature cataracts, glaucoma, retinal tears and detachments, and myopic macular degeneration.

Researchers believe the myopia epidemic is the result of children not getting as much outdoor play as in the past. Being outdoors is important because outdoor light enables the visual system to process a variety of light wavelengths and intensities—variety that’s needed for normal eye development and growth. (Studies could not support unequivocal evidence that using digital devices is causing the shift toward myopia.)

In the U.S., myopia hasn’t garnered the same sense of urgency and funding as is the case in other parts of the world. Because we in the U.S. don’t have a nationalized health system, we also don’t have a national database to provide standardized tracking and reporting that would provide good prevalence data for myopia. To attract attention and funding for effective screening, treatment, prevention, and research, experts believe that myopia needs to be recognized as a disease.  

I don’t know whether I’m nearsighted or farsighted. I don’t normally wear glasses. I have a pair for reading, and another pair for distance, which I rarely use, even though they work well. As with most old people, as a child, I spent more time outdoors than kids do nowadays.

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Antidepressants

During the Covid epidemic, rates of depression and anxiety soared, and many Americans turned to antidepressants to help them cope. Even before Covid, one in eight American adults was taking an antidepressant drug. Zoloft is now the 12^th most prescribed medication in the U.S. (Other examples of antidepressants include Lexapro, Effexor, Celexa, and Prozac.) Eighty percent of antidepressants are prescribed by primary care doctors who have not had extensive training in managing mental illness.

Researchers question how well they work. Some even say they’re barely better than a placebo.  Psychiatrists who prescribe them believe they do help most people who take them. They’re most effective in helping moderate, severe and chronic depression, but they don’t tend to help mild depression. In fact, they don’t work for about a third of the people who take them.

Use of antidepressants assumes the “chemical imbalance” theory of depression: low levels of neurotransmitters in the brain. The most prescribed antidepressants are selective serotonin reuptake inhibitors (S.S.R.I.s), which prevent neurons from sucking up the neurotransmitter serotonin, allowing more of the chemical to float around in the brain. Other antidepressants also increase circulating levels of other brain chemicals, such as dopamine.

Research has shown that people with depression consistently have less volume in an area of the brain called the hippocampus that’s important for regulating mood. The current prevailing theory is that chronic stress can cause the loss of connections (synapses) between cells in the hippocampus and other parts of the brain, potentially leading to depression. Antidepressants are now thought to work at least in part by helping the brain form new connections between cells.

Because I’ve been lucky at never suffering from depression, I was curious about the genetic component. When I went to 23andMe to see about that, I got a notice that said “Discover your genetic likelihood of developing this condition” which I could get by subscribing to their “Premium” package. Maddening. No wonder the company is in trouble.

For an introduction to this blog, see I Just Say No; for a list of blog topics, click the Topics tab.

Thalidomide in the U.S.

If you’re old enough, you should remember the epidemic of babies born in the 1960s—mostly in European countries—with shortened limbs and other serious medical conditions.

A German drug company had developed a new non-addictive sedative—a supposedly safe wonder drug. It was the second-best seller in Germany, right behind Aspirin. Active ingredient: thalidomide. People used it to get a good night’s sleep. For pregnant women, it helped with morning sickness. Because the drug was such a big moneymaker in Germany, Merrell, a U.S. drug manufacturer, got a license to make and sell it in the U.S.

On September 8, 1960, Merrell submitted the drug application to the FDA for approval. Because it was already so popular in Europe, Merrell thought it would be a shoo-in for approval. Just let the new girl rubber stamp it. The “new girl” was Frances Kelsey, an MD with a PhD in pharmacology who had joined the FDA a month before the application was submitted. She was in charge of reviewing the clinical trials portion of the application, which was the size of four phone books bound together.

Kelsey had 60 days from the date of submission to respond to the application. If she did not, the drug would automatically be put on the market. To deny it, she had to prove it was unsafe. She was disturbed by the lack of details about the clinical trials, such as the participants’ age, sex, dosages, how long they were on the drug, adverse effects, and so forth. The company had never performed randomized, placebo-controlled studies over a sufficient period of time. In order to reject the application, Kelsey needed data proving the drug wasn’t safe—data she didn’t have.

Fortunately, there’s a loophole allowing reviewers to delay action by calling the application incomplete. You can just ask for more information and stall, which Kelsey did. In the meantime, Merrell was ready to go ahead. Even without approval, Merrell was already distributing the drug to thousands of patients across the U.S. They’d sent millions of thalidomide pills to doctors in so-called clinical trials. They’d already had brochures printed and enough raw material to make 15 million pills. They’d also lined up dozens of sales representatives to start hawking the drug in hospitals.

Kelsey kept stalling. The old-boy network was furious. In November 1961, the shit hit the fan. A doctor in Scotland, as well as other sleuths in Europe, had found a side effect of thalidomide, which was reported in a letter in The British Medical Journal. It turns out that the drug is safe in late pregnancy but harms an early embryo by blocking the development of blood vessels.

Thalidomide had been on the market for four years at this point. Thousands of babies had been affected. In the U.S., the official FDA count was 17 affected babies, nine of them born to mothers who took the samples; eight who had obtained the drug in other countries. But approximately 150 others in the U.S. have self-identified as thalidomide survivors. Absent Kelsey, it could have been much worse.

The scandal led to the Kefauver Harris Amendments of 1962, which required manufacturers to provide data from animal experiments and human trials to prove that a drug is safe before it can be sold. Ya think?

For an introduction to this blog, see I Just Say No; for a list of blog topics, click the Topics tab.