The drugs don’t work against every cancer — but on rare occasions, they work miracles. Now some doctors are offering immunotherapy to dying patients.
As the United States Surgeon General, it is my sworn duty to protect and improve the health of the American people. Right now, we are in the middle of an opioid epidemic that claims 115 lives each day. Naloxone gives us the ability to #savealife #getnaloxone
A growing percentage of medical devices and drugs used in American operating rooms are made in China, and many of them are on the White House’s list.
The story of Slater’s attempts to get and stay well weaves throughout “Blue Dreams: The Science and the Story of the Drugs That Changed Our Minds” and provides some of the book’s most poignant and lyrical writing. Just as important, her experience makes her a convincing travel guide into the history, creation and future of psychotropics. She is, understandably, not an uncritical cheerleader. But she resists the facile role of hard-charging prosecutor. And no wonder, really, given that the drugs have allowed her to have two children, write nine books, marry (and divorce) and hold dear friendships.
Credit Alessandra Montalto/The New York Times
So, when she takes us back to the 1950s and the story of Thorazine, she doesn’t just give us a “One Flew Over the Cuckoo’s Nest” bag of horrors, but also a glimpse into doctors’ excitement when the drug quelled patients’ delusions and hallucinations and the once-comatose resumed living. A former barber, who had been in a haze for years and for whom all previous treatments failed, returned to shaving (his first customer: the doctor who gave him Thorazine). A juggler asked for billiard balls and began juggling again. And people on one psychiatric ward picked up musical instruments, used drills and saws, held conversations that had been unthinkable shortly before.
In what becomes a through-line in the book, no one fully understood how the drug worked (nor do we know what happened to the juggler or barber once they left the asylum). It was simply enough that it seemed to be working. And yet, in high doses and over the long term, patients often experienced tardive dyskinesia, which includes tongue thrusting, lip smacking, restlessness, involuntary movements of arms and legs, which become twisted like pretzels. When Slater wonders aloud to a psychiatrist why the new class of antipsychotics is really so much better than the old ones, he says: “You have to pick your poisons. Which would you rather be in two years — a circus freak or a diabetic?”
She takes us on similar journeys into lithium and MAO inhibitors, each bringing hope and problems. And then, in the late 1980s there’s the arrival of serotonin reuptake inhibitors, known as SSRIs, and their promise to be different from the antidepressants of the past. The standard explanation is that Prozac, Celexa, Zoloft and other SSRIs boost serotonin levels. But studies have never proved that depressed people suffer from low serotonin (some do, some have normal levels and others have high levels). And SSRIs often fare no better than placebos for mild to moderate depression. Still, doctors tend to talk about depression as if the science is settled, often telling patients: If you’re diabetic you take insulin; if you’re depressed you take a pill. The analogy, of course, doesn’t hold. There is no blood test, no X-ray, no urinalysis that pinpoints depression. It is a field, Slater writes, “still stuttering, with at best a slippery grasp on the science behind its pills and potions, a legion of medical men and women who can help you in one way but hurt you in another.”
Hope does arrive in the second half of “Blue Dreams,” when Slater walks us through emerging interventions. Unfortunately, by this point she’s taken us through so much material and still has so far to go — including brain stimulation and memory drugs — that the journey begins to feel too wide-ranging and, occasionally, too thin on details about what we’re passing along the way.
Still, several of the up-and-coming treatments — many of them not new at all — shift our focus from unmediated pill popping. Among them are placebos, which don’t work for all patients and have no effect on those with Alzheimer’s. But, as Slater rightly notes, numerous studies show their amazing potency, which remains too untapped by a psychiatry field still enthralled with drugs.
Like placebos, hallucinogens also aren’t new, of course, but researchers are repurposing them in promising ways. Studies show that psilocybin, the active ingredient in so-called magic mushrooms, curbs smoking addiction, as well as relieves anxiety and depression for people with end-stage cancer. And in clinical trials, psychotherapy combined with MDMA (the chemical more commonly known as ecstasy) offers significant relief for PTSD sufferers. The drug, which creates feelings of empathy and euphoria, allows traumatized victims to recall their terrors in a calm state of mind and establish deep trust with their therapists — ingredients that pave the way for psychological change.
One of the keys for MDMA, psilocybin and some placebo therapies is the connection between patient and provider. And connection is exactly what vanishes during Slater’s own depressive states. Her primary feeling, she writes, is “the loss of love — my people falling away — and the loss of language, my words dwindling so low that my thought seems to move without rhythm or reason.”
It’s no surprise that Slater goes searching for relief among these new treatments. She tracks down a therapist who uses MDMA in her practice. And in the cozy office painted in calming colors, Slater tells the therapist her history and lists her prescriptions. MDMA won’t work for Slater, the therapist tells her; her current medications would block the drug’s effects. Slater knows from past experiences that she can’t risk weening herself from the prescriptions that keep her stable. Her dependency on our terribly imperfect drugs has ruled out her candidacy for more promising ones.
Attorney General Jeff Sessions said he would use legal actions and task forces to crack down on prescription opioid manufacturers, distributors and prescribers.
Alex M. Azar II, the new secretary of health and human services, who was a top executive at the drugmaker Eli Lilly for nearly 10 years, echoed that concern. “That shouldn’t be happening,” he said.
Pharmacy benefit managers say they hold down costs for consumers by negotiating prices with drug manufacturers and retail drugstores, but their practices have come under intense scrutiny.
The White House Council of Economic Advisers said in a report this month that large pharmacy benefit managers “exercise undue market power” and generate “outsized profits for themselves.”
Steven F. Moore, whose family owns Condo Pharmacy in Plattsburgh, N.Y., said the restrictions on pharmacists’ ability to discuss prices with patients were “incredibly frustrating.”
Mr. Moore offered this example of how the pricing works: A consumer filling a prescription for a drug to treat diabetes or high blood pressure may owe $20 if he uses insurance coverage. By contrast, a consumer paying cash might have to pay $8 to $15.
Mark Merritt, the president and chief executive of the Pharmaceutical Care Management Association, which represents benefit managers, said he agreed that consumers should pay the lower amount.
As for the use of gag clauses, he said: “It’s not condoned by the industry. We don’t defend it. It has occurred on rare occasions, but it’s an outlier practice that we oppose.”
However, Thomas E. Menighan, the chief executive of the American Pharmacists Association, said that such clauses were “not an outlier,” but instead a relatively common practice. Under many contracts, he said, “the pharmacist cannot volunteer the fact that a medicine is less expensive if you pay the cash price and we don’t run it through your health plan.”
A bipartisan measure that took effect in Connecticut this year prohibits the gag clauses. It was introduced by the top Democrat in the Connecticut Senate, Martin M. Looney, and the top Republican, Len Fasano.
“This is information that consumers should have,” Mr. Looney said in an interview, “but that they were denied under the somewhat arbitrary and capricious contracts that pharmacists were required to abide by.”
Mr. Fasano said that consumers were sometimes paying three or four times as much when they used their insurance as they would have paid without it. “That’s price gouging,” he said in an interview.
The legislation, Mr. Fasano said, encountered “a lot of resistance” from large pharmacy benefit managers and some insurance companies.
In North Carolina, a new law says that pharmacists “shall have the right” to provide insured customers with information about their insurance co-payments and less costly alternatives.
A new Georgia law says that a pharmacist may not be penalized for disclosing such information to a customer. Maine has adopted a similar law.
In North Dakota, a new law explicitly bans gag orders. It says that a pharmacy or pharmacist may provide information that “may include the cost and clinical efficacy of a more affordable alternative drug if one is available.”
The North Dakota law also says that a pharmacy benefit manager or insurer may not charge a co-payment that exceeds the actual cost of a medication.
The lobby for drug benefit companies, the Pharmaceutical Care Management Association, has filed suit in federal court to block the North Dakota law, saying it imposes “onerous new restrictions on pharmacy benefit managers.”
Specifically, it says, the North Dakota law could require the disclosure of “proprietary trade secrets,” including information about how drug prices are set. “P.B.M.–pharmacy contracts typically preclude a pharmacy from disclosing to the patient the amount of a reimbursement,” the lawsuit says.
Gov. Asa Hutchinson of Arkansas, a Republican, said this past week that he would call a special session of the State Legislature to authorize the regulation of pharmacy benefit managers by the state’s Insurance Department.
He said he feared that some independent pharmacists receiving “inadequate reimbursement” from the benefit managers might go out of business, reducing patients’ access to care, especially in rural areas.
Despite efforts by the Food and Drug Administration to encourage more competition for drugs that have no generic alternatives, companies like Teva will still charge as much as the market will bear as long as there is no significant competition. And even companies that come under intense criticism, like Valeant, can often neutralize consumer upset through assistance programs.
While those can lower out-of-pocket costs for patients, the programs stick insurers with the bulk of the bill, which in turn can be passed on to consumers through higher premiums and deductibles.
Jay Copeland, 59, has been taking Syprine for a decade to treat Wilson disease, a condition that causes copper to build up in the body, leading to organ and neurological damage if not treated.
Calling the generic price “incredibly punitive,” Mr. Copeland said his employer’s insurance shields him from most of the drug’s cost, but he worries what would happen if he were to lose his job. Teva’s slightly lower price, he said, “would make relatively little difference to me if I were put in the position to pay enormous out-of-pocket costs.”
To encourage more generic competition, the F.D.A. recently published a list of off-patent drugs that have no competition and cleared a backlog of generic applications. But as the Syprine case shows, it often isn’t as simple as adding a single generic competitor.
“By and large, generics work when there are multiple players,” said David Maris, an analyst at Wells Fargo who wrote this week about Teva’s generic Syprine price. “When there’s not, you get this.”
If there are just a few players and if the drug treats a small group of patients, as is the case with Wilson disease, the companies will try to make as much profit as they can. Just 5,226 prescriptions were filled for Syprine, also known as trientine hydrochloride, in the first three quarters of 2017, according to the data research firm IQVIA.
Wilson disease is believed to affect between 8,000 and 10,000 people in the United States, and some with the condition take other drugs, according to Mary Graper, the vice president of scientific affairs at the Wilson Disease Association, a patient group.
“Generic companies are for-profit companies, too, and so it’s not surprising to me that they price the product at what they think the market will bear,” said Dr. Aaron S. Kesselheim, an associate professor at Harvard Medical School who has studied drug prices.
Credit Drew Angerer for The New York Times
A spokeswoman for Teva declined to comment on how it set its price, but said the company considers a range of factors. “If there is more competition and ample supply, pricing will continue to fall,” said the spokeswoman, Kaelan Hollon.
Teva, which calls itself the world’s leading manufacturer of generic drugs, has struggled in recent years with management turmoil, lost sales of a leading brand-name drug, and — in a twist — with the falling prices of many commonly used generic drugs. In December, it announced a major reshaping, including cutting 25 percent of its work force.
Patients with Wilson disease had been watching for the arrival of a generic Syprine, but Teva’s announcement took them by surprise, Ms. Graper said. «We had no idea what to expect, but I had personally hoped for more of a discount.”
Not to be outdone, Valeant followed Teva’s move with the release of its own “authorized” generic of Syprine. It’s a common tactic by brand-name drugmakers who want to compete directly with generic manufacturers without lowering the price of their brand-name product, which some patients continue to prefer. Valeant’s authorized generic sells for $19,119, according to Elsevier.
Lainie Keller, a spokeswoman for Valeant, said the list price for its generic did not reflect discounts the company negotiates with buyers, although she would not disclose those discounts.
She said Valeant’s patient assistance programs have recently been improved to ensure that privately insured patients only pay about $5 a month. Those without insurance can get the medication for free if they meet certain income requirements.
Valeant was once a Wall Street favorite that kept investors happy by buying up old, off-patent drugs like Syprine, sharply raising their prices, and investing little in research and development. That changed in 2015, when questions were raised about the impact this strategy was having on patients, and about the company’s financial practices and its ties to a mail-order pharmacy.
Congressional and federal investigations into the company’s practices followed, leading to a plummeting stock and the departure of the chief executive and major investors.
Ms. Graper, whose group accepts donations from Valeant and Teva, confirmed that Valeant’s patient assistance program has improved since members of her group testified before the Senate about how the company’s price increases led them to stop taking their drugs.
Such industry assistance programs have themselves come under scrutiny — including ones run by Valeant — because they have helped make high drug prices more palatable, easing patients’ out-of-pocket burdens while leaving insurers to pay the rest.
Ms. Graper expressed hope that if other generic competitors enter the market, the price will continue to fall. “I think we have to wait and see where these two land,” she said.
She and others said they were frustrated that despite a flurry of Congressional hearings, government investigations and promises by politicians, the price of many of the drugs that stoked the initial outrage remain as high as ever.
In addition to Syprine, Daraprim, an old drug used to treat a serious parasitic infection, is still $750 a pill more than two years after Mr. Shkreli became a social media villain for his role in raising the price overnight from $13.50.
The cost of the EpiPen is an exception to the trend. In response to the outcry over the EpiPen’s price, which reached about $600 at its height for a pack of two, Mylan came out with a cheaper, authorized generic. A pack of EpiPens can now be bought for about $300 at many pharmacies.
“I had hoped that something would come of it, that the politicians would take some action, but obviously not much has happened,” Mr. Copeland said. “It’s all disheartening.”
“This really looks to be a breakthrough in vaccinating older adults,” agreed Dr. Jeffrey Cohen, a physician and researcher at the National Institutes of Health.
What’s causing the enthusiasm: Shingrix, which the pharmaceutical firm GlaxoSmithKline intends to begin shipping this month. Large international trials have shown that the vaccine prevents more than 90 percent of shingles cases, even at older ages.
The currently available shingles vaccine, called Zostavax, only prevents about half of shingles cases in those over age 60 and has demonstrated far less effectiveness among elderly patients.
Yet those are the people most at risk for this blistering disease, with its often intense pain, its threat to vision and the associated nerve pain that sometimes last months, even years, after the initial rash fades.
Almost all older Americans harbor the varicella zoster virus that causes shingles; they acquired it with childhood chickenpox, whether they knew they had the disease or not.
The virus stays dormant until, for unknown reasons, it erupts decades later. The risk rises sharply after age 50.
Shingles is hardly a minor menace. “A million cases occur in the United States each and every year,” Dr. Schaffner said. “If you’re fortunate enough to reach your 80th birthday, you stand a one-in-three to one-in-two chance of shingles.”
Preventing the great majority of these cases — along with the risk of lingering and debilitating nerve pain, called postherpetic neuralgia — would represent a major advance in public health.
So while the old vaccine will remain on the market, the C.D.C. committee voted to make Shingrix the preferred vaccine and recommended it for all adults over age 50 — a group younger by a decade than those earlier encouraged to get Zostavax.
The committee also recommended Shingrix for adults who’ve previously gotten Zostavax, since a smaller study in people over age 65 demonstrated effectiveness and safety in those already vaccinated. The Food and Drug Administration approved Shingrix last month.
Once the C.D.C.’s director endorses the committee’s recommendations, and the agency publishes them, insurers — including Medicare and Medicaid — will start covering the vaccine.
“By early 2018, it should be broadly available to consumers in the U.S.,” said Dr. Thomas Breuer, chief medical officer of GSK Vaccines. (Canada has also approved Shingrix; it awaits approval in Australia, Japan and Europe.)
What makes the new vaccine so promising, especially for older adults?
* It provides better protection against shingles from the start. Though Zostavax, introduced in 2006, can reduce shingles cases by about half (and postherpetic neuralgia by two-thirds), that overall rate conceals big differences by age.
That vaccine’s effectiveness drops from 64 percent for people in their 60s to 38 percent among those over age 70, and falls still lower for people in their 80s.
But the new vaccine protects nearly as well in older groups as in the middle-aged. Shingrix racked up a 97 percent effectiveness rate in adults over age 50 and, in a separate study of people over age 70, prevented 90 percent of shingles in those 70 to well past age 80.
“In groups such as the elderly, who often don’t maintain vigorous responses to vaccines, this represents extremely strong disease protection,” said Dr. Kathleen Dooling, an epidemiologist at the C.D.C.
* Shingrix’s protection appears to last longer. Among seniors, the effectiveness of Zostavax wanes with disappointing speed. “After 11 years, the protection was close to zero,” Dr. Harpaz said.
Regulators don’t yet have 11 years of data on Shingrix, but in some samples, it remained effective for six years or longer, according to GSK. That should greatly reduce the incidence of postherpetic neuralgia, too, assuming the 42 million people in their 50s start getting vaccinated.
* The new vaccine may protect people with compromised immune systems.
A substantial number of older Americans have suppressed immunity because they’re undergoing chemotherapy or transplants, have H.I.V. or take steroids. For them, the previous vaccine was off-limits because it was made with a weakened live virus.
Yet immune suppression itself leaves the people vulnerable to shingles. Shingrix, a recombinant vaccine made from a glycoprotein and a combination of immunity boosters called adjuvants, doesn’t pose the same danger.
The C.D.C. committee held off on recommending Shingrix for the immunocompromised, because GSK is still running trials with these patients. But since the F.D.A. did not declare Shingrix contraindicated for them when approving it, they can get the vaccine once it’s available.
Public health advocates do foresee a couple of potential problems.
First, Shingrix requires two doses, administered at least two months apart. Prodding the older population to get a single shot has proved tough: barely 31 percent of those over age 60 have been vaccinated against shingles. How much harder will it be to persuade people to get two Shingrix injections?
Further, “it tends to be a bit of an ouch-y vaccine,” Dr. Schaffner cautioned.
In studies, most older recipients said they’d experienced pain, redness or swelling in their upper arms for a day or two after the shot, and 8.5 percent of those over age 70 deemed those symptoms uncomfortable enough to interfere with normal activities.
About half of those over age 70 reported more systemic side effects like fatigue, fever or aching joints, lasting one to two days. Physicians and pharmacists should prepare people for such reactions, Dr. Schaffner said.
“If people anticipate it, they’ll cope with it better. They’ll take a couple of Tylenol” — and not worry that something is seriously wrong.
They may feel pocketbook pain, too. Zostavax is the most expensive adult vaccine, and at $140 for each dose (plus the cost of administering the injection), Shingrix will be pricier still.
The 50- to 65-year-old cohort, many of whom have coverage under employee health plans, may not find that much of a barrier. At older ages, cost matters more.
Medicare will cover Shingrix under Part D (like its predecessor), not under Part B like the flu vaccine. That complicates reimbursement for those seeking vaccination in doctors’ offices, so Medicare patients will probably find it simpler to head for a pharmacy.
But not all Medicare recipients have Part D, and those that do could face co-payments.
Still, it’s no contest: The hazards of shingles and its complications dwarf any problems yet reported with Shingrix.
“Compared to shingles, a little arm pain for a day or so is a small price to pay,” Dr. Schaffner said. “If you know people who’ve had this illness, you’ll be first in line for this vaccine.”
An Amazon spokeswoman, Lori Torgerson, refused to comment on “rumors or speculation” about Amazon entering the pharmacy business, but she shared a statement that suggested other motivations for the paperwork. “Wholesale licenses are required for Amazon Business to sell professional-use only medical devices in certain states,” she said.
There is little doubt, though, that Amazon is interested in at least some aspects of the pharmacy business. Brittain Ladd, a supply chain consultant who worked at Amazon until earlier this year on groceries and other initiatives, said he participated in discussions about how Amazon could enter the category, including through acquisitions.
“The pharmacy business was always a topic of interest when I was with Amazon, and there was a sincere desire on the part of Amazon to create a better customer experience across pharmacy and health care as a whole,” he said.
While Mr. Ladd said he isn’t privy to the company’s current strategy, he believes existing pharmacy companies are right to be worried. “My advice is that executives at pharmaceutical companies should crush all assumptions when it comes to Amazon and their ability to enter, innovate and reimagine the pharmacy business and health care,” he said.
If Amazon decides to enter the market, it could take a variety of avenues, analysts said.
The easiest way in would be to set up a mail-order pharmacy that focused on price-sensitive customers without health insurance or who have high-deductible plans that require them to pay for some drug costs upfront. To do this, Amazon would need retail pharmacy licenses in every state — a hurdle, certainly, but not an insurmountable one, the analysts said.
The company’s $13.4 billion deal for Whole Foods is the latest signal of Amazon’s ambitions to have a hold on nearly every facet our lives — like the computer servers that power our favorite websites and the food we eat.
“They can at least dip their toe in the water with the cash-pay customers, and learn the business,” said Ana Gupte, an analyst for Leerink Partners.
She said cash-paying customers account for 5 percent to 10 percent of the $560 billion prescription drug business.
The idea could prove attractive to customers who already go to Amazon for a wide range of shopping items, from shoes to electronics to diapers. Retailers like Target and Walmart have added pharmacies to bring in extra business for a similar reason. Amazon’s recent acquisition of Whole Foods could also provide a physical location for pharmacies.
“A large part of the infrastructure is already there,” said David Maris, an analyst for Wells Fargo.
In a call with analysts this week, Timothy C. Wentworth, the chief executive of the pharmacy-benefit manager Express Scripts, indicated a willingness to work with Amazon to reach these cash-paying customers. “We certainly see that as something where if they wanted to move into a space, we could be a very natural collaborator,” he said.
If Amazon wanted to go bigger, Ms. Gupte and others said, it could sell to insured customers and even serve as a pharmacy-benefit manager, overseeing drug coverage for people on behalf of insurers and large employers.
This would be far more complex. It would likely require Amazon to either acquire a pharmacy-benefit manager or enter into a partnership with an existing one. Expanding the pharmacy business without the aid of a major pharmacy-benefit manager would be tough, because the benefit managers serve as gatekeepers to insured patients, deciding which pharmacies they can and cannot use. The benefit managers also operate their own mail-order pharmacies, which might make them less willing to accommodate Amazon.
Some said they expect that if Amazon chooses to enter the health care business, it would do so in a big way. The company could attempt to provide comprehensive services to patients, doctors and others, far beyond selling drugs.
Nadina J. Rosier, the health and group benefits pharmacy practice leader at Willis Towers Watson, said other areas the company could explore include offering virtual doctor consults, or using the Amazon Echo, its voice-controlled smart device, for health care applications.
No matter the short-term steps Amazon is taking, Ms. Rosier said, her research has demonstrated that it is “clearly looking to revolutionize how health care is delivered in some way.”
But while Amazon has a track record for upending major industries, from books to groceries, she said health care is complicated and there would be intense pressure to get it right. “It is just a sensitive topic,” she said. “We don’t have as much scrutiny of how much you paid for your jeans, or your shoes.”