When Andrew Archuleta’s bladder cancer returned two years ago, his doctor prescribed periodic treatments of a powerful immunotherapy designed to stave off another recurrence. But the latest round, scheduled for May, was abruptly canceled because of a severe shortage of the drug.

“I keep calling the clinic and saying, ‘Is my treatment still canceled?’ and they say, ‘Yes,’ ” said the 65-year-old Colorado resident. Now he fears the cancer might come back in an even more aggressive form, endangering his bladder — or even his life, if the disease were to spread. With his anxiety and blood pressure rising, he temporarily took Prozac.

“My doctor says he feels really bad about it, but I keep wondering: How could this happen in this day and age?” he said.

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Archuleta is one of tens of thousands of people across the country affected by a shortage of the gold-standard treatment, called BCG, for early-stage bladder cancer, with potentially life-changing consequences.

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BCG, a decades-old bacterial concoction, is the newest poster child for increasing drug shortages, a problem that seems to defy solution. Some shortages are caused by production missteps, quality problems and even natural disasters, such as the 2017 hurricane that hit Puerto Rico. But others, especially some involving older, hard-to-make drugs, experts say, can result from slim profits and industry consolidation.

At a time of intense focus on escalating drug prices, BCG shows an unexpected flip side: Prices can be too low to spur companies to produce urgently needed medications.

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BCG’s price, which runs about $150 or so a dose, is “too low,” said Benjamin Davies, a urologist at the University of Pittsburgh Medical Center who says he is politically left of center and a frequent critic of high drug prices. He said Merck, the only supplier of the single BCG strain approved in the United States, should raise its price significantly to make the therapy more profitable and attract potential competitors.

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Merck has raised the price of the off-patent drug modestly in recent years but has shown little interest in a big hike, perhaps fearing a backlash. After former pharmaceutical executive Martin Shkreli was widely condemned for jacking up the price of an old HIV drug, “manufacturers are sensitive to charges of gouging,” said Rena Conti, a health-care economist at Boston University.

Mike Nally, Merck’s chief marketing officer, said the company isn’t looking to make a big profit on BCG, which is grown on potatoes in a facility in North Carolina. The plant, which has tripled production over the past seven years, is at maximum capacity and any further increase could take years.

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With global demand for BCG rising, it would be “healthy” if there were other suppliers, he acknowledged. Lack of industry interest suggests “there’s an element of market failure here.”

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That failure now threatens patients. Because of the BCG shortage, some patients “are being undertreated, and some are going to have to undergo radical surgery and lose their bladders,” said Bernard Bochner, a urologist at Memorial Sloan Kettering Cancer Center. Those patients will have to wear a urine-collection bag or undergo difficult surgery to make a new bladder out of their intestines — life-altering changes, he said.

Fearful of such an outcome, patients are calling hospitals and clinics and scouring chat rooms looking for help. “We are hearing from more and more desperate patients every day,” said Stephanie Chisolm, director of education and research at the Bladder Cancer Advocacy Network, a patient group.

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BCG, which is used for bladder cancer that has not invaded the muscle wall, helps prevent the disease from coming back or getting worse. If cancer enters the muscle, the bladder often is removed. If it spreads to other organs, it can be deadly.

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Deborah Norris said her father, Cecil Northrup, 83, was diagnosed in 2010 with bladder cancer that returned in 2013 and again earlier this year. He got three years of BCG as “maintenance” treatment after the first time the cancer returned, but none after the second time. That makes the chance of another recurrence much higher, his doctor told him.

Critical shortages of an array of therapies, including pediatric cancer drugs, painkillers, psychiatric medications, sodium bicarbonate and IV solutions, have occurred on and off for years. The number of new drug shortages rose to 186 last year, the highest number since 2012, said Erin Fox, senior pharmacy director of the University of Utah’s Drug Information Service. Ongoing shortages have exceeded 200 for the past several years.

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The Food and Drug Administration defines shortages differently, but said in a presentation last fall that shortages have become more prevalent in the past year and are lasting longer — sometimes more than eight years for a single drug.

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Hospital pharmacists often juggle supplies to keep treatments on track. But sometimes patients are harmed by shortages. During a cancer-drug shortage, young lymphoma patients who got a substitute treatment relapsed at higher rates and required more chemotherapy, which is linked to heart disease, infertility and malignancies later on, a 2012 study found.

Shortages of “supportive care” drugs — for chemotherapy-induced nausea or to protect the kidneys — can delay cancer treatments, said Yoram Unguru, a pediatric oncologist at Children’s Hospital at Sinai in Baltimore. When he gets the hospital’s list of shortages, “I scream, I shout, I shake my head,” he said.

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Many of the most severe shortages affect generic, sterile medications that are injected or infused in hospitals or in outpatient clinics and doctors’ offices. Often, those drugs are complex and require special equipment to make. Hospitals push for the lowest possible prices because they receive lump sum payments by Medicare based on patients’ diagnoses, said Fox.

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In some cases, reimbursements should be increased, said former FDA commissioner Scott Gottlieb. “You want to have a reimbursement scheme with healthier [profit] margins” to encourage firms to stay in the market and invest in manufacturing, he said.

While BCG is not a generic injectable — it is a live, weakened bacteria that spurs the immune system — it is vulnerable to supply disruptions for some of the same reasons. It has been in short supply three times in the past seven years.

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Some patients are angry at Merck, saying there is no shortage of Keytruda, the company’s blockbuster immunotherapy drug that is used for several advanced cancers and has a list price of $150,000 a year. “Why, if there’s a medicine out there that works, can they not make enough of it?” said Fred Emmett, a patient at Fox Chase Cancer Center in Philadelphia.

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Merck’s Nally said such arguments are unfair. The company has “turned over every stone to increase production,” he said, but ultimately can’t meet rising demand. He said each batch of Merck’s strain, called TICE BCG, takes three months to make and can be ruined by the slightest contamination.

About 80,000 people were diagnosed with bladder cancer in the United States last year, and an estimated 17,000 people died of the disease. As many as 30,000 new patients annually are candidates for BCG, a liquid delivered to the bladder by catheter. Thousands more are eligible for maintenance doses for up to three years.

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BCG, or Bacillus Calmette-Guérin, was developed as a tuberculosis vaccine more than a century ago at the Pasteur Institute in France.

Sanofi Pasteur was once the leading BCG producer for the United States but shuttered its aging Toronto BCG plant in 2011 after the FDA found widespread contamination. Eventually, it left Merck, which had been supplying less than 30 percent of the U.S. market, as the sole BCG producer for the United States.

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Merck said it has increased production of BCG TICE from 300,000 doses annually in 2012 to about 870,000 today. But global demand is running at more than 1 million doses. Earlier this year, the company began allocating the drug to distributors based on past use. Medical groups developed guidelines for using the reduced supply, giving top priority to new patients.

Yet some of them are having trouble getting BCG and are opting instead for less effective chemotherapy. Others are receiving partial doses, which data indicates is effective. Many hospitals and clinics have halted maintenance therapy like Archuleta’s.

In late April, NYU Langone Health had no BCG and 20 patients awaiting treatment, said urologist Gary Steinberg. The hospital recently acquired some BCG, but not enough for all the “patients in the pipeline,” he said. At Fox Chase, urologist Alexander Kutikov said he is getting patients referred by Philadelphia urology practices whose BCG supplies are “totally depleted.” Clinical trials testing new treatments against BCG have slowed, he said.

Meanwhile, researchers are racing to find alternatives. A major clinical trial is scrutinizing a strain used in some Asian countries.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said the agency would consider using “all available expedited programs” to bring appropriate BCG products to the United States. Given the global shortage, however, it isn’t clear any foreign producers have extra supplies, he said.

While the FDA works to avert shortages, it has limited authority. Companies are required to report emerging shortages, but the agency can’t order them to make more of a specific drug. Last summer, Gottlieb appointed a task force to look more closely at shortages, including whether the United States needs a list of “essential drugs” that might get government subsidies.

Last year, several hospitals created Utah-based Civica Rx to supply generic drugs that are in short supply. Sen. Elizabeth Warren (D-Mass.), a presidential candidate, has proposed legislation that would create a new office within the Department of Health and Human Services to produce certain generic drugs.

Archuleta, meanwhile, waits for word on whether he’ll be able to get treatment. “I am hoping the shortage is just another bump in the road,” he said.