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.
“My doctor says he feels really bad about it, but I keep wondering: How could this happen in this day and age?” he said.
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.
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.
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 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.
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.
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.”
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 have 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.
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.
Deborah Norris said her father, Cecil Northrup, 83, was diagnosed in 2010 with bladder cancer that returned in 2013 and again 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.
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.
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.
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.
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 takes three months to make and can be ruined by the slightest contamination.
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.