Bob Field was set to kick off his second course of BCG — a potent immunotherapy that treats his fast-growing bladder cancer. Instead, the New York City banking executive got a call from his urologist’s office, canceling that week’s appointment: They were running low on vials of BCG and rationing their dwindling supplies. Field was no longer eligible.

It wasn’t just one doctor’s office. There’s a critical national shortage of BCG, a biologic drug that has been used for decades and that is a remarkably effective medicine. Many smaller clinics have already run out of the lifesaving drug, and larger hospitals — including New York’s Memorial Sloan Kettering Cancer Center, where Field is being treated — have changed their policies on distributing BCG to prioritize newly diagnosed patients with active cancers.

“In a word, I’m horrified. Depressed, annoyed, angry,” said Field, 72, who is now calling hospitals and clinics across New York to see if he can gain access to the drug. “This is a proven, time-tested means of helping people prevent recurrences of bladder cancer — and it’s suddenly unavailable. So there’s some stress.”

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Drug shortages are alarmingly common in the U.S., with health care providers often scrambling to make do without sufficient supplies. Those shortages occur for any number of reasons — natural disasters at productions plants or surging demand caused by an outbreak, for instance. But there are also commercial forces at work.

Companies have very little incentive to manufacture a drug like BCG. Although it’s been used to fight cancer since the 1970s, it isn’t easy to produce. And priced at a relatively modest $100-$200 a dose, it’s not a drug that companies are rushing to make, even if it’s no longer patented; right now, Merck is the only manufacturer for the U.S. and European markets.

BCG, in other words, is an example of a medically important drug that gets neglected because it fails to generate a lot of money for its maker.

“This BCG shortage is a huge deal,” said Dr. Robert Abouassaly, a urologist at Cleveland Clinic. “We don’t have any alternatives that are as effective for these patients.”

Merck acknowledges supplies are short and has expressed sympathy for cancer patients in need. At the same time, it says it is already working at capacity to produce more of the drug.

The company has every intention of continuing BCG production for “the foreseeable future,” according to Tyrone Brewer, vice president of global oncology marketing at Merck.

“It’s not our intent that we’ll use this drug to increase our margins,” Brewer said. “This is not about the profits, but a mission to save and improve lives.”

BCG, short for Bacillus Calmette-Guérin, is one of the earliest examples of immunotherapy in medicine. The drug was first used as a tuberculosis vaccine in 1921: It’s a live, but weakened, strain of a tuberculosis-causing bacteria called Mycobacterium bovis.

Researchers began to notice that patients with tuberculosis had lower rates of cancer, prompting early study of BCG as an oncologic tool. In the 1970s, it was found that if the live, attenuated BCG bacteria were fed through a catheter directly into a cancer patient’s bladder, they revved up his immune system — stimulating T cells to attack tumors.

Ever since, BCG has been the standard of care for certain forms of bladder cancer. It beats out both surgery and chemotherapy in keeping bladder tumors at bay. It’s substantially cheaper, too.

There are about 80,000 new cases of bladder cancer in the U.S. each year, making it the nation’s sixth most prevalent cancer. About 20 percent of these cancers — specifically, those with high-grade, non-muscle invasive disease — can be treated with BCG. It doesn’t work for everyone, but the response rate is more than 70 percent.

Standard treatment calls for clinicians to continue checking for cancer every three to six months after initial dosing, and administer follow-on doses of BCG to ensure the cancer remains in remission. Those are the kinds of doses that have remained out of reach for Field.

For him and other patients in similar circumstances, the consequences are as emotional as they are physical.

Donna Hoff, a 71-year-old retired bookkeeper, had her bladder tumors surgically removed, then was put on a regimen of BCG combined with interferon, another drug that boosts immune response. So far, the cancer has not come roaring back. But she’s concerned that if her BCG maintenance treatment is abbreviated, it might.

“You’re never really in remission,” Hoff said. “It’s always sitting on your shoulder, waiting to return.”

Certain chemotherapies, such as gemcitabine or mitomycin, can be used in lieu of BCG. But their efficacy pales in comparison, said Dr. Robert Svatek, chief of urologic oncology at University of Texas San Antonio.

“There’s no question that BCG is more effective,” Svatek said. “Multiple trials have compared BCG to chemo, and every time it wins. It beats the chemo.”

Patients can also elect a more extreme route: complete bladder removal surgery, or the construction of a bladder-like pouch made out of intestine. The costs of these complex surgeries are in the tens of thousands of dollars, and require years of follow-up treatment.

As effective as BCG may be, creating a safe strain of a live tuberculosis bacteria is rife with complications. The process, start to finish, takes about three months — beginning with two months of horticulture. BCG is grown on a specific variety of potato, and that alone takes two months to grow. Once harvested, it’s brewed in giant vats over the course of a month. And plenty can go wrong.

Sometimes entire batches of drugs like BCG can get ruined if someone just pushes the wrong switch, or throws one wrong chemical into a big vat of the drug.

“I’ve seen that happen — just a big mistake, somebody puts in the wrong chemical, and several million dollars worth of a drug has to be discarded,” said Dr. Otis Brawley, a physician at Johns Hopkins and until recently the chief medical and scientific officer at the American Cancer Society.

Supplies of BCG have been erratic for several years, beginning in 2011, when the Food and Drug Administration inspected a Toronto vaccine laboratory where Sanofi (SNY) was manufacturing the drug and found 58 different instances of mold after a flood. The FDA promptly shuttered the lab, triggering the first of a series of BCG shortages.

The shortages continued, on and off, as Sanofi dealt with regulatory blowback. It stopped BCG production in 2016, leaving Merck to supply the drug for most of the world. But right around the same time Merck began experiencing its own manufacturing issues.

When Sanofi attempted to sell off its BCG-making assets at a discount, there were zero takers.

“Companies like Merck don’t make money off of BCG,” said Dr. Benjamin Davies, a professor of urology at University of Pittsburgh. “So there’s very little incentive, outside of altruism, to make this better.”

When shortages of BCH hit, there are ripple effects.

A 2017 New England Journal of Medicine piece authored by Davies found list prices of chemotherapies used in bladder cancers spiked dramatically during a 2014 BCG shortage: The list price for mitomycin jumped by 99 percent from $436 to $869 for the 40-milligram dose. And between 2012 and 2015 — years of BCG drought — annual Medicare Part B spending on mitomycin increased from $4.3 million to $15.8 million.

Companies don’t have their plants producing batches of the same drug year-round — they tend to tool up a plant to manufacture a drug for a finite amount of time, churning out a massive batch. They’ll typically sell that over the course of a year or two.

This is how Merck doles out its BCG — selling it in bulk to hospitals and other large-scale providers, allocating it proportionally around the world, based on need. The company expects to produce anywhere from 600,000 to 870,000 vials of BCG this year, though isn’t providing a timeline on when the drug will ready. It’s also exploring ways to increase BCG output, Brewer said.

At the same time, companies in Japan, Canada, and Europe are developing their own strains of BCG, however — and if they’re ultimately approved by the FDA, they might be able to allay future shortages of the drug.

For now, however, some patients will struggle to get access, just as other patients do with a host of other treatments in the U.S. health care system, said Erin Fox, senior director of drug information services at University of Utah. Common hospital provisions like IV fluids and morphine are constantly in production limbo.

That doesn’t make the shortages any less frustrating. “We pay the highest prices of any country, so these shortage situations shouldn’t happen like this,” she noted.

If there’s a silver lining to the BCG situation, Fox said, it’s that there’s growing evidence that smaller doses show efficacy in battling bladder cancers.

Indeed, to help prolong the supply of BCG, most urologists wind up dividing the dosage into thirds. There are studies, actually, that suggest that these lower doses are similarly effective in treating bladder cancer.

The Bladder Cancer Advocacy Network, a Maryland-based patient advocacy group, along with the American Urological Association and several other physician groups, have come up with treatment guidelines to help navigate the shortage. The suggestions include dividing up doses, and stopping maintenance therapy entirely, as was the case with Fields.

Dr. Karim Chamie, an associate professor of urology at University of California, Los Angeles, said the BCG shortage hasn’t affected his practice just yet. But although the stockpile of BCG at UCLA is still in good shape, Chamie projects that will soon change.

“Urologists in the community have already hit a shortage, and they’re referring their patients to me,” Chamie said. “So my clinic’s clogging up with patients who need BCG — and they may be using some of the BCG I might have given someone else.”

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  • Hi Meghana: Could you tell me who this Bob Field is? I’d like him to help me to raise money to develop a better BCG immunotherapy which can save more lives for people who have Non-Muscle Invasive Bladder Caner. My name is Tsungda Hsu and I “may” old a key to advance our understanding of BCG immunotherapy. You can Google my profile and get to know me better or by calling me at my cell number 9175741928. I’d be happy to talk to you about my discovery that may revolutionize the research in BCG immunotherapy. Thank you so much for your attention. Yours, T. Hsu, a.k.a. KO. My email address is thsu01@yahoo.com. My cell number is 9175741928.

    • Hi: I was informed by NIH that my grant application to developed a better BCG immunotherapy just got trashed (Not Discussed) yesterday. Given this, I still strongly believe that my research into developing better BCG immunotherapy will save lives for people like you. So, I come here to look for your advices as to how I may better advance the BCG immunotherapy by an unconventional path. I can be reached by thsu@yahoo.,com. My cell number is 9175741982. Thanks.

  • My husband finished 6 weeks of BCG therapy in April. He has had no relief from burning urination and urgency. Is there a remedy for this?

  • Need massive financial changes to drug policies. Not done by a do nothing congress but by a mix of medical and non-medical businessmen.

  • Please tell Arthur to go to BCAN website and ask if anyone knows of available BCG in North Carolina and wish him much luck.

  • I have bladder cancer and have had 3 surgeries. It came back this time and had 11 tumors. Had surgery yesterday, 6-10-19 in Pinehurst, NC and was told this morning by my Dr. that I can’t get BCG due to the shortage and they only get 5 doses per week!!
    Really makes you mad at the system and our government for not doing something to stop the price gouging and shortage.
    Just hope I can survive until Vicinium is in in production.

    Only in America!!

  • Its a shame I was diagnosed with bladder cancer June 9th 2018 I had 2 surgery’s they took a tumor about the size of my thumb in June then I had a second spot on in by bladdet kt was cancer but it hadn’t started to grow luckily neither one was in the muscle I was treated with BCG after the first surgery I was suppose to start a year regiment in January of 2019 but was told that they were out they said it would probably me in May when they would recieve it around May they were sent about 14 vials that I was told it was enough to treat one patient I hope the company is proud of what there doing while there are people out here that needs this medication to survive will you please try to step up production worried patient

    • Hi: I am sorry to hear yiur story, but f I ask you to come to my laboratory to grow your own BCG for your own BCG immunotherapy which, of course, you have to discuss with your physician, how do you think? Before anything such as contacting your physicina or authority, would you contact me at 9175741928? This is not a fraud. You can Google me or search LinkedIn for my profile. Thanks. Tsungda Hsu

  • Crystal,
    See my comment from 2/19, below and contact me at media@physiciansagainstdrugshortages.com if you’d like to discuss.
    What STAT News, including Ed Silverman, Meghana and other so-called health care journos don’t understand—or want to take the trouble to understand—is that GPO/PBM middlemen are siphoning off money from drug makers in return for exclusive contracts. These predators are making all the money. That’s why HHS Alex Azar has called on Congress to end the PBM kickbacks (rebates), which would be achieved by repealing the unsafe 1987 group purchasing “safe harbor.” That would kill two predators with one stone: stop the skyrocketing prices of drugs sold through PBMs and GPOs and end the global drug shortage fiasco. For documentation, visit our website, http://www.physiciansagainstdrugshortages.com.

  • Thank you for this info. I may have missed it, but WHY aren’t the manufacturers making money? Charge what you need to charge. Didn’t say gouge, but make it worth the while. Or is 80,000 Lives a year not enough incentive. Does Merck manufacture the bladder bags and maybe they are more lucrative? I’m newly diagnosed High Grade Papillary Urothelial Carcinoma. No muscle invasion, so perfect candidate to go beyond my already 63 years on this earth. Has anything changed since this Feb 2019 article?

    • Fight Merke and all the others that are turning their heads. I am a BLADDER CANCER FIGHTER (BCF).
      I’m trying to get the news media to investigate and report the real reasons for the shortage. We have to make this public so our movement takes off and we win.

  • Hi,
    Is there any possibility you can get a message to Bob Field.
    I am heavily invested in a company called Sesen bio that have a drug called vicinium which is in phase 3 and will be looking to get FDA approval very soon. Vicinium itself is a bladder cancer drug treating NMIBC (non muscle invasive bladder cancer) it has a far superior safety efficacy than BCG and may well save Bobs bladder and more importantly his life.
    Best regards
    John.

    • Was looking for more information on vicinium? Having same problem with recieving bcg in mass hospital. Thank you.

    • Sesn bio – their website will provide contact information and status of FDA approval. There is a clinical trial being run through the NIH, combo of vicinium / imfinzi that is enrolling- contact piyush agarwal (piyush.agarwal@nih.gov) reference trial NCT03258593

    • Hi john: I am a researcher in BCG immunotherapy. I may hold a key to really advance the BCG immunotherapy and save people’s lives. Would you call me at 917-574-1928? My email is thsu01@yahoo.com. Thanks. Tsungda Hsu a.k.a. KO.

    • Hi Bob: Are your Bob Field? Would you contact me at 9175741928 or email me at thsu01@yahoo.com? I am trying to develop a better BCG immunotherapy which will benefit you, and me as well. No Gimme!

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