Longtime drug shortage leads to substandard care for thousands of US bladder cancer patients

Resilient Drug Supply
Drug manufacturing

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The End Drug Shortages Alliance (EDSA) is urging pharmaceutical manufacturers to boost manufacturing of Bacillus Calmette-Guerin (BCG), an essential drug for bladder cancer that has been in shortage since 2019.

Because of the shortage, an estimated 8,333 US patients with moderate to advanced bladder cancer aren't receiving optimal care, EDSA said in a white paper based on a November 2022 survey of academic health centers, health systems, and physician practices.

"The shortage of BCG is extremely problematic," said David Margraf, PharmD, PhD, pharmaceutical research scientist at the Resilient Drug Supply Project (RDSP), part of the University of Minnesota's Center for Infectious Disease Research and Policy (CIDRAP), publisher of CIDRAP News.

"It possesses many of the traits we worry about when making treatment decisions for patients," he said. "As a result of this shortage, patients are left with less than optimal options depending on their disease severity: either forego therapy or resort to alternative treatments that have higher risks of adverse events and poorer outcomes."

Adverse effects, disease progression

To conduct the survey, the patient-advocacy organization Angels for Change worked with fellow EDSA member and healthcare-improvement company Vizient. EDSA is a national collaboration of healthcare providers, group purchasing organizations, drug manufacturers, distributors, and policy experts working to address the supply chain challenges that lead to US essential-medicine shortages.

As a result of this shortage, patients are left with less than optimal options depending on their disease severity: either forego therapy or resort to alternative treatments that have higher risks of adverse events and poorer outcomes.

David Margraf, PharmD, PhD

Of the 20 survey respondents, 62.5% said they had to switch patients to suboptimal therapies, 37.5% used substandard BCG doses, and 20% couldn't source any BCG.

"Alternatives to BCG therapy are associated with many negative consequences, including substantial adverse effects from traditional chemotherapeutic agents, risks of disease progression with reduced-dose BCG instillations [into the bladder], and premature loss of an organ with earlier cystectomy [bladder removal]," the authors wrote.

In addition, nearly 80% of institutions said they had no formulary restriction or protocol to conserve BCG, which could rapidly deplete supplies and lead to inconsistent patient care.

Margraf said the shortage has implications for global public health beyond bladder cancer. "BCG is a vital component of tuberculosis prevention, particularly in countries where TB is still a major public health concern," he said.

"The shortage of BCG may exacerbate the already alarming burden of TB in these countries and put more lives at risk," he added. "It is essential that we work towards finding solutions to address the BCG shortage and ensure that patients and public health programs have access to this essential medication."

Only one global BCG supplier

The white paper reports that Merck has been the only global BCG supplier after Sanofi Pasteur began to experience production problems and discontinued it in 2017. From 2020 to 2022, Merck was able to only slightly increase BCG supplies.

Used to treat moderate- and high-risk bladder cancer since 1976, BCG is regularly instilled into the bladder for at least 6 to 12 months. This year in the United States, a projected 82,000 people will be diagnosed as having bladder cancer, and 17,000 will die.

"The current market is only producing 69% of the estimated BCG need based on 2018 baseline volume and an assumed bladder cancer growth rate of 2.5%" over the next 5 years in the United States due to an aging population and related risk factors, the paper said. An annual supply gap of more than 150,000 BCG vials could result.

The report's appendix summarizes strategies to optimize BCG use. In late 2020, Merck announced plans to build a new manufacturing plant in North Carolina that could triple its BCG production, but a January 2023 announcement said the facility won't be completed for another 3 to 4 years.

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