- Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most common intravesical immunotherapy used to fight early-stage bladder cancer.
- U.S. providers and patients have been challenged in accessing BCG due to limitations in manufacturing capacity, resulting in worldwide shortages.
- Premier’s Pharmacy team recently developed an overview document summarizing the therapeutic use of BCG and the current-state management approach given constraints. What follows in this blog is a summary of the publication.
While progress has been made in improving access to many at-risk products, shortages of drugs and therapies vital to patient care remain a vulnerability for U.S. healthcare providers.
Bacillus Calmette-Guérin is made from a strain of Mycobacterium bovis ─ the same bacterium used to create the tuberculosis vaccine[i]— and is an effective immunotherapy that reduces the risks of recurrence and progression in patients with high-risk, non-muscle invasive bladder cancer (NMIBC)[ii]
The only agent approved by the U.S. Food & Drug Administration (FDA) as a primary therapy for bladder cancer[iii], BCG has experienced ongoing shortages with global demand outpacing current manufacturing capabilities and supply[ix].
Healthcare providers deliver BCG immunotherapy directly to the bladder through a catheter. While other agents have been used to treat bladder cancer, none has surpassed the effectiveness of BCG, which can eradicate the cancer in approximately 70 percent of patients who meet the following criteria:
- The patient is immunocompetent
- The tumor burden is small
- BCG makes direct contact with the tumor
- The dose is adequate to elicit a reaction
Background: A Market Disrupted
Many drug shortages, including shortages of BCG, are the result of long-standing marketplace dynamics – namely, a lack of competition that creates overreliance on just a few manufacturers, which are operating at capacity and therefore can’t accommodate demand surges or supply disruptions.
Few companies produce BCG for oncotherapy and NMIBC and export it globally[v]. It’s a complicated drug to produce that takes three months or more to cultivate in a rare, special breed of potato[vii]. BCG is highly effective, but generates low margins, with a list price of $157 for a six-week dose[viii] — and in 2012, there were two makers of the drug.
That same year, an unexpected event led to the closure of a Canadian factory producing and distributing BCG, which at the time, was one of the main sources of supply for North America and Europe — the regions with the highest incidence of bladder cancer around the world.[ix] Following its plant closure in mid-2017, the supplier confirmed that they were exiting the market.
During the last several years, increasing global demand for bladder cancer treatment has exacerbated BGC supply constraints, even as suppliers have ramped up production. In January 2021, Merck — now the only manufacturer and supplier of BCG to the United States — announced the construction of a new production facility in North Carolina that will allow it to triple their output of BCG.[x] But it is expected to take several years for the facility to come online.
What We Can Do
BCG shortages and have led to a rethinking of clinical treatment guidelines and conservation strategies. Suggested alternative management approaches include limiting access to low-risk patients, reducing BCG dose size or strength, prioritizing chemotherapy ahead of BCG, and limiting the use of maintenance therapy. Premier members offer their perspectives:
With 19 hospitals, two senior living communities, neighborhood health centers, physician practices and clinics, home care and hospice services, Centura Health serves communities across Colorado and western Kansas. Centura Health’s Director of Pharmacy & Shared Services Joshua Schwiesow notes: “We have experienced ongoing availability issues with BCG, and while we have largely received allocation when needed, certain instances require us looking into substitutions such as mitomycin if allocation is unavailable.”
MetroHealth operates four hospitals, four emergency departments and more than 20 health centers and 40 additional sites throughout Cuyahoga County Ohio. Jan Kover, Hematology and Oncology Pharmacy Specialist for MetroHealth Medical Center shares this guidance: “We have used both the 1/2 and 1/3rd BCG dosing depending on availability and patient tumor grade.”
Notably, the following provide specific clinical practice guidelines and recommendations for BCG treatment:
- The American Urological Association and the Society of Urologic Oncology recommendations for BCG treatment in NMIBC.[xi]
- The National Comprehensive Cancer Network® (NCCN) clinical practice guidelines for bladder cancer treatment.[xii]
- The NCCN guidelines recommend BCG therapy for urothelial carcinoma of the prostate, primary carcinoma of the urethra, and non-metastatic low-grade tumors of the renal pelvis. Clinical trials are also currently underway to explore BCG treatment for fibromyalgia and diabetes.[xii]
The lack of BCG availability has also led to the exploration of new treatment options for patients with several options being evaluated in an aim to improve BCG’s efficacy or to combine it with other chemotherapeutic or immunotherapeutic options that may also improve its effect. While intravesical chemotherapy can be utilized to some extent, currently BCG remains the treatment of choice for many patients.
Around BCG shortages, and overall in the Pharmacy space, the power of the Premier alliance connects people, data and knowledge to share intelligence, mitigation efforts and conservation strategies, and critical best practices with our members. Educational sessions, committees and other key forums provide visibility into what pharmacists and healthcare providers are facing, what’s working and what isn’t — and how we can tackle challenges together.
Now and always, Premier will continue to share vital education, recommendations and best practices — and pursue crucial strategies to help our members get access to vital therapeutics.
Standing together with our members and in collaboration with stakeholders across the supply chain, we will continue to take action — our commitment to protect providers and patients from pharmaceutical supply disruption will never waiver.
For more on this topic:
- Download your copy of the INSCRIPT thesis on drug shortages today.
- See Premier’s guidance for providers to reduce fluid shortage workarounds and support greater efficiency.
- Learn more about ProvideGx® — the industry-leading program delivering critical drugs pharmacists and clinicians need to serve patients.
[i] TICE® BCG (for intravesical use) [package insert] https://www.fda.gov/media/76396/download.
[ii] Babaian KN, Schwartz BF. Bacillus Calmette-Guérin immunotherapy for bladder cancer. https://emedicine.medscape.com/article/1950803-overview.
[iii] Babaian KN, Schwartz BF. Bacillus Calmette-Guérin immunotherapy for bladder cancer. https://emedicine.medscape.com/article/1950803-overview.
[v] Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025668/#CIT0022.
[ix] Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21492.
[x] Merck to construct new facility in the United States to expand manufacturing capacity for TICE® BCG. https://www.merck.com/news/merck-to-construct-new-facility-in-the-united-states-to-expand-manufacturing-capacity-for-tice-bcg/.
[xi] Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline (2020). American Urological Association/Society of Urologic Cancer. http://www.auanet.org/guidelines-and-quality/guidelines/bladder-cancer-non-muscle-invasive-guideline.
[xii] Flaig TW, et al. Bladder cancer – Version 2.2022. National Comprehensive Cancer Network. May 20, 2022. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf.