BCG Shortage Affects Bladder Cancer Treatment
Another shortage of Bacillus Calmette-Guérin (BCG) expected in 2019 has people with non-muscle invasive bladder cancer (NMIBC) and their physicians concerned about treatment. Global utilization and manufacturing issues associated with live BCG in recent years has resulted in product supply shortages.1 These shortages have slowed the overall usage of BCG and some physicians have rationed the product to those with the highest-risk during times of limited access.1
Bladder cancer is the ninth most commonly occurring cancer in the world, with the highest incidence in Northern America and Europe.2
BCG has been shown to invade bladder cancer cells where its presence triggers an immune response causing inflammatory changes in the bladder. The resulting reaction attacks cancer cells to stop or slow the regrowth of bladder cancer.5
How does BCG work?
BCG is the primary treatment regimen for non–muscle invasive bladder cancer. Candidates for effective treatment with BCG are NOT immunocompromised and have small tumors that are in direct contact with the implanted BCG causing a therapeutic reaction.4
Standard BCG treatment is done on an outpatient basis. It is administered once a week for 6 weeks followed by a maintenance regimen over a period of 1 to 3 years. Studies find BCG treatment effective in treating approximately 70% of patients with carcinoma in situ who meet the specific treatment criteria.5
Why the shortage?
There is a history of BCG shortages over the last 10 years. Because BCG is a live attenuated virus, there are safety precautions required in manufacturing. Two different drug companies, Sanofi and Merck, were manufacturing different strains of the BCG virus, and both experienced serious manufacturing complications.1,2
In 2012 Sanofi temporarily halted production in order to upgrade its manufacturing facilities. However, there were continuing production issues, which resulted in a 2016 announcement that ImmuCyst/TheraCys BCG, their live attenuated product, would stop production in mid-2017, with supplies likely lasting until 2018.1
Merck manufactures the TICE strain of BCG. It too experienced contamination issues at the manufacturing level, which resulted in a shortage. Merck reported that it took three months to grow a “batch” of BCG (a microorganism, not a molecule), and that potential contamination with other microorganisms resulted in production stoppage.6
Impact of BCG shortage on treatment protocols
For years, BCG treatment was indicated for the treatment of intermediate and high risk non-muscle invasive urothelial cancer of the bladder, including carcinoma-in-situ and high-grade stage Ta and T1 disease after transurethral resection.3,6 The shortages experienced have resulted in implications on patient care, with some practices and countries having placed limits and/or restrictions on the indications for BCG treatment. Only high-risk patients have been eligible for the limited BCG supply, and practitioners have suspended its use as a maintenance therapy.2
Physicians have tried lower dosages of BCG with vials being shared amongst patients being treated on the same day so as to avoid waste.6 These conservation strategies were put in place to increase the number of people who could receive BCG.
While the shortage of BCG is ongoing there needs to be a review of eligible indications, dosing amounts, schedule, and durations, as well as the consideration of alternative therapies.3,6 The selection of alternatives therapeutic agents requires patient-specific evaluation considering tumor type and location, kidney and liver function and other comorbidities. There is no single substitution for BCG live.3
BCG supply shortages will significantly alter clinical practice patterns. New treatment approaches for bladder cancer, including other BCG strains in development in other parts of the world, will require broader investigation. Identifying appropriate and effective treatments for specific classes of bladder cancer should lead to improved outcomes and the most effective use possible of BCG.
Drug manufacturing responsibility and access to safe and effective therapeutic treatments for cancer and other diseases is a worldwide concern.2 Drug shortages lead to increased market prices that can impact doctors and patients in the selection of and access to effective treatments.6
Update: For guidance from the American Urological Association regarding the shortage, click here.
Did you know that May is Bladder Cancer Awareness Month?