2019 BCG Shortage BCG Background and Shortage Explanation

welcome to Beijing beacon special update 2019 BCD shortage understanding your treatment options my name is Stephanie Chisholm and I'm the director of education and research at beacon I'm joined today by Baylor College of Medicine neurologist dr. Seth Lerner and UT Health San Antonio urologist dr. Robert spa tech along with swagg beacon patient advocate Rick banks to discuss strategies and viable alternatives currently available for patients who are not able to get ECG whether it's as a result of the current BCT shortage or for other reasons related to their diagnosis welcome it's a pleasure to have you all with us thanks so much for joining us let me first introduce our presenters dr. Seth Lerner is professor of Urology and holds the Beth and Dave Swamp chair in urologic oncology in the Scott Department of Neurology at Baylor College College of Medicine he's co-chair of the National Institutes bladder cancer task force and bladder cancer disease working group for the Cancer Genome Atlas Project he chairs the local bladder cancer committee of SWOG and serves on the board of directors for the bladder cancer advocacy network dr. Roberts photic is an associate professor and chief of the division of urologic oncology at the University of Texas Health San Antonio his practice is devoted to the care of bladder cancer patients and he's built the center of excellence for invasive bladder cancer for patients in from the south the southwest Texas region dr. Swan Tech is actively involved in clinical trials for bladder cancer and runs an nih-funded cancer immunology lab he focuses on the role of innate immunity in mediating cancer immune surveillance and cancer therapy mr. Rick Baynes is a bladder cancer and prostate cancer survivor and has worked as a patient advocate in a variety of roles including research advocacy government lobbying educational support support groups one-on-one support and fundraising as a research advocate he serves as the member of the National Cancer Institute Council of research advocates co-chair of the NCI patient advocates in committee one of two NCI genitourinary specific scientific steering committee patient advocates that ended up in the end of last year and he's also served as NCI cancer care direct delivery scientific steering committee patient advocate and chair of the swag patient advocate committee so we're really excited to have all of you with us this evening so thanks so much for joining us I did want to provide a quick update as of March 25th 2019 on what beacon has been doing and what we know about the PCT shortage we have met and will continue to meet with Merck to encourage quicker production of BCG to meet the needs of all BCG patients we are meeting with the FDA Center for Biological uation and research to encourage strains of BCG used in other countries to be allowed to be introduced into the United States we're meeting with other pharmaceutical companies that want to introduce new strains and alternative immunotherapy treatments to fill the gap and meet patient's needs and beacon has been asking the FDA to fast-track the approval process to get those new strains into the United States market more quickly please watch for updates on our website WWE an org forward slash 2019 BCD shortage bladder cancer and we will keep you updated there so now I'm going to turn this over to dr. Spock who's going to introduce you a little bit to the background of BCG Thank You Stephanie and welcome everybody let's go to the next slide which shows the history yes thank you so BCG was originally developed not for bladder cancer but for the vaccination against and prevention of tuberculosis at the beginning of the 20th century tuberculosis was rampant and effective treatments such as the antibiotics that we have today were not available what was clear though was that if a person was infected with tuberculosis and survived the infection that they would been they would then be subsequently immune to any additional exposure and this is the idea behind vaccinating people prior to the exposure this is the power of our immune system to form a type of memory towards particles that are foreign including bugs such as tuberculosis so dr. Albert Calmette and dr. Cal male grin worked tirelessly over two decades to develop a vaccine to treat to treat through oculus so how do they do this and what are the features of an effective vaccine well an effective vaccine requires two things number one it must be a bacteria or a an organism that is weakened enough so that it doesn't cause any illness when it's given but on the other hand and number two is that it still must be intact enough to trigger a good immune response for their discovery of BCG they grew bacteria in their laboratory actually on potato slices and they used various animal models to test their vaccine so the vaccine changed over four years and they would test it in different models until they developed the ideal conditions which are again that it's weak enough not to hurt the animal but strong enough to elicit an immune response in 1921 they had finally succeeded in creating BCG and they performed the first vaccination on an infant whose mother was severely afflicted with tuberculosis the infant survived and soon this new vaccine which was named bacillus Calmette we're in or BCG and recognition of these scientists then distributed all over the world sadly Albert Calmette who died in 1933 died without having had the satisfaction of knowing the widespread success of BCG in preventing tuberculosis not to mention the enormous benefit that BCG would have for patients suffering from bladder cancer at the time of his death he was still defending the safety and the value of BCG next slide please thank you so from its origins in 1921 how did we get to using BCG for treating bladder cancer so as I mentioned in 1921 BCG was widely distributed throughout the world to various physicians and scientists for use to prevent tuberculosis and for use to do research and this was sent to Russia Japan South America North America and it's used to prevent tuberculosis was slowly and gradually adopted over the next century today in the United States it's not used routinely but in other parts of the world such as Africa and parts of Europe it's still used to prevent tuberculosis and infants are given the vaccine important discoveries were made in the 1950s that led to experimentation with BCG when one important discovery was the idea or the fact that some animals that had been given BCG were found to be resistant to tumor growth in two subsequent tumor challenge and these observations were later carried out and made in humans as well and so the idea that is that if BCG can somehow enable the body to prevent tumor growth then maybe we could use BCG to actually treat tumors the first tumor that was treated with BCG was skin tumor melanoma and the BCG was actually injected directly into the - murmurs and there are reports of spontaneous resolution or disappearance of melanoma skin tumors through BCG injection BCG is no longer used to treat melanoma there's different medications used now but that early observation prompted investigations into other tumor types including bladder cancer what BCG needs to work is it needs close contact with the tumor and in bladder we have this remarkable ability to administer agents directly to the bladder mucosa or directly to bladder tumors through a catheter in the 1970s dr. Morales Canada performed the first human trial using BCG insulation and had some remarkable observations of efficacy subsequently large clinical trials were conducted including a large important trial by the Southwest Oncology Group which showed efficacy of BCG and initiated the widespread use of BCG for preventing bladder cancer and for treating certain types of bladder cancer I'm in 1990 the FDA approved BCG for treatment of bladder cancer because the next slide we can talk about how BCG is given and why that's done so the BCG is often lumped the the treatment is lumped into two different courses the induction and the maintenance the induction is the kind of in the initial treatment phase and it's a six-week treatment phase BCG is as I said through a catheter a Foley catheter is placed into the bladder and it's instilled in a solution of water and allowed to just rest there in the bladder for a period of two hours and then the Foley catheter is removed the BCG is discarded after two hours and this is given weekly for six weeks as the initial induction course that is often done relatively soon after the the initial diagnosis so that the bladder tumor is removed by a resection endoscopic resection but we often call it trans urethral resection and then enough time is allowed to for the bladder to heal that can be anywhere from two to six weeks two to four weeks and BCG is in started and the installation is performed in the clinic once a week for six weeks maintenance treatments are given once a week for three weeks and they're roughly given every six months although we add in an additional one at three months following the tumor removal for the scheme there is that the maintenance treatments are given at three months and then six months from tumor removal and then every six months for three years now why give so much BCG is that really necessary well there's clear evidence that giving maintenance BCG this three years of treatment can significantly and substantially decrease the likelihood of tumor relapse and that was shown in another large a swab trial looking at the the benefit of maintenance therapy so even though it's sometimes onerous to give that amount of BCG and sometimes it takes a lot of effort on both the patient in the physician to do so there's clear level one evidence that this is effective now next slide will show us these different strains of BCG and so I'm the question I ask us so are all BCG vaccines the same and why do we have more than one BCG that see as early as 1921 the cultures of ECG were distributed by the Pasteur Institute to laboratories around the world in implementation of BCG varied from country to country there are several fascinating histories that have been written about these specific strains and how they revolutionized tuberculosis in the country but because BCG was a live vaccine it to live bacteria it was necessary to culture this on fresh media every every few weeks and despite efforts to standardize the growth and the preparation of the media there were lots of different conditions that were used in these different production facilities throughout the world and so what happened was that changes in the BCG bacteria took place in different countries throughout the world these changes were genetic changes stayed with the bacteria and as a result of decades and decades of of change we now have bacteria that are very different in the 1960s the system was then converted to where there was a standardization in what we call using seed Lots so that 1961 the changing or the genetic nuances and changes of these big BCG kind of stopped but since but but before that time all the changes took place and so now strains that are currently used today such as Tokyo strain and Thai strain are they're different because of these evolutionary changes that took place in different labs next slide so why are there shortages supply does not meet the demand is the supply and demand is one potential reason for a shortage so previously another strain was made by a company out of Canada the cannot strain and that company no longer makes not there was also another company longer time back that made it another string called the Armand frappe year that company no longer matrix train so in the United States patients are limited to one manufacturer Merck that makes the theis BCG stream and now Merck is supplying theis BCG for many countries throughout the world and it's just a matter of the the supply not meeting the demand growing BCG and propagating it is difficult it takes expertise in this area and as you can imagine with a bacteria alive bacteria if there's any role you know contamination that could have serious consequences to the production so contamination and factory problems such as that have led to partial shutdown of factories that has been resulted in manufacturing problems also because of the prior scare in experience with dealing with shortages there's been hoarding big hospitals can acquire large amounts of BCG and store it which can result in temporary shortages so in the next slide please Stephanie so I'm going to