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A year ago, I became aware of Bladder Cancer Canada was trying to get Russian strain BCG approved for Canada to alleviate the MERCK TICE BCG shortage in Canada. I raise some concerns of this approach. Below is the list of my concerns.
Background : The currently licensed tuberculosis vaccine, attenuated Mycobacterium bovis strain Bacillus Calmette-Guérin (BCG), was originally derived from M. bovis. The strains used are all progenies of the original strain attenuated by Calmette and Guérin during 1909–1921. In the absence of lyophilisation or freezing and the production of seed-lots until the 1960 s, the propagation of BCG through continuous passage under different laboratory conditions resulted in the generation of daughter BCG strains with different morphological, biochemical and immunological characteristics. Some of these daughter strains have lost genomic regions that affect their antigenic content, potentially changing their protective efficacy. (** see the research paper published in 2015 in Nature). In other words, the efficacy of BCG of different strains can be different. In 2012, due to the discovery of mold in the Connaught strain BCG production line of Sanofi Canada, the production of Connaught strain BCG was halted and eventually the production facility was shut down due to the lack of the buyer. This is when the BCG shortage started and MERCK increased their production of TICE strain BCGs. The current shortage of TICE strain BCG by MERCK has been going over a year and BCC was informed by MERCK that the current BCG shortage will continue throughout 2020. To alleviate the problem, Bladder Cancer Canada has informed that it is working with Health Canada to allow the use of Russian strain BCG. That is where we are at now.
Below are concerns I have to Russian strain BCG for bladder cancer patients in Canada.
1. Russian strain BCG is not the same as TICE strain BCG, which should require clinical trials to determine especially its efficacy and safety. Our neighbour US had chosen Tokyo-172 strain as a possible supplement / replacement of TICE strain BCG of MERCK. They already started the phase III clinical trials at 150 locations in multiple states led by SWOG. The clinical trial ( NCT03091660 ) had started in Febrary, 2017 with the primary completion date Feb, 2022. The clinical trial involves about 1,000 patients. In Canada, we have not even started the clinical trial of the proposed Russian strain. If it is going to take 5 years for the clinical trial of Tokyo strain, then it seems that it would take and we should take similar length to prove the Russian strain BCG has equivalent efficacy and toxicity as the current TICE strain BCG.
2. Adoption of Russian strain BCG will alienate bladder cancer patients from benefiting the result of BCG related research in US. Up to now, most research done in US involving BCG for bladder cancer could be applied to bladder cancer patients in Canada because the patients in both countries have been using the same TICE strain BCG. If we use Russian strain BCG, we are no longer comparing apple to apple.
3. The reliability of the manufacturer. I do not know if we are going to have a manufacture here in Canada for Russian strain BCG or we are going to import from a foreign country who is currently manufacturing the Russian stain BCG. Even such big pharmaceutical company with $42B revenue company got into the production problem which caused the current shortage. Still, because of the big pocket of the company, it was able to ramp up the production to reduce the impact of the shortage. If I am not wrong a start up company called Veritypharm seems to be the company who wants to market Russian strain BCG. I see they Canadian doctors on their scientific advisory board. The company was established in 2016 in Canada. How can we bet the lives of bladder cancer patients to unproven company? Also, their business model does NOT fit to such essential drug like BCG which needs to be provided at low cost. Their corporate presentation says “Verity Pharma – Canadian specialty Pharma focus in high demand medical products that relevant Rx Products and currently in short supply from the market. A low risk stable business focused on high profit product”. I do not know who put seed money to Verity Pharm. But their business model for intravesical BCG must be to get the BCG from some country who sells the BCG cheap and sell to Health Canada. I do not know what kind of sweet deal they are proposing to Health Canada. They may be saying to Health Canada can save millions of dollars by using their imported BCGs. I do not know. I am just guessing as I used to be in business development field myself.
BCG is the essential drug for Non muscle invasive bladder cancer patients in Canada. We want a reliable, stable supplier we can bet our lives on. MERCK says that they are not making money from selling intravesical BCG. It is okay because they can afford it. Because they are making money from other drugs, e.g. Merck makes $8B a year from Keytruda, the immunotherapy drug which is used for advanced stage bladder cancer. Some analysis is predicting the business from KEYTRUDA itself will grow to be over $20B buy 2025. The cost of running their TICE strain BCG production line is a peanut compared to the revenue they are getting from KEYTRUDA. So, stick to MERCK as the main supplier. As a supplement supplier, I would choose Tokyo-172 strain just like USA. In this way, any research Canadian researchers do BCG and what US researchers do become relevant. Canada does not have to spend much to qualify the BCG as US is already doing the clinical trials on Tokyo-172, comparing its efficacy against TICE strain BCG. I believe Tokyo-172 is being manufactured by Japan BCG company, which has been in existence since 1952. All Health Canada has to do is to facilitate to import Tokyo-172 directly from Japan. I am a non muscle invasive bladder cancer myself. I do not want to bet my life on a start up company. BCC should not put bladder cancer patients at risk by recommending Russian strain BCG unless all three concerns are removed.
Joe
Links to the company website and corporate presentation of Verify Pharm.
Link to the published paper by Nature for the efficacy difference among different BCG strain.
https://www.nature.com/articles/srep15443
Link to Japan BCG corporation
http://www.bcg.gr.jp/english/index.html
Verity would not be manufacturing BCG in Canada, the product would be manufactured as it is today by SIIPL, and distributed in Canada by Verity. Of course this would need the approval of Health Canada.
Toronto, Ontario, November 1, 2018 — Verity Pharmaceuticals Inc. is pleased to announce submission of the New Drug Submission (NDS) to Health Canada for review and approval of VERITY-ONCO-BCG (Bacillus Calmette–Guérin) as an antineoplastic agent for bladder cancer instillation. The drug will be marketed in Canada through an exclusive licensing agreement with Serum Institute of India Private Ltd. (SIIPL), a world leader in the development and manufacture of vaccines. Under the terms of the agreement, SIIPL will supply the finished product and Verity will market and distribute to the Canadian market.
ABOUT SIIPL
Established more than 50 years ago, and located in a state-of-the-art facility in Pune, India, SIIPL is the world’s largest manufacturer of vaccines by number of doses produced; having its reach in over 170 countries. 65% of the children in the world receive at least one vaccine manufactured by SIIPL. Licensed for manufacture of the BCG vaccine in 2001 and prequalified by the World Health Organization (WHO) in 2003, SIIPL has since supplied the BCG vaccine to more than 130 countries. “Our collaboration with SIIPL is off to a great start and their assistance in preparation for our NDS has been superb. We look forward to a long-lasting relationship and to providing a steady and reliable supply of BCG to the Canadian market.” – Howard Glase, CEO, Verity PharmaHi Jack, I also suspected that SIIPL will be the manufacturer https://www.seruminstitute.com/product_uro_uncology.php. The other manufacture in India is manufacturing BCG with Denmark Strain.
Not that I question the manufacturing capability or the fact intravesical BCG has been used mainly in India successfully. Just that I would never understand the logic behind how Health Canada can approves the different strain BCG , which is manufactured by the different manufacturer without clinical trials. I have no idea why BCC has come up with the Russian Strain BCG in the first place when our neighbour US has been working on Tokyo Strain BCG since 2017. Joe
Bladder Cancer Canada is deeply concerned about the current BCG shortage and its effects on the treatment of bladder cancer patients. We are urging Health Canada to bring a second supplier of BCG to Canada.
Health Canada would need to determine the 2nd supplier not BCC.
Jack
I do not know why it is Health Canada taking to make the decision. They could have initiated clinical trials of whatever BCG strain they are thinking of. We are three years behind in that area. Anyway, I hope Health Canada will also look at the company who is going to be supplying BCG. Especially, if Health Canada approves another BCG in addition to the current MERCK TICE Strain, they will not approve some other BCG strain in Canada. So, I hope Health Canada will look at who will be the supplier for the new strain of BCG. I suppose Verity which plans to supply Russian strain BCG from the manufacture in India is the front runner. I am assuming Verity Pharm is going to have an exclusive distributorship to sell SIIPL BCG vial. It means Virity Pharm will have control on the market on pricing except MERK Tice BCG. Verity Pham’s business model has similar traits to Valeant Pharmaceuticals which was infamous of buying the license of orphan drugs and raised the price by 3000%. I just do not feel comfortable that we let such company takes control of supply and the pricing of the essential treatment for non muscle invasive bladder cancer patients, which I am one of them. I hope Health Canada also has business acumen in determining the right supply chain in dealing with such critical drug for us. Well, enough said. Thank you BCC for providing me a place to express my concerns !!
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