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Northwest Biotherapeutics is beginning to open the UK Specials Program to new patients, at a cost of treatment greater than GBP 300k. Below is a note that I have received recently, which details the requirements of the process. I have also attached the details of the costing scheme as a pdf document.
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BACKGROUND
Northwest Biotherapeutics conducted a DCVax -L Phase III clinical trial for adult patients between 18 and 70 years old who had been newly diagnosed with GBM. Trial participants met a number of specific inclusion criteria and had surgery at one of the 81 participating trial sites and met a number of other specific criteria to be accepted into the clinical trial. The clinical trial has completed its cohort (331 patients) in 2015 and has reached data lock.
The drug that is available on a very limited compassionate use / private pay for manufacture basis under the UK Specials regulation is an Autologous Dendritic Cell Vaccine (ADCV) that is manufactured from frozen tissue in the same manner as DCVax-L. The name for the drug that is manufactured under the UK Specials Program is ADCV to avoid confusion with the drug (DCVax-L) that was used in the clinical trial.
Northwest’s vaccine has been made available under the Specials regulation in the UK - this regulation permits patients to receive an experimental drug outside of a clinical trial. Unfortunately, the vaccine is not covered by the UK National Health Service (NHS) or private healthcare insurance.
REQUIREMENTS
In order to manufacture the ADCV, sufficient frozen, viable tumor tissue must be available to extract the tumor antigens/biomarkers to create the tumor cell protein lysate, the first step in manufacturing the vaccine.
Several grams of frozen tumor tissue are required, although it is sometimes possible to use less tissue in certain circumstances. The tissue should be stored without chemicals, preservatives (such as formalin) or paraffin. It needs to be “flash frozen” in a sterile container/cryovial and stored at –70 degrees C or colder. Unfortunately, tumor banks and pathology departments frequently use paraffin or other preservatives that render the tissue unusable for the ADCV process.
It is important to note that the tumor tissue used in the manufacturing of the ADCV must have been stored as excess diagnostic tissue that was not required for primary diagnostic purposes.
CONSIDERATIONS
Some surgeons use Gliadel wafers. If Gliadel wafers were used then an ADCV is not a treatment option because the chemo leaching from the wafer will also kill immune cells which enter the tumor cavity to fight residual tumor cells.
We will not be able to use the tissue of patients that tests positive for infectious disease such as Hepatitis, HIV, Syphilis, and the like. Before tumor tissue can be shipped to the UK, we will need a set of virology tests and to execute several transfer agreements with the storage bank.
The regulatory structure under which the UK Specials Program operates requires that all of the vaccine injections occur in the UK under the supervision of a UK physician participating in the Program.
When the time comes, your patient will be referred to a physician participating in the Specials Program and evaluated as to his medical eligibility to participate in the Program. If he is deemed medically eligible and is enrolled, he will need to be able to travel to the clinic in the UK to undergo a leukapheresis blood draw and all the vaccine must be administered in the London clinic (six doses injected in the upper arm, similar to a flu shot, are given in the first year).
The UK Specials Program is the only access point for Northwest’s ADCV vaccine. I'm afraid there is no regulatory provision for the vaccine to be administered anywhere else. Again, given the current Covid-19 pandemic which we are currently facing, we are unable to provide any assurances that your patient will be able to travel into or out of the UK if he does not reside in the UK.
Please understand that even with sufficient tumor tissue, there is no guarantee that: (a) your patient would be eligible to enter the UK Specials Program due to changes in his medical condition that might be present at the time he is evaluated for entry into the Program, or (b) the vaccine can be manufactured - we need both sufficient tumor tissue to make a tumor lysate and sufficient dendritic cells to manufacture the vaccine. It is a two-step process that is variable based upon each individual patient. The vaccine is manufactured in such a way that the tissue's antigens are used to "educate" the dendritic cells and millions of those educated dendritic cells become the vaccine. Once injected, the vaccine serves to initiate an immune response against the cancer by recognizing those tumor antigens.
MANUFACTURING
Tumor lysate production
Once we have viable tumor tissue, the first stage of processing is extracting the protein antigen/biomarkers from the tissue to create a tumor lysate. Once that is done the product is sent for quality control testing (a total of 10+ days). If there are any quality control issues, the tumor cell protein lysate may not be released.
Once the lysate has been manufactured, it will be held in frozen storage.
ADCV production
The second stage of processing begins with Salim undergoing a specialized blood draw called a leukapheresis.
This process extracts the monocytes which are the precursors to the dendritic cells and which, in the vaccine manufacturing process, become "educated" to recognize the tumor’s biomarkers and initiate the immune response. The educated dendritic cells are multiplied many times over in order to produce the vaccine. In order to manufacture an ADCV, both sufficient tumor tissue and blood product must be available.
Steroid medication can affect blood volume and the quality of the monocytes available at the time of the leukapheresis. Therefore, steroid levels will be taken into consideration prior to scheduling a leukapheresis blood draw.
The blood cells obtained from the leukapheresis procedure must be used in the vaccine manufacturing process within 20 hours so this procedure must be done in the UK. The availability of leukapheresis appointment slots is extremely limited although we are using several different apheresis centers throughout the UK. Therefore, it is conceivable that your patient might need to wait several weeks until one becomes available.
This stage of processing takes 8 days. Once the ADCV has been manufactured it is sent for quality control testing and final regulatory release, which takes an additional 4 + weeks. The vaccine may not be released if there are any issues with the results of the quality control testing.
Once manufactured, the vaccine is frozen in individual dosage vials and place in a liquid nitrogen freezer until it is ready to be administered.
ADMINISTRATION
Schedule of ADCV Doses
The vaccine doses are administered in three phases:
The Induction Phase initiates the immune response – three separate doses are given by intradermal injection in the upper arm. These doses are usually administered during Month 1 at days 0, 10 and 20.
The Booster Phase enables the immune system to continue its heightened response. These three additional doses are administered during the first year at Months 2, 4, and 8.
After the first year, during the Maintenance Phase, one additional dose is given at Month 12 and then every 6 months until the vaccine supply is depleted.
COSTS AND FEES
The ADCV is a labor-intensive, custom-made cancer immunotherapy vaccine based on the patient’s tumor’s biomarkers and dendritic cells. This ADCV is manufactured by highly trained laboratory technicians in a specialized cGMP cleanroom designed for sophisticated biotech and pharmaceutical manufacturing. The ADCV manufacturing process takes time and extraordinary expertise. The technicians are working with individual patient cells and, as a result, each vaccine is unique.
Please see attached Payment Information form for Autologous Dendritic Cell Vaccine (ADCV).
IN CONCLUSION
I know this is a considerable amount of information and if you have any additional questions, please feel free to contact me. I also want to repeat an important and necessary caveat – Northwest’s ADCV is a treatment option that is given in addition to a standard of care treatment regimen. Although the earlier clinical trials have produced significant data with regards to delayed recurrence and extended life expectancy, Northwest’s ADCV is not considered a cure for GBM.
If your patient is still interested in participating in the UK Specials Program the first step would be for you to find out if excess tumor tissue has been frozen without any preservatives, chemicals or paraffin and how much is available.
Once we are able to confirm that there is sufficient viable tissue, we will start moving forward with a referral to a UK physician you to contact to schedule the medical evaluation to determine your patient’s eligibility to enter the Program. In addition, we will contact the manufacturing lab so they can work with you to arrange transport of your patient’s tumor tissue.
In the meantime, we hope you have been able to maintain your health and vigor over this very difficult past year.
Again, please feel free to contact me with any questions you may have about the ADCV vaccine manufacturing process or any other aspect of the UK Specials Program.
"
"
BACKGROUND
Northwest Biotherapeutics conducted a DCVax -L Phase III clinical trial for adult patients between 18 and 70 years old who had been newly diagnosed with GBM. Trial participants met a number of specific inclusion criteria and had surgery at one of the 81 participating trial sites and met a number of other specific criteria to be accepted into the clinical trial. The clinical trial has completed its cohort (331 patients) in 2015 and has reached data lock.
The drug that is available on a very limited compassionate use / private pay for manufacture basis under the UK Specials regulation is an Autologous Dendritic Cell Vaccine (ADCV) that is manufactured from frozen tissue in the same manner as DCVax-L. The name for the drug that is manufactured under the UK Specials Program is ADCV to avoid confusion with the drug (DCVax-L) that was used in the clinical trial.
Northwest’s vaccine has been made available under the Specials regulation in the UK - this regulation permits patients to receive an experimental drug outside of a clinical trial. Unfortunately, the vaccine is not covered by the UK National Health Service (NHS) or private healthcare insurance.
REQUIREMENTS
In order to manufacture the ADCV, sufficient frozen, viable tumor tissue must be available to extract the tumor antigens/biomarkers to create the tumor cell protein lysate, the first step in manufacturing the vaccine.
Several grams of frozen tumor tissue are required, although it is sometimes possible to use less tissue in certain circumstances. The tissue should be stored without chemicals, preservatives (such as formalin) or paraffin. It needs to be “flash frozen” in a sterile container/cryovial and stored at –70 degrees C or colder. Unfortunately, tumor banks and pathology departments frequently use paraffin or other preservatives that render the tissue unusable for the ADCV process.
It is important to note that the tumor tissue used in the manufacturing of the ADCV must have been stored as excess diagnostic tissue that was not required for primary diagnostic purposes.
CONSIDERATIONS
Some surgeons use Gliadel wafers. If Gliadel wafers were used then an ADCV is not a treatment option because the chemo leaching from the wafer will also kill immune cells which enter the tumor cavity to fight residual tumor cells.
We will not be able to use the tissue of patients that tests positive for infectious disease such as Hepatitis, HIV, Syphilis, and the like. Before tumor tissue can be shipped to the UK, we will need a set of virology tests and to execute several transfer agreements with the storage bank.
The regulatory structure under which the UK Specials Program operates requires that all of the vaccine injections occur in the UK under the supervision of a UK physician participating in the Program.
When the time comes, your patient will be referred to a physician participating in the Specials Program and evaluated as to his medical eligibility to participate in the Program. If he is deemed medically eligible and is enrolled, he will need to be able to travel to the clinic in the UK to undergo a leukapheresis blood draw and all the vaccine must be administered in the London clinic (six doses injected in the upper arm, similar to a flu shot, are given in the first year).
The UK Specials Program is the only access point for Northwest’s ADCV vaccine. I'm afraid there is no regulatory provision for the vaccine to be administered anywhere else. Again, given the current Covid-19 pandemic which we are currently facing, we are unable to provide any assurances that your patient will be able to travel into or out of the UK if he does not reside in the UK.
Please understand that even with sufficient tumor tissue, there is no guarantee that: (a) your patient would be eligible to enter the UK Specials Program due to changes in his medical condition that might be present at the time he is evaluated for entry into the Program, or (b) the vaccine can be manufactured - we need both sufficient tumor tissue to make a tumor lysate and sufficient dendritic cells to manufacture the vaccine. It is a two-step process that is variable based upon each individual patient. The vaccine is manufactured in such a way that the tissue's antigens are used to "educate" the dendritic cells and millions of those educated dendritic cells become the vaccine. Once injected, the vaccine serves to initiate an immune response against the cancer by recognizing those tumor antigens.
MANUFACTURING
Tumor lysate production
Once we have viable tumor tissue, the first stage of processing is extracting the protein antigen/biomarkers from the tissue to create a tumor lysate. Once that is done the product is sent for quality control testing (a total of 10+ days). If there are any quality control issues, the tumor cell protein lysate may not be released.
Once the lysate has been manufactured, it will be held in frozen storage.
ADCV production
The second stage of processing begins with Salim undergoing a specialized blood draw called a leukapheresis.
This process extracts the monocytes which are the precursors to the dendritic cells and which, in the vaccine manufacturing process, become "educated" to recognize the tumor’s biomarkers and initiate the immune response. The educated dendritic cells are multiplied many times over in order to produce the vaccine. In order to manufacture an ADCV, both sufficient tumor tissue and blood product must be available.
Steroid medication can affect blood volume and the quality of the monocytes available at the time of the leukapheresis. Therefore, steroid levels will be taken into consideration prior to scheduling a leukapheresis blood draw.
The blood cells obtained from the leukapheresis procedure must be used in the vaccine manufacturing process within 20 hours so this procedure must be done in the UK. The availability of leukapheresis appointment slots is extremely limited although we are using several different apheresis centers throughout the UK. Therefore, it is conceivable that your patient might need to wait several weeks until one becomes available.
This stage of processing takes 8 days. Once the ADCV has been manufactured it is sent for quality control testing and final regulatory release, which takes an additional 4 + weeks. The vaccine may not be released if there are any issues with the results of the quality control testing.
Once manufactured, the vaccine is frozen in individual dosage vials and place in a liquid nitrogen freezer until it is ready to be administered.
ADMINISTRATION
Schedule of ADCV Doses
The vaccine doses are administered in three phases:
The Induction Phase initiates the immune response – three separate doses are given by intradermal injection in the upper arm. These doses are usually administered during Month 1 at days 0, 10 and 20.
The Booster Phase enables the immune system to continue its heightened response. These three additional doses are administered during the first year at Months 2, 4, and 8.
After the first year, during the Maintenance Phase, one additional dose is given at Month 12 and then every 6 months until the vaccine supply is depleted.
COSTS AND FEES
The ADCV is a labor-intensive, custom-made cancer immunotherapy vaccine based on the patient’s tumor’s biomarkers and dendritic cells. This ADCV is manufactured by highly trained laboratory technicians in a specialized cGMP cleanroom designed for sophisticated biotech and pharmaceutical manufacturing. The ADCV manufacturing process takes time and extraordinary expertise. The technicians are working with individual patient cells and, as a result, each vaccine is unique.
Please see attached Payment Information form for Autologous Dendritic Cell Vaccine (ADCV).
IN CONCLUSION
I know this is a considerable amount of information and if you have any additional questions, please feel free to contact me. I also want to repeat an important and necessary caveat – Northwest’s ADCV is a treatment option that is given in addition to a standard of care treatment regimen. Although the earlier clinical trials have produced significant data with regards to delayed recurrence and extended life expectancy, Northwest’s ADCV is not considered a cure for GBM.
If your patient is still interested in participating in the UK Specials Program the first step would be for you to find out if excess tumor tissue has been frozen without any preservatives, chemicals or paraffin and how much is available.
Once we are able to confirm that there is sufficient viable tissue, we will start moving forward with a referral to a UK physician you to contact to schedule the medical evaluation to determine your patient’s eligibility to enter the Program. In addition, we will contact the manufacturing lab so they can work with you to arrange transport of your patient’s tumor tissue.
In the meantime, we hope you have been able to maintain your health and vigor over this very difficult past year.
Again, please feel free to contact me with any questions you may have about the ADCV vaccine manufacturing process or any other aspect of the UK Specials Program.
"
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