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Homepage – Forum Forums Research, Clinical Trials, and New Treatments FDA approves Ferring’s Adstiladrin for BCG Unresponsive NMIBC

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    On December 16, FDA approved nadofaragene firadenovec-vncg (Adstiladrin), a nonreplicating adenoviral vector–based gene therapy developed by Ferring Pharmaceutical Inc. of Switzerland of her Canadian headquarter is located in North York, Ontario.  Adstiladrin(R) is for BCG Unresponsive  High risk Non-Muscle  Invasive Bladder Cancer (NMIBC).   High Risk NMIBC includes Ta/T1HG and CIS.  BCG Unresponsive means those who had recurrence after adequate BCG treatment.  5+ weeks induction + 2+weeks maintenance BCG treatment.   Note that for T1HG, patient’s bladder is checked after the induction course and if it has recurrence it is considered BCG Unresponsive. In case of CIS, it is considered BCG Unresponsive if there is recurrence after the induction + at least one 2-3 weekly maintenance treatment.

    Below is the summary of the result of the clinical trial (157 patients) which led to the FDA approval

    Overall, 51% of enrolled patients receiving Adstiladrin achieved a complete response. The median duration of response was 9.7 months. About 46% of responding patients remained in complete response for at least 1 year.

    The most common adverse reactions associated with Adstiladrin included bladder discharge, fatigue, bladder spasm, urinary urgency, hematuria, chills, fever, and painful urination. Individuals who are immunosuppressed or immune-deficient should not come into contact with Ad

    Adstiladrin is administered once every 3 months into the bladder via a urinary catheter.

    Mechanism of Action

    Adstiladrin is a non-replicating adenovirus vector-based gene therapy containing the gene interferon alfa-2b. The vector enters the cells of the bladder wall, releasing the active gene. The internal gene/DNA machinery of the cells “picks up” the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient’s own bladder wall cells into interferon microfactories, enhancing the body’s natural defenses against the cancer.   ** from internet

    Below are my understanding.  I think 80% are correct.

    The agent which kills cancer is high quantities of interferon alfa 2b protein.   Interferon alfa 2b protein had been used in combination with BCG for BCG Unresponsive until MERCK dropped Interferon alfa 2b protein manufacturing business.

    The agent interferon alfa 2b protein is delivered to bladder cancer cells in the form of the gene for interferon alfa protein.  Once it is delivered to a cancer cell, enzymes  in the cell  read the gene and produce interferon alfa 2b protein which invokes our immune system to kill cancer cells.

    The vehicle to deliver high quantity of gene  for interferon alfa 2b protein is adeno virus which was engineeringly modified virus such as for common cold so it will not cause cold, and designed so it infects specifically cancer cells only and not healthy cells.

    Mechanism of Interferon alfa 2b  how it kills cancer cell ** from internet.

    Interferon alfa is a type of medication called a biologic response modifier. It is a type of protein called a cytokine that works to increase the function of various components of the body’s immune system. This protein is normally produced in the body but in small amounts. By increasing the levels of interferon, the immune system gets a kick-start, mounting an attack against the cancer cells, which are seen as foreign invaders. In addition, interferon-alpha is able to interfere with the cancer cell’s ability to divide.


    Hi Joe:

    This sounds promising.  Side effects sound similar to BCG.  My concern would be about how the side effects might be overwhelming if a patient embarks on a regime of this after BCG.  I’m hoping that there is some information about how long to wait after BCG failure before embarking on this. Any knowledge of whether Health Canada will approve it?


    Hi Marysue,

    According to the analysis of Phase 3 clinical trial which led to the approval of Nadofaragene firadenovec – Adstiladrin (R), published in Lancet Oncology in January 2021, side effects are as follows.   I have listed the link of the clinical trial result at the end

    Side effects – note that pre-treatment anticholinergic therapeutic agents on each instillation dosing day to minimise irritative voiding symptoms.

    Of 157 patients, 3 patients discontinued the study because of adverse events

    Grade 1-2  side effects which did not require hospitalization  103 (66%)

    Discharge around the catheter during instillation  39 (25%)

    Fatigue 31(20%)

    Bladder spasm 24 (15%)

    Micturition urgency 22 (14%)

    Chills  18 (12%)

    Dysuria 17 (10%)

    Pyrexia 16 (10%)

    Syncope 0

    Hypertension 2(1%)

    Urinary incontinence 4 (3%)

    Grade 3 – which required hospitalization  6 (4%)

    Bladder spasm 1 (1%)

    Micturition urgency 2 (1%)

    Syncope  1 (1%)

    Hypertension 1 (1%)

    Urinary incontinence 1 (1%)

    The study says most side effects are transient.  Note that patients are treated once every three months


    The start of treatment

    The study says if the recurrence was T1HG, the patient had the second TURBT, and for them, the treatment started 14-60 days after the second TURBT.   If the recurrence is CIS, obvious areas of CIS were fulgurated before beginning study treatment.   So, it sounds like the treatment can start as soon as the lining of bladder looks healed after TURBT or fulguration.

    When will Health Canada approve the drug for the use in Canada?

    I think within a year once the drug manufacturer Ferring applies for it. The sticky point is the price of the drug.  In the US, the manufacture can price the drug any price as she wants.   The price of a new bladder cancer drug costs US $100K-$150K per year of treatment, so the treatment needs two years, the drug costs $200K to $300K a year.  There is an independent organization The Institute for Clinical and Economic Review (ICER) who decides the validity of the price a new drug.  ICER recommended health-benefit price bench mark of  Nadofaragene firadenovec – Adstiladrin (R) is US$ 158,600-$262,000 per year.   I do not know about US, but Canada cannot afford it.   It is much cheaper to offer alternative but inferior treatment such as intravesical gemcitabine or cystectomy.   So, in Canada, there is also an organization called  The Canadian Agency for Drugs and Technologies in Health, or CADTH that provides research and analysis to health decision makings.  CADTH decides what price can be justified.   For example,   Heath Canada approved immunotherapy drug called Avelumab.  Avelumab was approved in January, 2021 as maintenance treatment of advanced bladder cancer after cisplatin based chemotherapy as the first line treatment.  ICER in the US calculated  $278,000 per year as the legitimate pricing.  CADTH in Canada calculated such that at least a price deduction of 83% is necessary for Avelumab to be used in Canada.  I do not know if the manufacture of Avelumab had agreed to 83% deduction or about $50K year pricing for Canada.   I know Avelumab is being administered to patients in Canada, but I do not know if the pricing has been agreed or not.  Often manufacturer of Cancer drugs provides the drug as compassionate use.    Incidentally,  CADTH calculated the cost to Health Canada of providing Avelumab as standard treatment in Canada will add about CDN $300 million to her budget.   So, the availability depends upon the price agreement between Canada and Ferring, the manufacture of Nadofaragene firadenovec – Adstiladrin (R).

 ”    link to the analysis of the clinical trial of Nadofaragene firadenovec – Adstiladrin (R).





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