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- Date of the document : December 1 – 2020
- To : European Medicines Agency – Committee for human medicinal products (CHMP) COVID-19 EMA pandemic Task Force (COVID-ETF)
- From : Doctor Wolfgang Wodarg (physician, doctor and Politician) – Dr Michael Yeadon (former VP of PFIZER)
PETITION/MOTION FOR ADMINISTRATIVE/REGULATORY ACTION REGARDING CONFIRMATION OF EFFICACY END POINTS AND USE OF DATA IN CONNECTION WITH THE FOLLOWING CLINICAL TRIAL(S):
PHASE III – EUDRACT NUMBER: 2020-002641-42 SPONSOR PROTOCOL NUMBER: C4591001
BIONTECH SE (SOCIETAS EUROPAEA), AN DER GOLDGRUBE 12, 55131 MAINZ, GERMANY
AND ANY OTHER ONGOING CLINICAL TRIALS OF VACCINE CANDIDATES DESIGNED TO STOP TRANSMISSION OF THE VIRUS FROM THE VACCINE RECIPIENT TO OTHERS AND/OR TO PREVENT COVID-19 OR MITIGATE SYMPTOMS OF COVID-19 FOR WHICH PCR RESULTS ARE THE PRIMARY EVIDENCE OF INFECTION
ADMINISTRATIVE/REGULATORY STAY OF ACTION
This petition for a stay of action is submitted by the undersigned (“Petitioner” or “Lead Petitioner”) to request the EMA a) stay the Phase III clinical trial(s) of BNT162b (EudraCT Number 2020-002641-42) in the EU (current protocol country: Germany) until study design is amended to conform with the requests in the “Action Requested” section (B.) below; and b) stay all other clinical trials of vaccine candidates designed to stop transmission of the virus from the December 1, 2020 vaccine recipient to others and/or prevent or mitigate symptoms of COVID-19 for which PCR results are the primary evidence of infection. Because of the compelling need to ensure the safety and efficacy of any COVID-19 vaccine licensed by the EMA (and/or the German Paul-Ehrlich-Institut), and to allow Petitioner the opportunity to seek appropriate emergency judicial relief should the EMA deny its Petition, Petitioner respectfully requests that EMA act on the instant Petition immediately.
A. DECISIONS INVOLVED
I. Approval of the trial design and/or decision not to challenge the trial design for Phase III
of BNT162 (EudraCT number 2020-002641-42)
II. Approval of the trial plan and/or decision not to challenge the trial plan of all other candidate vaccine clinical trials designed to stop transmission of virus from the vaccine recipient to others and/or to prevent or mitigate the symptoms of COVID-19 for which PCR results are the primary evidence of infection.
B. ACTION REQUIRED
I. Suspend the Phase III trial of BNT162 in the protocol country, Germany, and in any other protocol country.
EU protocol countries (if applicable) until the study plan is amended to include it : Before an Emergency Authorization/Conditional Authorization and/or an Unrestricted Authorization is issued for the Pfizer/BioNTech vaccine, all “endpoints” or COVID-19 cases used to determine vaccine efficacy in Phase 3 or 2/3 trials must have their infection status confirmed by appropriate Sanger sequencing (as described in Section C. III. below), taking into account (a) the high cycle thresholds used in some trials; and (b) design flaws in some RT-qPCR tests identical to or modeled after what is sometimes referred to as the “Drosten-Test”.
II. Stay the clinical trials of all vaccine candidates designed to stop transmission of the virus from the vaccine recipient to others and/or to prevent or mitigate symptoms of COVID-19 for which PCR results are the primary evidence of infection until study design is amended to provide that: Before an Emergency Authorization/Conditional Approval and/or Unrestricted Authorization is issued for vaccine designed to stop transmission of the virus from the vaccine recipient to others and/or to prevent or mitigate symptoms of COVID-19, all “endpoints” or COVID-19 cases used to determine vaccine efficacy should have their infection status confirmed by appropriate Sanger sequencing (as described in section B. III. below), given a) the high cycle thresholds used in some trials; and b) design flaws of certain RT-qPCR tests identical to or modeled after what is sometimes called the “Drosten-Test”.
III. High cycle thresholds, or Ct values, in RT-qPCR test results have been widely acknowledged to lead to false positives. Also, a group of scientists and researchers have recently called for a retraction of the paper that describes the so called “Drosten-Test” (sometimes also being referred to as the “Corman-Drosten protocol” – a specific RT-qPCR assay described by Corman,Victor M., Drosten, Christian and others in “Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR.” Euro Surveillance 2020;25(3):pii=2000045. https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045). All RT-qPCR-positive test results used to categorize patient as “COVID-19 cases” in the trials and used to qualify the trial’s endpoints should be verified by Sanger sequencing to confirm that the tested samples in fact contain a unique SARS-CoV-2 genomic RNA. Congruent with FDA and EMA requirements for a confirmed diagnosis of human papillomavirus (HPV) using PCR, the sequencing electropherogram must show a minimum of 100 contiguous bases matching the reference sequence with an Expected Value (E Value) <10-30 for the specific SARS-CoV-2 gene sequence based on a BLAST search of the GenBank database (aka NCBI Nucleotide database).
C. STATEMENT OF GROUNDS
I. As detailed herein, (i) without the requested stay, the Petitioner and many EU residents/citizens will suffer irreparable harm, (ii) the request is not frivolous and is being pursued in good faith, (iii) the request demonstrates sound public policy, and (iv) the public interest favors granting a stay.
II. Petitioner deems the current study designs for the Phase II/III trials of BNT162b (“the Pfizer/BioNTech trial”) to be inadequate to accurately assess efficacy. Petitioner also deems the designs of clinical trials of vaccine candidates designed to stop transmission of the virus from the vaccine recipient to others and/or to prevent or mitigate symptoms of COVID-19 for which PCR results are the primary evidence of infection to be inadequate to accurately assess efficacy.
III. Petitioner and the public will suffer irreparable harm if the actions requested herein are not granted, because once the EMA (and other appropriate bodies in the various EU member states) approves the COVID-19 vaccines in question, both governments of EU member states and employers in the EU are most likely going to recommend them for widespread use. If the assignment of cases and non-cases during the course of the trials is not accurate, the vaccines will not have been properly tested. If the vaccines are not properly tested, important public policy decisions regarding its use will be based on misleading evidence. The medical and economic consequences to EU member states and their residents/citizens could hardly be higher.
IV. Furthermore, if the vaccines are approved without an appropriate and accurate review of efficacy, then any potential acceptance or mandate of these vaccines is likely to be based on inaccurate evidence regarding the vaccine, namely that it will stop transmission of the virus from the vaccine recipient to others and/or that it will reduce COVID-19 disease and deaths. The Pfizer/BioNTech trial protocol and other trial protocols are currently not designed to determine whether either of those objectives can be met; and even if it was, if cases cannot be reliably identified, neither objective could be reliably met.
V. The public interest also weighs strongly in favor of the requested relief because improving the accurate determination of primary endpoints (i) will comport with the best scientific practices, (ii) increase public confidence in the efficacy of a product likely to be mandated or intended for widespread use, and (iii) not doing so will have the opposite result and create uncertainties regarding the efficacy of and need for the COVID-19 vaccines.
VI. Petitioner hereby incorporates the grounds, facts, arguments and opinions stated in the “PETITION FOR ADMINISTRATIVE ACTION REGARDING CONFIRMATION OF EFFICACY END POINTS OF THE PHASE III CLINICAL TRIALS OF COVID-19 VACCINES” which has been submitted to the FDA by Dr. Sin Hang Lee via electronic filing on November 25, 2020 (Exhibit A – Docket No. FDA-2020-P-2225). Exhibit A attached hereto shall be incorporated herein and shall be understood to be a part hereof as though included in the body of this petition.
VII. Petitioner hereby also incorporates the grounds, facts, arguments and opinions stated in the external peer review of the “Drosten-Test” (Exhibit B). Design flaws of certain RT-qPCR tests that are identical to or modeled after what is sometimes called the “Drosten-Test” can lead to false-positive results in trials designed such that PCR results are the primary evidence of infection. Exhibit B attached hereto shall be incorporated herein and shall be understood to be a part hereof as though included in the body of this petition.
VIII.For a vaccine to work, our immune system needs to be stimulated to produce a neutralizing antibody, as opposed to a non-neutralizing antibody. A neutralizing antibody is one that can recognize and bind to some region (‘epitope’) of the virus, and that subsequently results in the virus either not entering or replicating in your cells. A non-neutralizing antibody is one that can bind to the virus, but for some reason, the antibody fails to neutralize the infectivity of the virus. In some viruses, if a person harbors a non-neutralizing antibody to the virus, a subsequent infection by the virus can cause that person to elicit a more severe reaction to the virus due to the presence of the non-neutralizing antibody. This is not true for all viruses, only particular ones. This is called Antibody Dependent Enhancement (ADE), and is a common problem with Dengue Virus, Ebola Virus, HIV, RSV, and the family of coronaviruses. In fact, this problem of ADE is a major reason why many previous vaccine trials for other coronaviruses failed. Major safety concerns were observed in animal models. If ADE occurs in an individual, their response to the virus can be worse than their response if they had never developed an antibody in the first place. This can cause a hyperinflammatory response, a cytokine storm, and a generally dysregulation of the immune system that allows the virus to cause more damage to our lungs and other organs of our body. In addition, new cell types throughout our body are now susceptible to viral infection due to the additional viral entry pathway. There are many studies that demonstrate that ADE is a persistent problem with coronaviruses in general, and in particular, with SARS-related viruses. ADE has proven to be a serious challenge with coronavirus vaccines, and this is the primary reason many of such vaccines have failed in early in-vitro or animal trials. For example, rhesus macaques who were vaccinated with the Spike protein of the SARS-CoV virus demonstrated severe acute lung injury when challenged with SARS-CoV, while monkeys who were not vaccinated did not. Similarly, mice who were immunized with one of four different SARS-CoV vaccines showed histopathological changes in the lungs with eosinophil infiltration after being challenged with SARS-CoV virus.
IX. There are some concerning issues with the trial designs, spelled out by Dr. Peter Doshi in the British Medical Journal. Dr. Doshi focuses on the two biggest issues. First, none of the leading vaccine candidate trials is designed to test if the vaccine can reduce severe COVID-19 symptoms, defined as: hospital admissions, ICU or death. And, second, the trials are not designed to test if the vaccine can interrupt transmission (https://www.bmj.com/content/bmj/371/bmj.m4037.full.pdf). If neither of these conditions is met, the vaccine in essence performs like a therapeutic drug, except a vaccine would be taken prophylactically, even by the perfectly healthy, and more than likely carries a higher risk of injury than a therapeutic drug. If this were to be true, then therapeutic drugs would be superior to any COVID vaccine.
X. In the Pfizer/BioNTech mRNA vaccine candidate, polyethylene glycol (PEG) is found in the fatty lipid nanoparticle coating around the mRNA. Seventy percent of people make antibodies to PEG and most do not know it, creating a concerning situation where many could have allergic, potentially deadly, reactions to a PEG-containing vaccine. PEG antibodies may also reduce vaccine effectiveness. Pfizer/BioNTech is also inserting an ingredient derived from a marine invertebrate, mNeonGreen, into its vaccine. The ingredient has bioluminescent qualities, making it attractive for medical imaging purposes, but it is unclear why an injected vaccine would need to have that quality. mNeonGreen has unknown antigenicity.
XI. Several vaccine candidates are expected to induce the formation of humoral antibodies against spike proteins of SARS-CoV-2. Syncytin-1 (see Gallaher, B., “Response to nCoV2019 Against Backdrop of Endogenous Retroviruses” – http://virological.org/t/response-to-ncov2019- against-backdrop-of-endogenous-retroviruses/396), which is derived from human endogenous retroviruses (HERV) and is responsible for the development of a placenta in mammals and humans and is therefore an essential prerequisite for a successful pregnancy, is also found in homologous form in the spike proteins of SARS viruses. There is no indication whether antibodies against spike proteins of SARS viruses would also act like anti-Syncytin-1 antibodies. However, if this were to be the case this would then also prevent the formation of a placenta which would result in vaccinated women essentially becoming infertile. To my knowledge, Pfizer/BioNTech has yet to release any samples of written materials provided to patients, so it is unclear what, if any, information regarding (potential) fertility-specific risks caused by antibodies is included.According to section 10.4.2 of the Pfizer/BioNTech trial protocol, a woman of childbearing potential (WOCBP) is eligible to participate if she is not pregnant or breastfeeding, and is using an acceptable contraceptive method as described in the trial protocol during the intervention period (for a minimum of 28 days after the last dose of study intervention).This means that it could take a relatively long time before a noticeable number of cases of post- vaccination infertility could be observed.
XII. It appears that Pfizer/BioNTech have not yet released any samples of written materials provided to patients, so it is unclear what, if any, instructions/information patients/subjects were given regarding ADE and PEG-related issues and (potential) fertility- or pregnancy-specific issues.
D. STAY URGENTLY REQUIRED
I. Petitioner any many EU residents/citizens will suffer irreparable harm because once the EMA approves the COVID- 19 vaccine(s) in question, both governments of EU member states and employers in the EU are most likely going to recommend them for widespread use, and hence without the EMA assuring proper safety trials of the vaccines now, the Petitioner and others will not have the opportunity to object to receiving the vaccine based on deficient clinical trials later.
II. Furthermore, if the vaccines are licensed without an appropriate efficacy review and without improving the accurate determination of primary endpoints, then any potential acceptance or mandate of these vaccines are likely to be based on inaccurate beliefs and data about the vaccines, namely that they will or might stop transmission of the virus from the vaccine recipient to others and/or that it will reduce severe COVID-19 disease and deaths. The trial protocols in question are not currently properly designed to determine whether either of those objectives can be met.
III. This petition is also not frivolous and is being pursued in good faith as it seeks to increase the scientific integrity and reliability of the trials of the COVID-19 vaccines.
IV. Finally, the public interest also weighs strongly in favor of the requested relief because improving the accurate determination of primary endpoints (i) will comport with the best scientific practices, (ii) increase public confidence in the efficacy of a vaccine expected to be mandated or strongly recommended for widespread use, and (iii) not doing so will have the opposite result in that it will create uncertainties regarding the efficacy of and need for the COVID-19 vaccines.
V. The Petitioner therefore respectfully urges that this request be granted forthwith. Respectfully submitted on my behalf and on behalf of Co-Petitioner Dr. Michael Yeadon:
Dr. med. Wolfgang Wodarg
Exhibit A Exhibit B