The MHRA Papers - Part 2

We have some questions, but there is no formal obligation to reply

We continue reviewing the minutes of the three meetings of the MHRA’s ​​Commission On Human Medicines (CHM) COVID-19 Vaccines Benefit Risk Expert Working Group, which took place between 28 October and 18 November 2020.

During the first meeting, the EWG reviewed the non-clinical and clinical evidence from trial BNT162b2 (Pfizer Biontech). As you may recall from our series on Comirnaty, manufacturers started running two studies in April 2020.

Exploring regulatory data sets of the Comirnaty vaccine - 2

The first is BNT16201, divided into b1 and b2—abbreviated to BNT162b1 (120 participants) and BNT 162b2 (96). The trial is a phase 1 dose-ranging study that was run in Germany.

The first odd thing we noticed is the following statement: “3.2 The EWG agreed that the pharmacokinetics posed no particular concerns.” This is inconsistent with the statement immediately following:

Oddly, parenteral vaccine content stays mainly at the injection site, eliciting a reaction from our immune system (as in the job description). In this case, the stuff went just about everywhere in internal rats’ organs, including the central nervous system and ovaries.

We reported that the Japanese regulator PMDA was also not particularly concerned about the distribution of Comirnaty in rats but considered the product a powerful drug, not a biological one.

Exploring regulatory data sets of the Comirnaty vaccine - 9a

In the 10th of November meeting, Astra Zeneca's revision of its statistical analysis plan was mentioned, but the session was otherwise unremarkable.

The 18th of November meeting provided some very troubling (to us) points summarised below (our emphasis)

‘The EWG heard there would be a lower degree of risk associated with the ‘clinical trial product’ due to the availability of safety data.’

Yet:

‘The EWG noted the sparse data and information on flow, batch testing, protocols, and full roll-out details.’

and

‘The EWG also noted that the duration of available follow-up data could be insufficient to capture the development of adverse events.’

‘The EWG asked if the vaccine's lipid nanoparticle element possesses any adjuvant properties other than innate adjuvant activity.’

The EWG also noted that lymphopenia was reported in the vaccine in the phase I trial.

Then we have a surprising statement:

‘The EWG asked if the company are required to respond to the 36 questions posed by the MHRA.’

We only managed 15 on the pharmacokinetics of Comirnaty.

Exploring regulatory data sets of the Comirnaty vaccine - 9e

However, the MHRA confirmed that while there is no formal obligation to reply, key issues such as sufficient data/detail on product stability, batch qualification, and adventitious agents, e.g., TSE status, will be required before any form of authorisation is awarded.

The following posts in this series do not answer the 36 questions. Indeed, they vanished, as no one in the EWG was tasked with following up with them. To discover what happened to the 36 secret squirrel questions, an FOI request might be required.

The manufacturers were not formally required to answer them. How can that be? How can you make impartial decisions on behalf of millions of people if you cannot ask questions, or rather, if you have no power to enforce answers?

The minutes contained statements that rang our clinical alarm bells, such as the mention of lymphopenia and the manufacturer's dismissal of it as an issue.

The EWG noted that lymphopenia was reported in the vaccine group in the phase I trial. The company confirmed that the vaccine’s mechanism of action is expected to induce lymphopenia, and all events in phase I were transient and resolved entirely.

Yet, Testing for lymphopenia was not conducted in phase II/III of the trial.

‘The EWG noted the potential signal of lymphadenopathy in the clinical trial data: 44 events in the vaccine arm related to upper limb lymph nodes compared to 4 in the placebo group.’

‘The EWG also noted a potential linkage to the 6 cases of appendicitis in the vaccine arm compared to one in the placebo group, which should be explored further and monitored.’

Identifying the lymphopenia issue should have been a wake-up call, as lymphocytes are our guardians against viral disease. Suppose the vaccine induces lymphopenia and was not followed in the phase II/III mega trial. In that case, the registration process should have stopped, emergency or otherwise, as the benefit-risk ratio assessment would have been skewed.

So we went to look again at the exclusion criteria for the largest study, C4591001, and this is what we found:

The exclusion of anyone with possible active disease (even if asymptomatic) and anyone with the possibility of a weak or non-existent immune system is now explained. If you are infected or at significant risk of it and vaccinated, you have little immunity to fight SARS-CoV-2.

Remember, all these transactions were secret, although we all, dear readers, were the targets.

This post was written by two old geezers who have difficulty believing what they have been reading.