I correct two lies CDC told ACIP yesterday re Moneypox drug TPOXX and the Jynneos vaccine

3 Drugs that might be used for money pox

1. Brincidofovir. Brincidofovir
is licensed (since 1996) for treatment of smallpox but is not available
in the US stockpile (termed the National Strategic Stockpile) and CDC
is considering obtaining an expanded access IND (a legal permission from
FDA to test/use it in people) so that it could legally be used if
needed. But it could be used off-label, since it is licensed. Why is
CDC jumping through unnecessary hoops? Probably in order to control the
supply, in a similar though not identical manner to what FDA did with
donated hydroxychloroquine.

2. TPOXX, the
controversial drug made by SIGA Technologies. When the Obama
administration first tried to buy this drug, Congress had a fit and the
media helped blow up the deal. From David Willman, writing for the LA Times in 2011:

Over
the last year, the Obama administration has aggressively pushed a
$433-million plan to buy an experimental smallpox drug, despite
uncertainty over whether it is needed or will work.

Senior
officials have taken unusual steps to secure the contract for New
York-based Siga Technologies Inc., whose controlling shareholder is
billionaire Ronald O. Perelman, one of the world’s richest men and a
longtime Democratic Party donor.

When Siga complained
that contracting specialists at the Department of Health and Human
Services were resisting the company’s financial demands, senior
officials replaced the government’s lead negotiator for the deal,
interviews and documents show.

When Siga was in danger of losing its grip on the contract a year ago, the officials blocked other firms from competing…

Negotiations
over the price of the drug and Siga’s profit margin were contentious.
In an internal memo in March, Dr. Richard J. Hatchett, chief medical
officer for HHS’ biodefense preparedness unit, said Siga’s projected
profit at that point was 180%, which he called “outrageous.”

So
the Obama administration simply waited out the media storm, and bought
the drug for $30 million more in 2013. Here is what the NYT said about it in 2013, when the purchase was finalized:

The United States government is buying enough of a new smallpox medicine to treat two million people
in the event of a bioterrorism attack, and took delivery of the first
shipment of it last week. But the purchase has set off a debate about
the lucrative contract, with some experts saying the government is
buying too much of the drug at too high a price.

A
small company, Siga Technologies, developed the drug in recent years.
Whether the $463 million order is a boondoggle or bargain depends on
which expert is talking…

Dr. Henderson and Dr.
Philip Russell, who formerly headed the Walter Reed Army Institute of
Research and served on the advisory panel with him, said they expected
the government to pay much less for an antiviral drug since they cost
little to make and the alternative, vaccines, cost the government $3 a
dose. “If they’re talking $250 a course, they’re a bunch of thieves,”
Dr. Russell said.

Asked how much TPOXX
(Tecovirimat) and 3. Vaccinia Immune Globulin there is in the stockpile,
the CDC’s Dr. Petersen would not answer, only saying there was enough.
He didn’t know that I recalled the NY Times had spilled the beans on the
initial purchase of 2 million courses. How much have they bought
since? Presumably someone decided it would not be in the governments’
best interest for the public to know how much of these unproven products
were purchased from a top Dem donor.

In 2018, FDA gave the drug a license. The NYT explained how this happened:

The
antiviral pill, tecovirimat, also known as Tpoxx, has never been tested
in humans with smallpox because the disease was declared eradicated in
1980, three years after the last known case.

But it was very effective at protecting animals deliberately infected with monkeypox and rabbitpox, two related diseases that can be lethal. It also caused no severe side effects when safety-tested in 359 healthy human volunteers, the F.D.A. said…

The
F.D.A. approval of the drug went to Siga Technologies of Corvallis,
Ore., a private company that developed the medicine under a federal
biomedical defense contract… Research on tecovirimat — originally
designated ST-246 — began at the institute (NIAID) after the 9/11
terrorist attack on the World Trade Center, Dr. Fauci said.

So
the taxpayer paid to develop it, and paid through the nose to buy it,
Fauci-style, no doubt paying royalties back to the NIAID.

Is there a public health emergency?

Dr.
Maldonado asked about the possible designation of a public health
emergency of International Concern by WHO, and how this would impact
CDC.

Yes, WHO had a meeting to discuss this today, said Dr.
Petersen, and CDC participated but he does not know what the result was.
EUAs could eventuate if there are emergency declarations.

Dr.
Maldonado further noted that the presentation (the severity and overall
clinical picture) of moneypox is unexpected for orthopox viruses… and
then asks what to do about children. There have been NO child cases
internationally (excluding Africa?—Nass) said Dr. Rao. She says cases
in Nigeria have been strange too, but I was confused about whether they
were equivalent to those in the west or more like historical cases. Dr.
Petersen agreed. Melinda Wharton (the new exec secretary of the ACIP
as well as having been a member of the FDA’s vaccine advisory committee)
says that recommended PPE for moneypox includes gloves and respirator,
and was not sure if medical providers would be considered at risk after
seeing a patient, particularly if they used no respirator.

Dr. Rao
says she will need to get back to the committee on this; the risk
exposure assessment is being revised, it seems, by CDC.

Dr.
Fryhofer asked about expected adverse events of the proposed drugs.
Cidofovir has renal toxicity and is used with cimetidine in an effort to
prevent that. Brincidofovir has liver and GI toxicity.

TPOXX is “quite safe and well tolerated” says Dr. Petersen.

However, it was only tested in 359 people
in a phase 3 trial, according to the label. At least one experienced
EKG (cardiac) changes, and at least one had a drop in their blood count.
Another had palpable purpura, which can be quite serious, usually the
result of autoimmune vasculitis. Facial swelling suggests anaphylaxis.
That is a rate of more than 1% experiencing serious adverse events after only taking the drug for 14 days or less. This was the first lie I caught him on.

Regarding
how moneypox spreads, Dr. Rao says “the cases we are aware of are due
to skin contact or towels, bedding”. 99% of cases recently were
attributed to gay males, I read elsewhere. Dr. Long persists with her
original question, asking whether the general US population should be
worried about normal casual contacts, like going to the grocery store?
Dr. Rao hedges, saying that Americans don’t need to worry about this,
and at first said it seems to require “pretty intimate contact.” But
then she qualified it, noting, “The risk to the general public at this time is still very low.”

Dr.
Rao is asked to comment on a CDC statement that the virus is
transmitted through respiratory secretions. She says it is due to
saliva, respiratory droplets, implying no airborne spread.

Dr.
Sanchez asks how severe the disease actually is. The breifer said
hospitalizations have been for pain control, like proctitis. 197
courses of TPOXX have been distributed and 8 cases
have received the drug…but none have gotten it iv, so I am again
confused by the answer. I think what was meant is that no one has
received immune globulin (an iv drug) yet. Dr. Petersen admits cases have been mild.

Dr. Grace Lee says she was exhausted, they have been meeting so much to provide into to the public, and it is time to adjourn.

__________________

My computer saves the day

I
am so glad my computer started broadcasting the end of the ACIP meeting when I finally
got to my destination—as soon as it connected to wifi and before I had
even plugged it in, it began talking to me. I heard the second part of
Dr. Brent Petersen’s presentation, and the questions, described above.

Why
am I glad? Because I caught Dr. Petersen lying to the ACIP. Twice.
He claimed that there were 5.7. cases of myocarditis per 1,000
recipients due to ACAM2000 smallpox vaccine [true], but none from Jynneos.

This
reminded me that before I began live-blogging some of the meetings,
years ago, I had discovered from reading the abbreviated ACIP meeting minutes [who
knows how accurate they are?] that the CDC briefers were lying to the
ACIP about anthrax vaccine. It seems they leave nothing to chance in order to get their desired vaccine approvals.

If you read my post on Monkeypox published June 22, you would know that I looked over the 200 page FDA licensure review of the Jynneos smallpox-monkeypox vaccine. That is where I discovered that 2 studies of Jynneos
found that 11% in one and and 18% of recipients in the other had
developed elevated levels of cardiac enzymes (troponin). This implies
heart muscle damage of some kind. It was not studied further, and the
reviewers admitted they did not know whether myocarditis was caused by
the Jynneos vaccine, or not. And that they would need to perform future surveillance to find out.

I
wonder why Dr. Petersen, one of CDC’s monkeypox leads, brazenly lied to
the committee about this? Was he so instructed? Or was he incompetent
and ignorant? We can probably assume that CDC’s employees know on
which side their bread is buttered. Since CDC has made the decision
that Jynneos is to be used against monkeypox, despite its apparently awful risk-benefit ratio (see my monkeypox article) I imagine all its employees will be sticking to this story.

__________________

Here is what the Jynneos label
(aka package insert, the legal document explaining the studies that led to licensure) has to
say. 1.3% of recipients had a cardiac adverse event of special
interest, and 2.1% if they had previously been vaccinated for smallpox. That seems pretty serious, and it seems like a very high rate:
1 in 75. From the label:

Cardiac AESIs were reported to occur in 1.3% (95/7,093) of JYNNEOS recipients and 0.2% (3/1,206)
of placebo recipients who were smallpox vaccine-naïve. Cardiac AESIs were reported to occur in
2.1% (16/766) of JYNNEOS recipients who were smallpox vaccine-experienced. The higher
proportion of JYNNEOS recipients who experienced cardiac AESIs was driven by 28 cases of
asymptomatic post-vaccination elevation of troponin-I in two studies: Study 5, which enrolled
482 HIV-infected subjects and 97 healthy subjects, and Study 6, which enrolled 350 subjects with
atopic dermatitis and 282 healthy subjects. An additional 127 cases of asymptomatic post-vaccination
elevation of troponin-I above the upper limit of normal but not above 2 times the upper limit of normal
were documented in JYNNEOS recipients throughout the clinical development program, 124 of which
occurred in Study 5 and Study 6. Proportions of subjects with troponin-I elevations were similar
between healthy and HIV-infected subjects in Study 5 and between healthy and atopic dermatitis
subjects in Study 6. A different troponin assay was used in these two studies compared to the other
studies, and these two studies had no placebo controls. The clinical significance of these
asymptomatic post-vaccination elevations of troponin-I is unknown.
Among the cardiac AESIs reported, 6 cases (0.08%) were considered to be causally related to
JYNNEOS vaccination and included tachycardia, electrocardiogram T wave inversion,
electrocardiogram abnormal, electrocardiogram ST segment elevation, electrocardiogram T wave
abnormal, and palpitations.
None of the cardiac AESIs considered causally related to study vaccination were considered serious.