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.