Tag: fda advisory committee

FDA Advisory Committee Meeting Today on Pfizer COVID-19 Vaccine for Children Ages 5-11

The meeting will go from 7:30 AM-5:00 PM, ET, and the Voting Question will be:

“Based on the totality of scientific evidence available, do the benefits of the Pfizer BioNTech COVID-19 Vaccine when administered as a 2-dose series (10 µg each dose, 3 weeks apart) outweigh its risks for use in children 5-11 years of age.” Please vote yes or no.

This is about extending the EUA for the Pfizer vaccine for this age group. It would be administered as a 2-dose vaccine, 10 micrograms each, 3 weeks apart. COVID-19 causes substantial morbidity and mortality in this age group.

Unlike the other recent FDA presentations I’ve seen, today there was a reminder that, in view of the polarized opinions pro and con about this question, all participants should do their best to observe the utmost civility at all times during the proceedings.

Dr. Fiona Havers presented the epidemiology of COVID-19 in this age group. It showed increasing infections and severe disease and hospitalization rates, which were higher among African American and other minority children than among white. Secondary transmission can and does occur among children and adults. See the slides.

Dr. Matthew Oster’s presentation on mRNA vaccine associated myocarditis showed that myocarditis is a rare but important adverse event following COVID-19 vaccination. See the slides.

Break.

The Pfizer presentation highlighted safety and efficacy data for the vaccine. See Dr. Gruber’s briefing document and slides. The FDA presentation by Dr. Leslie Ball, MD, summarized the immunogenicity and safety data (see summary slides 34 and 35). The supplemental descriptive efficacy analysis showed 90.7% vaccine effectiveness against symptomatic COVID-19 after the second dose. There were no cases of myocarditis/pericarditis after the data cutoff time.

FDA presenter Dr. Hong Yang, PhD presented the Benefit-Risk Analysis. Slide 22 summary:

“• For Scenarios 1 (Base), 2 (Recent COVID-19 Peak Incidence), 4 (Higher Vaccine Efficacy), 5 (Higher COVID-19 Death Rate), and 6 (Lower Excess Myocarditis Rate) the model predicts that benefits of the Pfizer-BioNTech COVID-19 Vaccine 2-dose primary series clearly outweigh the risks for ages 5-11 years.

• For Scenario 3 (The Lowest COVID-19 Incidence), the model predicts more excess hospitalizations and ICU stays due to vaccine-related myocarditis/pericarditis compared to prevented hospitalizations and ICU stays due to COVID-19 in males and in both sexes combined.

• Considering the different implications and length of stay for COVID-19 hospitalization versus hospitalization for vaccine-associated myocarditis/pericarditis, and benefits related to prevention of cases of COVID-19 with significant morbidity, the overall benefits of the vaccine may still outweigh the risks under this lowest incidence scenario.

• If the myocarditis/pericarditis risk in this age group is lower than the conservative assumption used in the model, the benefit-risk balance would be even more favorable.”

“Major Limitations of the Benefit/Risk Model:

• Model assumption about constant incidence rate generates great uncertainty on the estimate of benefits.

• Vaccine efficacy may change due to new emerging variants of virus

• Hospitalizations and ICU stays from COVID-19 and myocarditis are not equivalent and cannot directly compared

• The benefit of reducing COVID related multisystem inflammatory syndrome in children may not be fully captured by preventable hospitalizations, ICU stays and deaths due to COVID-19

• This BR risk assessment does not consider potential long-term adverse effects due to either COVID-19 or myocarditis

• This BR assessment does not include secondary benefits (reducing COVID-19 disease transmission) and risks”

Break.

There were complicated questions about the applicability of the Benefit/Risk model assumptions, partly because it can be influenced by a low incidence of disease-readily acknowledged by the presenter, Dr. Yang. After extensive discussion, including the about the number of doses (One or Two?), concern for the difficult decisions this presents to parents (not just related to side effects), concern about the FDA approval being interpreted as a mandate, discomfort with the binary choice-type question.

A representative from the CDC Advisory Committee (ACIP) expressed that it seems the benefits outweigh the risks. The ACIP representative summarized the safety monitoring and reporting systems available, including but not limited to Vaccine Adverse Effects Reporting System (VAERS). The FDA can make a broad authorization; the ACIP (which may meet on this issue as soon as next week) can make implementation recommendations that could be more restrictive but could not be broader. University of Iowa representative, coronavirus expert with over 40 years’ experience and temporary voting member Dr. Stanley Perlman, indicated, in light of the thorough discussion, that he would vote in favor of the question.

“Based on the totality of scientific evidence available, do the benefits of the Pfizer BioNTech COVID-19 Vaccine when administered as a 2-dose series (10 µg each dose, 3 weeks apart) outweigh its risks for use in children 5-11 years of age.” Please vote yes or no.

The Vote: The votes were 94% (17) Yes, and there was one abstention, out of 18 votes.

The meeting was formally adjourned at 4:35 PM, ET.

FDA Advisory Committee on Janssen Booster and Heterologous Dosing: Day 2

Dr. Arnold Monto, Acting Chair “Arnie” couldn’t get his camera to work right off the bat on this, Day Two of the FDA Advisory Committee meeting on COVID-19 vaccine boosters. The microphone mute virus was also an issue—again. One committee member had real problems with audio skipping, which the on-screen captioning could not fix. There were many on-screen notices of “indiscernible,” as well as comical errors, “public urine speakers.” That captioning reminded me of voice recognition software, which I tried to use when I dictated my clinical notes.

Early in the meeting, Arnie asked for a clarification of the voting question:

“10/15 Voting Question:

Question 1) Do available data support the safety and effectiveness of Janssen COVID-19 Vaccine for use under EUA as a booster dose in individuals 18 years and older at least 2 months after a single dose primary vaccination?

1a. If yes to # 1, do available data support that an interval of at least 6 months between a single primary dose and a booster dose may result in a more robust booster response?

2b. If no to # 1, do available data support the safety and effectiveness of Janssen COVID-19 Vaccine for use under EUA as a booster dose in individuals 18 years and older at least 6 months after a single dose primary vaccination?”

This led to what Sena and I thought was a hilarious “clarification” interaction between Arnie and Dr. Peter Marks. We couldn’t really follow it, mainly because we couldn’t stop laughing.  It reminded me of the “Who’s on First” routine by Abbott and Costello. However, Arnie said he understood it.

The Q&A session between the committee, the sponsor, and FDA seemed conflicted about the data on the efficacy of the Janssen vaccine. The FDA received a large amount of data from Janssen, but apparently got it too late to conduct its own analysis of it. There was the overall impression that the Janssen vaccine efficacy is lower than the mRNA vaccines. The participants on both the FDA and the sponsor side acknowledged that maybe part of the reason to hold today’s meeting was in view of the urgency to do something for those patients who got the Janssen vaccine. Most people acknowledged that the Janssen vaccine had good durability. Arnie kept the proceedings on a short leash as usual, and by the break for lunch at 11:25 AM CDT, it wasn’t very clear what the outlook was for the Janssen booster.

I’ll update after the break.

Several committee members advanced the idea that the Janssen vaccine is actually best considered a 2-dose vaccine rather than a 1 dose vaccine. They moved toward not calling the 2nd dose as a booster per se, and also seemed agreeable to simplifying the voting question above to only number 1, setting aside the a and b questions. Arnie called out “We need a simplification” and the group went along with it. Dr. Perlman suggested that it might be helpful to hear the presentation about heterologous boosting prior to addressing the voting question; however, Arnie and Dr. Marks thought heterologous boosting might be addressed as a separate EUA in the near future.

The committee voted only on the revised question:

Question 1) Do available data support the safety and effectiveness of Janssen COVID-19 Vaccine for use under EUA as a booster dose in individuals 18 years and older at least 2 months after a single dose primary vaccination?

The above was upvoted unanimously. The word “booster” might be changed to something like 2nd dose later.

After a 15-minute break, the heterologous (mix and match) vaccine boosting presentation will be given. I’ll update after that.

After the presentation on heterologous boosting, it seemed like mRNA boosting was stronger than Janssen boosting. A limitation was that this was an antibody data study only. The committee was impressed with the safety data. The discussion question to the committee was about what other studies they would want to see in order to evaluate an EUA to help guide decisions on, for example, how to boost the Janssen vaccine. Not all members thought an EUA was necessary for this issue. It sounded like some members wanted to see some flexibility in allowing for a fact sheet that would provide clear guidance on how to use heterologous boosting. In fact, some heterologous boosting is already happening out in the real world, which members acknowledged.

The meeting was adjourned at 2:30 PM CDT on the proverbial and a celebratory “You’re muted” reminder.

FDA Advisory Committee Meeting on EUA for Moderna COVID-19 Vaccine Booster Today

Today I’m watching the FDA meeting on extending the Emergency Use Authorization (EUA) for Moderna COVID-19 Vaccine Booster application. Right now, I’m in-between presentations and I’ll be updating later this afternoon. I’m skipping the Open Public Hearing.

I’m wondering if the question to vote on will get changed like it did last month for the Pfizer booster. So far, today’s question is:

“10/14 Voting Question:

Question 1) Do available data support the safety and effectiveness of Moderna COVID-19 Vaccine for use under EUA as a booster dose (50 mcg mRNA-1273) at least 6 months after completion of a primary series in the following populations:

• Individuals 65 years of age and older,

• Individuals 18 through 64 years of age at high risk of severe COVID-19, and

• Individuals 18 through 64 years of age whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.”

Dr. Arnold Monto is in fine form and has already starting limiting the number of questions participants can ask. But we’re ahead of schedule and he’s very pleased overall.

My wife, Sena, finally got her Pfizer booster this morning. It has been kind of complicated for her to schedule and she went through a telephone algorithm about a half dozen times. She showed up on the day scheduled a couple of days ago and the pharmacy manager cancelled it, saying it was too early for the 6-month mark (by 2 days) following her 2nd primary series dose. This morning he apologized for being the “Vaccine Nazi.”

My Moderna booster depends on what happens today, and after the CDC advisory committee makes its decision at their meeting next week Oct 20-21. If approved, I’d get half the dose I received during my primary series (50 mcg instead of 100 mcg)—provided I don’t run into the Vaccine Nazi.

Anyway, this morning’s meeting went fairly well; only 2 people forgot to unmute their microphones. The Israeli researchers gave a presentation on their updated booster program that impressed committee members, who called the data “compelling.” As I recall, last month, some people raised questions about their definition of COVID-19 disease severity, making it hard to judge how applicable their data results would be in the United States. This morning, they clarified that the disease severity criteria actually came from the NIH (slide 15).

Update around 2:15 PM today: The committee upvoted the question above unanimously.

Tomorrow the committee will take up the issues of J&J boosters and heterologous vaccinations.

Heeeeeere’s Arnie—at the FDA Advisory Committee Meeting

I got a big kick out of Acting Chair of the FDA’s Vaccine and Related Biological Products Advisory Committee. Dr. Arnold Monto at the FDA meeting last month for the Pfizer COVID-19 vaccine booster. Everybody else did too, I bet. They all called him Arnie. I’m looking forward to seeing Arnie in action again this week for the meeting on the other boosters, Moderna and J&J. They’ll also discuss mixing and matching vaccine boosters—if Arnie lets them.

Arnie is pretty good at keeping speakers on a timeline. Everybody has a short leash. “That’s all you can ask.” “Keep it short, or I’ll cut you off.” “Hurry up, people want to get out in their gardens.” (He actually said something like that toward the end of the last meeting). The end of the meeting was abrupt. Arnie evidently expected the Advisory Committee on Immunization Practices (ACIP) to tidy up the regulatory decision with which the FDA committee seemed to struggle regarding the Pfizer booster.

I’m not the only one who notices Arnie’s preference for terseness. I found the article “Hearing Without Listening” by David S. Hilzenrath, who posted it on the web, December 16, 2020 on POGO.

I think Hilzenrath was a little hard on Arnie. People do tend to talk too much at meetings and that can interfere with getting things done.

I wonder what Arnie thinks about the Moderna and J&J boosters and the heterologous vaccination dosing strategies (“mixing and matching”)? My impression of what I read in the news is that different experts might be purposely jazzing up the topic, sending readers in different directions decorated with teaser headlines and leading statements. One might say something like, sure, the booster does what it’s supposed to do, which is boost—but does it boost enough? Another might say the boosters are barely needed. Many of them tend to be identified as “former” directors of something or other.

I’m not sure I’ll pay much attention to the hour long open public hearing, 3-minute-long diatribes per speaker on the miraculous properties of lemon-freshened Ivermectin gummies, including breathless accounts of also witnessing armies of Bigfoot hacking hairballs at armies of Gray Aliens doing impressions of Elvis (“thank ya-thank ya very much”) all on the head of a pin. If YouTube is kicking out purveyors of COVID-19 vaccine misinformation, why can’t the FDA and CDC advisory committees do the same?

I wonder if Arnie will rush the upcoming meeting because has a butternut squash garden he wants to get back to as soon as possible?

OK, we’re done here. You need to pick your pumpkins.

FDA Advisory Committee Meetings on COVID-19 Vaccine EUA Amendments for Moderna, J&J Boosters and Heterologous Boosters, Pfizer Vaccine for Children

The FDA Advisory Committee will hold a meeting October 14-15 to discuss amendments to the Emergency Use Authorization (EUA) for Moderna and J&J COVID-19 boosters as well as heterologous boosting (mix and match). New data is available, including NIH preliminary results on the mix and match study.

The FDA also announced a meeting to discuss Pfizer COVID-19 vaccine for children age 5-11, which is scheduled for October 26, 2021.

Links to the livestream meetings details are in the press announcement (link above).

Meeting materials are posted here.

Watching Sausages, Laws, and FDA Advisory Committee Decisions Being Made

Sena and I watched the FDA Advisory Committee live streamed meeting yesterday on whether or not Pfizer’s COVID-19 vaccine booster should be given full licensure. You know, there’s a much-discussed question about who actually made the following quote:

“Laws are like sausages; better not to see them being made.”—often attributed to Otto Von Bismarck although it’s been attributed to others.

You can view the arguments about who said it at this link. The point is I think it should also apply to FDA meeting decisions. Our overall impression is that it was a messy process. We watched the entire daylong proceeding. The bottom line was that the committee revised the original question and reframed the approval from full licensure to Emergency Use Authorization (EUA):

The FDA approved the EUA for the booster based on the “totality” of the available evidence instead of just the originally specified Clinical Trial C4591001 (because of the small number of subjects including only a dozen in the older age group; the data from Israel was also fair game) and restricted the population to those age 65 and older (instead of the original 16 years and older). They further specified further that the booster should target those at increased risk for severe disease—which is to be understood to include health care professionals and others at risk for high occupational exposure.

One of the voting members disclosed candidly that his wife had already received a booster shot at a pharmacy well in advance of the meeting (technically off-label) and that he planned to do the same—after they unanimously approved the booster after the question was reframed. Sena and I both thought this was an extraordinary statement coming from an FDA advisory committee member.

The original question was voted down with only 2 of 18 members voting in favor. Dr. Stanley Perlman of The University of Iowa voted no on the original question and voted yes on the revised question. For many days now, the news has been reporting that a large number of people have been getting a booster shot despite the lack of FDA approval.

Dr. Arnold “Arnie” Conto M.D., the Acting Chair of the committee, after being asked to read the original question, slipped by indicating the age as “16 months” instead of “16 years.” He was instrumental in holding the committee members to staying on time for each phase of the meeting.

Dr. Conto: “Do the safety and effectiveness data from clinical trial C4591001 support approval of a Comirnaty booster dose administered at least 6 months after completion of the primary series for use in individuals 16 months of age and older?”

“I see someone has his hand raised. Do you have a question?”

Dr. X: Lips clearly moving but no sound.

Moderator: “Please unmute your mike” (Everyone was guilty of this oversight repeatedly throughout the day. One participant actually started speaking audibly and then leaned over and switched off his mike, possibly not to break the trend).

Dr. X: “Oh my, sorry about that. Arnie, we’re not sure on that part about “16 months and older.”

Dr. Monto: Oh yeah, I meant “at least 16 days and younger.”

Dr. X: Lips moving but no sound.

Moderator: “Unmute, please!”

Dr. X: “Oops, sorry! OK, Arnie. Does anyone know whether we’re supposed to vote on the time machine today, or will that be for the Advisory Committee on Immunization Practices?”

Christopher Lloyd: “I got that covered! Dang, I mislaid the keys to the DeLorean.”

We listened to those making short presentations at the open public hearing. They were each given about 3 minutes to make their statements. Some were in favor of the vaccine booster, others were not. Safety concerns were prominent, especially for giving vaccine boosters to children.

In fact, the committee seemed very ready to change the focus of the booster to place less specific emphasis on children. We imagine that’s part of the reason why the age range was adjusted away from specifying those 16 years and older (although they’ve probably been getting the primary series, even before the August approval of the Pfizer vaccine). One of the committee members asked, after the change of the age from “16 years” to “65 years” (but also specifying those at “high risk for severe disease”) whether that still meant a 16-year-old could get the booster. The answer was “yes.”

That made sense since children can have medical illnesses that increase their risk of serious complications from COVID-19 infection. But some committee members wondered about the 65 years of age cutoff, probably because they were not 65 years old. This and other speculations about how to specify the vulnerable population led to scrambling to get the meeting over because this was a question which the ACIP could clarify—and because it was getting very close to the end of the day.

We still don’t know when the ACIP is going to meet about the booster. They’ve added something for September 22 and 23, but I don’t find an agenda for it yet. Maybe they’ll have sausages for lunch.