Amgen is moving closer to submitting its closely watched cancer drug sotorasib for U.S. approval, announcing on Tuesday it had secured two regulatory designations from the Food and Drug Administration that could speed the agency's review.
The FDA will include sotorasib in its Real-Time Oncology Review program, which allows agency drug evaluators to begin assessing study results and analyses even before a formal request for approval has been submitted. Amgen said it has already started transferring data to the FDA under the initiative.
The biotech expects to file its full application for sotorasib by the end of the year, according to a Dec. 8 statement. The three drugs previously reviewed under the real-time program won FDA approval about three months ahead of schedule, suggesting sotorasib may be cleared by mid-2021, Piper Sandler analyst Christopher Raymond wrote in a note to investors.
Sotorasib is the crown jewel in Amgen's research pipeline and represents a step forward in cancer research after four decades of scientists trying unsuccessfully to target tumor-fueling mutations in a gene called KRAS. The gene is often altered in lung, colon and pancreatic cancers.
Sotorasib binds to KRAS proteins produced by one such mutation, called G12C. The drug's first target is in non-small cell lung cancer. Amgen is seeking approval for patients with locally advanced or metastatic tumors who have already received at least one systemic therapy and test positive for the mutation.
KRAS G12C mutations are found in the tumors of an estimated 25,000 newly diagnosed non-small cell lung cancer patients each year, Amgen said.
Results from an early-stage study showed sotorasib shrank tumors in about a third of patients, about twice as many as would be expected with chemotherapy. Among the study participants, median progression-free survival was about six months, an improvement over other treatment options but still only a modest benefit.
More recently, Amgen said a Phase 2 trial showed similar efficacy, but data have not yet been released.
The drugmaker is testing sotorasib in combination with other drugs and in a dozen tumor types, part of a broad clinical program that's delivered data in more than 600 patients to date.
Sotorasib has company, however, as a wave of new KRAS-blocking drugs advance through or into clinical testing. Mirati Therapeutics, Johnson & Johnson and Boehringer Ingelheim are among the other companies working on ways to target cancers driven to growth by KRAS mutations.
Analysts expect sotorasib and its rivals to earn significant revenue, should they be proven in testing and approved. Piper Sandler's Raymond, for instance, predicts sotorasib sales may reach close to $1.4 billion within five years.
Ontarians who refuse to get the COVID-19 vaccine when it's available could face restrictions, the province's health minister says.
While Christine Elliott said the vaccine will not be mandatory in Ontario, things like travel and access to communal spaces like movie theatres could be restricted.
"There may be some restrictions placed on people that don’t have vaccines for travel purposes, to be able to go theatres and other places," Elliott said at Queen's Park on Tuesday. "That will be up to the individual person to decide whether they want to receive the vaccine to be able to do these things or not."
Elliott said Ontario will issue government documentation so that people can prove they have received the vaccine. She says the documentation will be "essential" to have as the province emerges from the pandemic.
She believes there are two types of people who are hesitant to receive the vaccine, “strict anti-vaxxers” and those who don't want to receive it first because they are still concerned about its safety.
"That’s their choice," Elliott said. "This is not a mandatory campaign."
Last week, Ontario's Chief Medical Officer of Health Dr. David Williams told reporters that while the law is clear that they can't "force someone to take a vaccine," mandatory proof of immunization may be required in some settings.
Williams said proof of immunization against COVID-19 could allow "freedom to move around" and access to facilities like long-term care. He said he believes it will also become required for attendance in schools.
"Our first shipments of a very small number of doses could arrive as early as next week," Premier Doug Ford said.
The province announced that once approved by Health Canada, Ontario will roll out the vaccine in three phases, beginning with long-term care, retirement home residents, and the staff who provide care to those groups.
Health-care workers, including hospital workers, and other staff who work or study in hospitals will be vaccinated in the first few months of the program as well, the government said.
Adults in Indigenous communities, including remote communities where risk of transmission is high, and adult recipients of chronic home health care are also included in those first to get the vaccine.
The chair of the COVID-19 vaccine distribution task force, retired Gen. Rick Hillier, said on Thursday at Queen's Park that the first phase will take about two to three months.
The vaccine will then be rolled out to a wider group, with it becoming eventually available to anyone who wants it receive it.
Pfizer and BioNTech have a date on Thursday in front of an FDA advisory committee to review their vaccine data, and the briefing document is available for all to read (here’s the FDA’s own document as well). It’s very interesting stuff, and far more information than we’ve had so far.
First off, safety. There continue to be no serious concerns that I can see. There were two deaths in the vaccinated group, and 3 in the placebo group (both about 19,000 people). More people withdrew from the study in the placebo group. There were 18 adverse events characterized as “life-threatening” in the vaccine group after one month of follow-up, but there were 19 of those in the placebo group, and so on (for two months of follow-up, those numbers were 10 in the vaccine group and 11 in the placebo). There were four incidents of Bell’s palsy (temporary facial nerve problems) across the total participants, all four of those in the vaccine group. That’s worth keeping an eye on, but it’s about the number of people you’d expect to show it in a population that size (Bell’s palsy is not extremely rare), and thus can’t really be associated with the vaccine with that number of incidents. The events that were clearly associated with the vaccine were reactogenic ones (injection site pain, soreness, stiffness, fever, headaches, etc.) Older patients tended to have fewer of these, having overall less active immune systems. Word has come this morning that two severe immune reactions have been seen in the UK, both in National Health Service workers with long personal histories of severe immune reactions, but in general, such people are at higher risk with any vaccine. I have not gone through every line of the safety material, but so far I do not see anything in there that would be a problem for Emergency Use Authorization or later full approval.
We also have a great deal of fresh data on the immunogenicity of the vaccine, both antibody response and T-cell responses. I’m not going to try to summarize those for now because (1) everyone mostly cares about the efficacy and (2) once we have more data of this kind with other vaccines we can try to make some sort of head-to-head comparison. In the Phase I studies, this vaccine showed robust neutralizing antibody levels and T-cell responses, and those numbers look to have continued in the larger Phase 2/3 study, as expected.
Now to efficacy. As we know, “overwhelming efficacy” was declared at the first (and only!) interim analysis, with 94 total cases split 90/4 between the placebo group and the vaccinated group. The final analysis shows 170 cases, split 162/8 (confirmed coronavirus infection at least 7 days after the second dose). That’s a VE (vaccine efficacy) of 95%, with the 95% confidence interval on that number running from 90.3% to 97.6%. A new and interesting data set cover what happened after the first dose and before the second. There were 50 cases of coronavirus in the one-dose treatment group, versus 275 in the placebo group. But look at how those 50 cases came on:
What you can see is that the great majority of those 50 cases happened in the first ten to fourteen days or so after the first shot. At that point, the vaccinated group and the controls diverge sharply, and that’s because ten to fourteen days is the time it takes to raise an antibody response after a vaccination. You can see it kicking in, right there in the chart. This vaccine, in fact, already meets the FDA’s threshold of 50% efficacy with just one shot (but has much greater efficacy, of course, with the two-shot regimen). It’s worth noting that 10 cases of severe infection developed in the treatment group after just one shot, versus only 1 such case after two shots.
Table 8 in the FDA’s document has a good look at the various subgroups in the vaccinated population, and it’s hard to see any real differences in there. Age, gender, body mass index, ethnicity, risk factors – to my eyes, there’s not much to choose from, and that’s a good thing.
So it looks like the vaccine has a very strong protective effect, and that’s the first thing you’d want to know. But there are many other things we don’t know yet. What, for example, is its effect on transmission of the disease? We should be seeing more on that early next year, but based on these figures, it seems very likely that this vaccination would cut down the transmission rate sharply. But that has to be proven; there are plenty of things that have seemed very likely over the years in drug development that haven’t worked out. Even at this point in the pandemic, we don’t have solid numbers about the correlation between just what sort of viral load a person is carrying and their infectiousness to others. Think about how you’d try to design such a study and you can see why the data are lacking! We also don’t know the effectiveness of the vaccine in preventing asymptomatic infections, because this trial was based on symptoms, not on constant PCR testing of its participants, which is the only way you’d accumulate such data. The stronger knockdown of severe cases makes one think that asymptomatic cases might be similarly decreased, but you could also imagine that you would take what would be “normal” symptomatic cases and knock them back to being real-but-asymptomatic ones. A priori, you can’t be sure what the real situation is. That question is tied up with the transmission one, of course. We also don’t know what the duration of protection is, for the very simple reason that time just has to keep on tickin’, tickin’, into the future, (S. Miller et al.) for us to have any data on that. There’s no other way; we can’t estimate these things. That we will certainly have data on – eventually.
The data that Pfizer and BioNTech have presented look like far more than would be needed for an Emergency Use Authorization. I expect the FDA to grant that, and very soon. All the concerns about the effect of one or more EUAs that I wrote about here are still real. But some of them are less troublesome now that both this vaccine and Moderna’s have read out with such high efficacies – I was most worried about the first vaccine candidate showing decent-but-not-great effects, and that fortunately has not happened. But questions about (for example) the Pfizer placebo group switching over to vaccine, about the effects of these EUAs on other vaccine trials, and so on are still with us, and are yet to be resolved.
At any rate, any EUA is going to be accompanied by a large monitoring requirement. We’re going to be collecting a lot more data on this vaccine and others as they move into larger populations, data on both safety and efficacy. Vaccine work has its unique challenges because of its unique situation of dosing huge numbers of people who aren’t sick yet, and because of its targeting of the wildly complicated, wildly variable immune system. If there is some nasty side effect that is literally at the one-in-a-million level, which given immunology is absolutely possible, we certainly would not expect to see it in a 38,000-person trial (huge though that is by clinical trial standards). But we certainly would see it after dosing a few hundred million people.
Remember, though, what an EUA is for. That word “emergency” is there for a reason: this authorization is for something extremely serious for which there is no available alternative. That’s exactly the situation we find ourselves in, on both counts, and I think that the risk/benefit ratio is clearly, overwhelmingly in favor. Let’s do it.
We now have a complete writeup of the efficacy data from the Oxford/AZ vaccine effort in The Lancet, and I’m glad to see it. There have been a number of questions about this candidate and its effects in the clinic, so the chance to get a closer look is welcome.
This is of course the “ChAdOx” vaccine, with the first part of that acronym standing for “chimpanzee adenovirus”. And it’s the first viral-vector candidate that has reported out. J&J is coming soon with their adenovirus-26 vector, perhaps even sooner than expected due to the terrible number of coronavirus cases in the US, and Russia’s Gamelaya Institute has their one-shot-of-adenovirus-5 and one-shot-of-adenovirus-26 vaccine as well, for which data are unfortunately very sparse. This paper is from the UK, South Africa, and Brazil trials (others are ongoing), with a total of over 23,000 participants. The portioning of those into treatment and control groups, though, is where some of the arguing starts. These trials are notable for using an approved meningitis vaccine in the control group in the UK trial, rather than saline (as indeed the US trial of this vaccine is doing). The Brazil arm did that for the first shot, with saline for the second, and the South African trial used only saline controls. Famously (by now) a subset of patients in the UK trial got a half dose of vaccine first, followed by a full dose as booster, which seems to have been an out-and-out mistake in handling and formulating the vaccine. Update: here’s the New York Times on the various mistakes that have been associated with this one. Among those is a further difficulty with the half-dose vaccine group – some of them got their booster shots much later than others, for unexplained reasons.
In the larger cohort who got the two regular doses, vaccine efficacy was 62% (with a 95% confidence interval of 41% to 75%). There were 27 cases in the 4440 treatment patients, compared to 71 cases out of 4455 patients in the controls. Meanwhile, in the half-dose-first group, efficacy comes out at 90% (with a 95% confidence interval of 67% to 97%). Both of those 95% CIs are a bit of a spread. In this group, 3 out of 1367 patients in the treatment group came down with coronavirus, compared to 30 out of 1374 in the controls. That control-group infection rate is definitely higher than what was seen in the two-full-dose group, which makes you wonder if it’s running randomly high (which would make the half-dose group look better than it really is) or if the larger full-dose group was running randomly low (which would make it look worse than it really is, but remember, with its larger sample size there’s correspondingly somewhat less room to believe that it was that far out of whack). We need to add in to these calculations the news that the half-dose group included no patients older than 55, and to wonder what effect that had on the numbers, too. The paper reports a combined overall efficacy of 70.45 (95% CI between 54.8% and 80.6%), but how much you trust that one comes down to how different you think these two groups are.
Basically, the more you believe the 90% number is a statistical fluke, the more you then believe that the real efficacy of the vaccine is probably in the 60-per-cent range. On the other hand, if you buy into the idea that there’s something really different and useful about giving everyone a half dose at first, you can be somewhat more optimistic. That belief is optimistic in itself, but it’s not completely nuts, either. Remember, one of the things about a viral vector is that you raise antibodies not only to the protein that whose genetic message you’re delivering, but to the viral vector itself. It’s not impossible that a lower dose the first time made subsequent antibody neutralization of the second dose less of a problem. But you’d need to prove that. And to prove, with intention, that a half-first-dose really does work better to start with.
A bright spot in the data is that (counting from 21 days after the first shot) there were overall ten hospitalizations for coronavirus (two severe, one leading to death), but none at all in any of the treatment groups. This would be a good point to note that the coronavirus cases totaled in all these trials were based on symptoms, which were then confirmed by RT-PCR swab assays. The UK trial also had regular swab assays taken to try to get data on asymptomatic infections, which is something that wasn’t done in either the Pfizer/BionTech or Moderna trials. The numbers aren’t huge, and they aren’t tight, but they’re all we have. There were 24 asymptomatic patients in the low-dose-first group, for a vaccine efficacy of 58.9% (95% confidence interval from 1 to 82.9%, and that’s what I mean by “not tight”), and 45 patients in the two-standard-dose group (efficacy of 3.8%, unfortunately). So at least for this vaccine, the efficacy at preventing asymptomatic cases is notably lower than that seem for symptomatic ones, and that may well be true for all of them. The differences in those asymptomatic numbers, though, also argue that the low-dose vaccination regimen was indeed different from the two-standard-dose one, don’t they?
Now to safety. The top line numbers look reasonable, with the usual reactogenic effects in the treatment groups, and with very similar numbers of adverse events in the treatment and control groups. The part that makes you wonder a bit, though, is the case of transverse myelitis (which made quite a bit of news at the time, at least once the details rather grudgingly emerged). This was two weeks after the second vaccination, and considered by the monitoring committee as likely to be related to the vaccine. It turns out that there were two more, but that news isn’t as bad as it sounds. One of these was in a participant who (as it turned out) had undiagnosed multiple sclerosis, so that’s less likely to be related to the vaccination. The other was in one of the meningitis control arms. It sounds like there was some arguing about whether that was vaccine-related or not (it was 68 days after the shot), but it’s certainly not related to the coronavirus vaccine, anyway. There still is that one case, and transverse myelitis is one of those neurological syndromes that can indeed be associated with autoimmune function (and thus possibly with vaccination). So this will bear close watching as this vaccine gets rolled out.
Which brings up the question of when that might be. As I understand it AstraZeneca is even now wrestling with the problem of whether to run another trial using that low/high dosing protocol. If the different results seen here are real, that could be a significant improvement, both in overall efficacy and in using up less vaccine, but there’s also a real chance of chasing after a mirage. If you go with the numbers as they are, though, it would seem that this vaccine is likely to be provably inferior to the Pfizer/BioNTech and Moderna mRNA ones. That doesn’t mean that it’s not good enough to be useful in the pandemic – just that there are others that could be even more useful, if you could deploy them instead. As it stands, there’s a real risk of having some patients (or indeed whole countries) feel as if they’re being dealt a second-class vaccine if this one is their only option.
Naturally, the same questions apply here as were mentioned in the Pfizer article that I posted earlier today – duration of action, effect on viral transmission, and so on. We’re going to have to wait and collect more data to be able to say anything about these, for any of the vaccines. But the data today make me quite curious about the coming J&J data. That’s another adenovirus vector, as mentioned, and there’s at least a possibility that we will then have a good head-to-head comparison between mRNA vaccines and adenovirus vector vaccines for the same pathogen. That’s a pretty strange situation – when did we ever have multiple simultaneous vaccines for the same disease? And there’s the Novavax recombinant protein one coming after that. No, this is a unique situation. Let’s hope it stays unique!
Update: it looks like India’s regulatory authorities have already declined to issue an accelerated approval for the Oxford/AZ candidate, which may be a sign of trouble to come. . .
Data related to a Covid-19 vaccine developed by Pfizer Inc. and Germany's BioNTech SE were accessed in a hack of Europe's top medicines regulator.
BioNTech and Pfizer said they had been told of the cyber breach by the European Medicines Agency, the Amsterdam-based agency responsible for approving new medicines for the European Union. In identical statements Wednesday, the companies said that some documents relating to its regulatory approval submission "had been unlawfully accessed."
It's unclear what documents were accessed. Pfizer and BioNTech have submitted reams of data to regulators in the U.S., Europe and elsewhere in an effort to win regulatory approval for their vaccine. Some of that data is typically widely disseminated, including, eventually, for academic peer review. But the submissions also include records related to manufacturing and human clinical trials, which cyber experts have said could provide an edge to others trying to refine their own processes or disrupt a vaccine rollout.
The breach hits at the very core of the Western world's race to roll out a Covid-19 vaccine, and it demonstrates the extent to which hackers have sought to infiltrate companies and institutions crucial to the fight against the pandemic. It follows earlier attempts to break into systems at universities and pharmaceutical companies involved in drug development and other pandemic responses, all seen as key to helping countries restart economies gutted by the virus.
BioNTech and Pfizer said no systems belonging to the two companies had been breached in the attack, and they said they didn't have evidence that any clinical-trial participants had been identified. They said they received assurance from the European agency that the hack wouldn't affect the timeline for review of the vaccine, which is scheduled for review by the agency Dec. 29.
The vaccine was deployed this week in the U.K.--the first Western-developed Covid-19 shot administered to humans outside of trials--and won authorization Wednesday in Canada. The U.S. Food and Drug Administration is expected to authorize use of the vaccine as soon as later this week.
The EMA, which approves new drugs in a similar capacity to the Food and Drug Administration, had earlier posted a statement that it had been targeted in a cyberattack that's now under investigation by law-enforcement and other officials.
The European agency didn't provide details or say whether the attack had affected its operations or disclose whether any data had been lost. "EMA cannot provide additional details whilst the investigation is ongoing," it said in a short statement on its website. The EMA later said via a spokeswoman that it is "fully functional and all work continues."
The attack follows months of warnings and ramped-up defenses across Europe, the U.S. and beyond against hackers targeting pharmaceutical companies, universities and other entities involved in Covid-19 treatments, vaccines and virus-tracking technology.
Last month, Microsoft Corp. said cyberattacks originating in Russia and North Korea have targeted online accounts at companies working on Covid-19 drugs and vaccines. The company said targets included pharmaceutical companies and vaccine researchers operating in the U.S., Canada, France, India and South Korea.
Some cybersecurity experts said the data handled by the agency wouldn't have necessarily included the most sensitive details of how the vaccine is designed or manufactured. It is also relatively late in the vaccine process for a rival state or company to attempt to duplicate Pfizer and BioNTech's efforts.
"If you are interested in stealing IP, there are better ways to steal it," said David Robinson, the co-founder of cybersecurity firm Internet 2.0 and a consultant to a leading Covid-19 vaccine maker.
With the latest coronavirus wave producing record numbers of cases, hospitalizations and deaths across the United States, the USA TODAY Editorial Board spoke Monday with Dr. Scott Gottlieb, former commissioner of the Food and Drug Administration. Gottlieb, 48, serves on the board of Pfizer, which is asking the FDA to authorize the company’s vaccine for emergency use. Questions and answers have been edited for length, clarity and flow:
Q: Even as the Pfizer vaccine could be approved as early as Thursday, we're in the midst of the worst surge yet of the coronavirus. How bad is this going to get before it gets better?
A: I think it's going to get a lot worse before things start to improve. The hardest four to six weeks are ahead of us. I think we're going to see daily new infections continue to increase for the next four weeks. And then we won't hit peak hospitalizations until probably six weeks, maybe mid-January. We could see upwards of 150,000 to 175,000 people hospitalized when we hit the peak and maybe upwards of 40,000 to 50,000 people in the ICU. That's going to really press the health care system.
Q. What about deaths?
A. By the end of this year, we'll probably be at around 300,000 Americans who have lost their lives as a result of COVID, and toward the end of January it could be around 400,000. So the most difficult period of this pandemic is ahead of us (before) things will get better. This is really, I think, the last surge of infection. That doesn’t mean coronavirus is going to go away altogether.
A: I'm optimistic about 2021. There's some disagreement about how quickly things will get better. I think things will get better very quickly, in part because probably 100 million Americans will have been infected by the end of January and in part because we're going to start rolling out a vaccine that seems to be very effective, based on the initial clinical studies.
Q. When should we start to see improvement?
A. As we get into probably February and certainly into March, I think you're likely to see the virus largely collapse. And I think that we're going to enter a period, over the spring and the summer, when it's going to be relatively quiescent. We'll see cases get reported, but we're not going to see major spread. There'll be sporadic outbreaks. I fully expect kids will be back in summer camp and people will be having barbecues again outdoors.
Q: What about the rest of 2021?
A: As we head into the fall, we face renewed risk that there's going to be outbreaks. But at that point, hopefully there's vaccines that are widely available. We'll be vaccinating the population for this before the fall COVID season. And we'll go into the winter with a population that's largely protected and has immunity. And so, while it will spread, it will spread far less.
Q: When do you see a return to large events like concerts, weddings and sports with fans in the stands?
A: If you have a vaccine that's effective and widely deployed, and a virus that has circulated through the population, I think we'll return to gatherings and indoor gatherings next year. There's going to be some precautions taken, and I don't think that we're going to do things next year like we did in 2018. Customs are going to change a little bit. I think you're going to see masks more generally worn in airports and public transportation, and it's not going to be something that's objectified or looked upon strangely.
Q. Could continuing certain precautions have other benefits?
A. Remember, these mitigation steps — the social distancing, the mask wearing, all of the things we're doing — were really designed as a way to stop a flu pandemic. They weren't designed with coronavirus in mind. They seem to be much more effective at breaking chains of transmission of flu than even breaking chains of transmission of COVID. So whatever we do to try to mitigate the risk of COVID, we're probably going to see in terms of sharply decreased rates of flu. That’s going to have a very direct payoff in terms of not just improved health, but also productivity gains.
Q. Once vaccines are approved, what does the rollout look like?
A. It's very clear that the first people to get it are going to be health care workers and elderly people who live in congregate settings, such as nursing homes and long-term care facilities. Then there's some debate about what the next tranche of eligible people is going to be. This is going to feel to most Americans like a difficult process. For a time, demand is clearly going to outstrip supply.
Q. How long does that period last?
A. I think we're going to see an inflection point here at some point in the spring where, all of a sudden, a commodity that was very scarce and hard to get is going to become much more plentiful. I don't know where that inflection point is, when supply is suddenly going to really come online. But my guess is it's going to be sometime around March that we're going to see a lot more vaccine in the market. What seemed like a scarce commodity that was being very tightly rationed will suddenly become more generally available to most Americans.
Q: There's worldwide demand for the vaccine. How does Pfizer decide how much to give the United States, the United Kingdom and the other countries that are clamoring for it?
A: Well, it’s largely 50-50. Pfizer's production is split across two facilities, one in Europe and one in the United States. When the company said we'll have 50 million doses available in December — 25 million for the U.S. and 25 million for the non-U.S. markets — most of those doses have already been manufactured and are ready to go. So there shouldn't be any issue with getting that supply available for December.
Q: Why was the U.K. able to roll out the vaccine faster than the U.S.?
A: They deployed the vaccine quickly once the authorization was given. We're going to deploy the vaccine quickly once an authorization is given here in the U.S. So I don't think there's any difference there. The difference was that they authorized it before we did. But we made deliberate decisions about our regulatory process for understandable reasons, for prudent reasons, that ultimately delayed the authorization of this vaccine by a matter of (two, maybe three) weeks.
Q. If the FDA grants the emergency use authorization, how long will it be until vaccines are administered?
A. When the United Kingdom authorized the vaccine last week, there were trucks, Pfizer trucks, rolling into the United Kingdom through the Chunnel, delivering supplies into the U.K. And so those vaccines are prepositioned right now. The U.K. said they're going to start to vaccinate as early as (Tuesday) and may vaccinate upwards of 800,000 people this week. And the same thing is going to happen in the U.S. as soon as the company gets the authorization from the government that this vaccine is authorized to be made available. It will be shipped immediately to locations that have already been predetermined as vaccine distribution points. And so, it will be immediately available.
Q: For the Pfizer and Moderna vaccines, each person is supposed to get two doses, three or four weeks apart. Between the two companies, 40 million doses are expected to be available in the U.S. this month. Is it better to give 20 million people two doses, one in December and one in January, or get all 40 million out there and then catch up to the second dose as supply increases?
A: I feel very strongly that we should get as many shots in arms as possible, right away. The reality is that one dose is partially protective. I just fundamentally disagree with (saving half the supply for January) because, the reality is, supply reacts very quickly in 2021. If something happened and we didn't have supply available in 2021 to give everyone who got the first dose in December their second dose, we're going to, quite frankly, have bigger issues. It's going to mean that there was something that went wrong with manufacturing, and we're not going to have enough supply for January and February and perhaps March. So I don't think we should be holding on to supply now, anticipating that something goes wrong that's going to cause a lot of other challenges.
Q. Isn’t that a gamble?
A. We should be taking some risk. This is an environment where there is a widespread pandemic causing immediate death and disease. This is the type of environment where you take some risk and try to get as many doses out as possible in December, recognizing that this is going to be over in a couple of months. What we do right now is going to determine how many lives we can save. Holding on to a shot now — so we can give it by the end of January when this epidemic across the U.S. has largely run its course and is starting to decline — that fundamentally doesn't make a lot of sense to me.
Q: Who ultimately will make that decision?
A: Well, it's going to be Health and Human Services and Moncef (Slaoui), who's head of Operation Warp Speed, and some of the logistics people who are managing that. They seem to be heading in the direction of making the decision that they're going to hold on to some supply and not deploy all the vaccines in December. I think it would be a shame to have stockpiled vaccine in December so you can have it on the shelf at the end of January, right as this epidemic has run its course and we're starting to see declines in the number of daily new cases.
Q. What makes you think that will happen?
A. We've seen these epidemic curves before. They are sharp up and they're a sharp trip down. At some point in January, this virus is going to start to decline very rapidly. And if we've stockpiled vaccines that we could have given to people who could have benefited from that in December, so that we could have it sitting on the shelf right at the time that the virus is declining, I don't see us maximizing the public health utility of this product that way.
Q: When does this decision have to be made?
A: This is a decision that is going to get made and play out over the month of December. This is a question of how many people do we get vaccinated in December. I think this is really borne of probably some hesitation that they don't have full visibility into the manufacturing supply chain. Look, I don't have any more visibility than they do. They probably have more proximity to it than I do, notwithstanding the fact that I'm on the board of Pfizer. But No. 1, I have confidence that things will go well. And No. 2, I think in a circumstance like this, you need to have that confidence. You need to take a little bit of risk and hope things go well, because if things don't go well, like I said, we're going to have bigger problems. It's not just going to be that we can't get everyone a second dose on time. It's going to be we can't get anyone new a first dose. And so, we need to kind of hope for the best and take a little bit of risk that things will work out well.
Q. How can you influence the decision?
A. I don't have any way to influence this other than speaking out publicly. I think it is a fundamental mistake to take a vaccine and put it in a warehouse somewhere on a shelf when people could potentially be benefiting from it right now. We have a very acute period where we're going to see a lot of death and disease. And they've said as much. They said the next six weeks are going to be the hardest period in the history of America. So during the hardest period in the history of America, you're going to take some vaccine that could potentially be better for some people and lock it in a drawer? Fundamentally, that doesn't make sense to me.
Q. How many people ultimately need to be vaccinated?
A. If you have a vaccine that continues to demonstrate the profile that these vaccines have shown, that's widely accessible and largely used, you don't need to vaccinate 80% of the public. I mean, if you get to 50%, that's going to be a pretty effective target. Anything above that, I think is just sort of additional benefit.
Q: When would we know whether that’s going to be enough?
A: Partly it's going to depend on what we learn about the vaccine. Does the vaccine just prevent signs and symptoms of COVID, or is it actually preventing infection? Is it reducing someone's likelihood of spreading the infection? Depending on what the answers are, that's going to influence how many people you need to vaccinate in order to achieve a level of immunity that really stops the circulation of the virus.
Q. What should Pfizer and the FDA be doing right now to build public trust in vaccines?
A. In terms of how to inspire public confidence, I think that we need to be doing everything we can to collect data about the safety profile of these vaccines and also answer these questions about the true benefit. Are they preventing infection? Are they preventing viral shedding?
Q. What else?
A. It is going to be important to get some people to vaccinate themselves publicly, to assure the public of their confidence in the vaccine. I know former presidents have talked about getting vaccinated in public. Find a few celebrities and a few influencers, people who other individuals trust. Get them vaccinated early, get them vaccinated on TV. I used to always get my flu vaccine on TV every year. I felt it was important that the FDA commissioner get vaccinated publicly for flu. So people saw me getting vaccinated and saw me expressing my confidence in the vaccine. We're going to need to do things like that with this vaccine.
Q. Won’t people complain if celebrities seem to be jumping the line?
A. I think the public interest is very well served if we could find some people who are willing to step out and make a public statement and vaccinate themselves regardless of where they fall in the queue. And I would put the former presidents at the top of the list, and probably some other social media influencers and celebrities.
Q: Is it going to be a big problem to deploy the vaccines, particularly when you think about the storage and the extremely low temperatures that are needed?
A: I don't think that the actual mechanics of the distribution is going to be the challenge. I think the bigger challenge is going to be, as long as we're in this rationing phase, trying to apportion it equitably. If we make decisions about which group should be eligible, making sure we can actually find those individuals and verify their "eligibility." The logistics of storing (the vaccine), creating the injection sites, I think that's largely been worked out. Nothing goes completely smoothly, but there's been a lot of thought put into this.
Q: Are you worried about the virus mutating each year like the flu? Will we need a new version of the vaccine next winter?
A: I'm not that worried about it. This virus is going to drift, and there are going to be mutations. But the idea that you're going to see a very rapid mutation, one that becomes the predominant form within one season and would just obviate the vaccine, is unlikely. That doesn't mean that you wouldn't be reformulating the vaccine every two or three years (based on) how the virus itself has evolved over time. You probably will, but that should be a relatively straightforward process. So I'm not worried about waking up one day and finding, all of a sudden, the vaccines don't work anymore.
Q: Did this outbreak in the U.S. unfold in an even worse way than you anticipated?
A: I think it's extending longer. The peak is going to be larger than we anticipated, in large part because we haven't taken any real policy response. When you think about these kinds of epidemics, you always expect there to be a compensatory change in behavior and policy. As things get worse, people start to stay home or they wear masks more. Businesses take more precautions. Policymakers step in. I think that the sort of response to this has been much slower than I would have anticipated.
Q. What else was surprising?
A. The other part of this that I think was unanticipated was the big wave of infection in the summer. What many of us didn't necessarily see was that in the South, people would be going indoors to get the benefit of air conditioning in the summertime and going into congregate settings, into high-risk settings, and that you would see that big wave of infection that swept Texas and Arizona and Florida. So we never really had a period where there wasn't a lot of infection somewhere in the United States. That set us up for a much more dangerous fall where the country was already heavily seeded. Then you had (the big motorcycle rally in Sturgis, South Dakota), which was a superspreading event. And so the Midwest got very heavily seeded. Now you have sort of infection everywhere. It's really a confluent epidemic across the whole United States.
Q: Do we have a two-tier medical system where some patients have better access to treatments, such as monoclonal antibodies, than others?
A: The antibodies are definitely being rationed right now, and they're not widely accessible. Where you present for care and how aggressive your physician is in advocating for you is going to probably impact on the margins of your ability to get access to those drugs, unfortunately. There is, I think, an element of truthfulness in the fact that, where you go, who your doctor is, how strongly they advocate for you is going to have some impact on your ability to get access to these scarce antibodies, at least over the next couple of months while they're still in short supply. There'll be ample supply at some point in 2021.
Q. Did it have to be this way?
A. These didn't need to be in short supply. Many of us, including myself, were writing and advocating back in April and May that we should start trying to requisition biologics manufacturing capacity, recognizing that the antibodies were going to be available at some point in the fall. They were the most likely therapeutics to be available that would have an impact on the disease. This was a foreseeable problem. There's things we could still do now to try to increase manufacturing capacity, have more of these drugs heading into next year. We just didn't do it.
Q. What happened?
A. The companies themselves went through a lot of steps, really extraordinary steps, to increase their manufacturing capacity. Regeneron literally moved products that they manufactured in the U.S. out of the U.S. to free up domestic manufacturing capacity just to make these antibody drugs. But, ultimately, we needed to have the government step in and try to pay some companies probably to turn over their manufacturing capacity for other drugs to the U.S. government to manufacture these antibodies and also potentially build new facilities.
Q. How long would that have taken?
A. Building a biologic facility would typically take two years. If you really crash it, maybe you can get it done in a year. (If we) started this right at the outset in March or April, there's a chance we could have had some facilities coming online right now, if we really would have put a concerted effort into doing this and it would have made a difference. So these didn't need to be in short supply. I think we need to rethink in the future how we approach these kinds of problems, because there's things we could have done here.
Q: There still seems to be a lot of confusion about airborne transmission of the virus versus surface transmission from things like packages or serving utensils or doorknobs.
A: As far as touching a contaminated surface and getting a virus, that seems to be far less of a risk than we initially thought. That doesn't mean it's not a risk. You can still get the virus through touching contaminated surfaces and then rubbing your eyes. So good hand hygiene is still something that's simple and prudent. But it seems that most of the spread, and maybe the vast majority, is through droplet transmission and maybe some aerosolization of the virus.
Q: President-elect Joe Biden plans to nominate former congressman Xavier Becerra for HHS secretary. Under the circumstances, should he have picked someone with more of a public health and science background?
A: I don't really have an opinion, to be perfectly frank. I don't know the congressman other than by reputation. Above all else, HHS is really a management challenge. It's a political job. It's a management job. And so I think having someone with a pedigree where they have political experience, where they have management experience, probably are the two most important variables. Public health experience is certainly important, being able to speak the language, but a lot of people who don't have a clinical background or don't come out of a deep public health background can speak the language.
Q: Would you be interested in serving in the Biden administration?
A: I’ve had a couple of discussions with the transition team just to give them some advice. They've reached out to me. I've not had any discussions with the administration about any role. I've tried to make myself accessible to the governors and be helpful to the states. I don't foresee a future in politics right now or serving in any kind of government capacity for myself. I really don't. But I'm available. I pick up the phone, I call people back, and I try to be helpful to whoever I can.
Libraries in Japan are hoping a machine that sterilizes books using ultraviolet light is giving visitors reassurance to take-out publications during the coronavirus pandemic.
Libraries across the country are installing the machine, which takes 30 seconds to sterilize a book using UV light and flutter it pages to clear out dust.
The Narimasu Library in Itabashi, north of Tokyo, has had a machine installed since 2018 but the facility’s manager said that it is now being used three times as much.
Patrons can use the machine, which sits next to the front desk, once they have out a book and then again upon its return. However, this is not compulsory.
For many of those in the library on Wednesday, the machine was as much a novelty as it was a COVID-19 deterrent.
Eriko Isozaki, who comes to the library weekly to borrow children’s books, said the machine entertained her son, who appeared fascinated with the blue ultraviolet light.
“I’m not sure how effective this is, but I think it’s better than nothing,” said Isozaki. “And it’s fun. My child seems to enjoy watching (the machine).”
Many of the library’s patrons are elderly and so keeping them safe is extra important.
Many of them used the machine when returning books, including 77-year-old Yasuhito Kobayashi.
“I feel relieved because it sterilizes the books... but I’m not sure if it’s actually effective,” he said.
Although Japan has avoided the vast number of COVID-19 cases and deaths seen in other countries across the world, it is now experiencing a third wave.
As of Wednesday, Japan had reported 167,330 coronavirus cases, with 2,458 deaths.
