“Operation Warp Speed” Moves to Warp 2: AstraZeneca Begins Phase 3, Experts Skeptical as Trump Administration Prepares for November 1 Vaccine Delivery, and Speed-Up May Involve an EUA

“Operation Warp Speed” Moves to Warp 2 AstraZeneca Begins Phase 3, Experts Skeptical as Trump Administration Prepares for November 1 Vaccine Delivery, and Speed-Up May Involve an EUA

Monday, AstraZeneca said it has begun Phase 3 trials of AZD1222, its COVID-19 vaccine candidate. This makes them the third firm to be in Phase 3 for the virus. As chronicled by CNN August 31 and updated September 1, the vaccine is developed with Oxford University and is backed by the US government. Up to 30,000 adults are being recruited with a focus on demographic and medical-condition diversity. The trials of AZD1222 are happening in Britain, Brazil, and South Africa; they are planned for Japan and Russia. AZDD1222 is a weakened cold virus plus a protein from SARS-CoV-2.  

Emergency-Use Authorization Possible

August 23, TrialSite reported an “unprecedented compression” of vaccine testing timelines for COVID-19. We asked whether the White House was getting ready to fast-track AstraZeneca’s AZD1222. One tool reportedly considered was a EUA in October. Now, according to an August 30 article from CNBC, “FDA willing to fast track coronavirus vaccine before phase three trials end.” FDA Commissioner Stephen Hahn opined to the Financial Times that, “he’s willing to consider granting emergency authorization for a COVID-19 vaccine before clinical trials have been completed.” This was about a week after Trump had accused the FDA of deliberately moving slowly for political purposes. FDA’s chief is ready to bypass full federal approval processes to make a vaccine available as soon as possible. Hahn insisted that none of this is due to partisan pressure. He said that an EUA might be, “appropriate before phase three clinical trials are complete” if risks don’t outweigh benefits. “It is up to the to apply for authorization or approval, and we make an adjudication of their application,” Hahn offered. 

DHHS and AstraZeneca Deny Discussions

“If they do that before the end of phase three, we may find that appropriate. We may find that inappropriate; we will make a determination.” Hahn also said an EUA is not equivalent to full approval. The Financial Times revealed last week that Trump was thinking about a EUA before the November 3 election for a vaccine candidate developed in the U.K. by Oxford University/AstraZeneca. A DHHS spokesperson said these reports were “absolutely false,” while AstraZeneca says. “it has not discussed such a move with the US government.” Russia and China have each green-lighted vaccines prior to completion of Phase 3 trials. US officials have warned that this is unsafe.

Ethics May Require Terminating Successful Studies

As we consider that a study might be so “positive” that we don’t have to finish it, on September 2, CBS News reported that vaccine trials could actually be stopped early. According to Dr. Fauci, if results to-date show that a candidate is safe and effective, trials may be halted mid-study. An NIAID Date and Safety Monitoring Board, “has the power to end the trials early.” Fauci says that there would be a “moral obligation” to make a vaccine available to all study participants involved in a study in the case of “overwhelmingly positive” early data. And since there would be no more placebo group, this would necessitate an early end. CBS notes that President Trump has accused FDA of “slow-walking” vaccine tests to hurt his reelection chances. Also, in a recent Financial Times interview, FDA Commissioner Dr. Stephen Hahn indicated, “that he would be open to approving a vaccine before Phase 3 trials are completed.”

White House Aims for November 1 Vaccine Delivery, But Logistics Complicated

 On September 2, McClatchy reported on a CDC letter urging US governors to, “do everything in their power to eliminate hurdles for vaccine distribution sites to be fully operational by Nov. 1.” The August 27 letter asks governors to fast-track licenses and permits for distribution sites. In the meantime, the Trump administration has directed delivery firms to, “prepare freezer farms in the heartland” and prepare to load trucks with vaccine by November 1. Supply-chain experts are doubtful that the administration has adequately communicated responsibilities to state and local governments. Dr. Julie Swann, a CDC advisor during the H1N1 pandemic, says, “At this point, we should know much more about what the intended distribution system looks like, and what the plan is.” Most likely, the first vaccines will require sub-zero temperatures and two doses spread weeks apart. And there is concern that the November 1 date, two days before the election is politically motivated.

The president of UPS Healthcare, Wes Wheeler, said that the administration directed them to be ready by the November 1. “It will be preceded by a practice run – we’re talking about having early discussions in September and October about how this will actually work,” he indicated. “I think we’ll all be given instructions on how it will work – we haven’t seen that yet,” Wheeler reported. “They’re talking about ten million doses in November.” Dr. Larry Corey, co-lead for the COVID-19 Prevention Network under NIH, thinks that trial results will be adequate for the target date. But CDC’s vaccine working group has been meeting weekly in August, “to review potential scenarios for the initial distribution of the vaccine.” And Dr. Eric Tone, scholar at the Johns Hopkins Center for Health Security, opined, “I haven’t seen anything so far that’s given me a lot of confidence.” 

Immunization Registries Needed

States will have to create immunization registries on adults, so as to track who has gotten the first dose and who needs a second. Information will have to be constantly shared with distributors so that second doses arrive on time and at the right place. “If we are doing this as a mass vaccination campaign, in the parking lots of hospitals, then you’re seeing the person who is giving you the vaccine for the first time in your life,” according to Prashant Yadav, supply chain expert at the Center for Global Development and previous supply-chain leader at the Bill & Melinda Gates Foundation. “Then for the second dose, you would have a reminder from the county public health department or some other agency to go back, and would you go back to the same location? Or a different location?”

There are now two federally-backed candidates in Phase 3, vaccines from Moderna and Pfizer. AstraZeneca’s product must be kept in minus-20 degrees storage, and it started Phase 3 trials in the US on Monday, “but has recruited only three dozen people so far.” Moncef Slaoui, of Operation Warp Speed’s vaccine development program, “told a panel of independent experts on Aug. 7 that the only vaccine candidates which could possibly emerge for distribution by the end of this year were the vaccine candidates that had Phase III clinical trials already underway.” AstraZeneca’s candidate was not yet in Phase 3 when he said this. 

Rural Concerns

Rural areas are a special concern. The Kansas health department is warning that mass vaccination needing ultra-cold storage will be “impractical” for large parts of the state. “It will be a real challenge if we have to have things under dry ice. That’s not within a lot of clinics and health centers and rural facilities,” according to Dr. Lee Norman, of the Kansas Department of Health and Environment. “In laboratories and hospitals and things like that, we have that,” Norman opined. “But when it comes to pushing those out in the community, that will be tough.” Also, success of the public messaging campaigns will determine whether people will actually take the vaccine. Per a survey from Yahoo/YouGov, in May 55% of American’s planned to get the vaccine; in July, the rate was down to 42%.

Experts Skeptical of November Roll-Out

On September 3, CNN offered us a view of the potential dangers of rushing a vaccine. While CDC is telling states to prepare to receive vaccines as soon as late October, many doctors and health experts are voicing concern. These experts opine that early 2021 is more realistic for a safe and effective vaccine. But they also add that FDA could issue an EUA prior to the end of Phase 3 trials, “if the data is very promising.” Dr. Peter Hotez, who is dean at the National School of Tropical Medicine at Baylor College of Medicine, says, “How can you justify a substandard or lesser review for something that would be injected in tens of millions, maybe hundreds of millions of Americans?” 

While three candidates are in Phase 3, officials insist no vaccine will be released, “until it is deemed effective and safe.” NIAID’s Dr. Fauci indicates that is not likely to happen by late October. “If you look at the projection, of the enrollment (of trial participants) and the kinds of things you’ll need to get a decision about whether the vaccine is safe and effective, most of us project that that’s going to be by November, December, by the end of the year,” Fauci offered CNN Thursday. The New York Times weighed in on September 3, echoing skeptics. They note that Warp Speed’s chief advisor Moncer Slaoui says it is “extremely unlikely” to have a vaccine prior to the election. About whether the rush could be politically motivated, Ashish Jha, the dean at Brown University School of Health says, “I think it’s almost a certainty” and that November, “feels awfully early.”  

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