‘No guarantee, just hope’: Phase 3 COVID-19 vaccine trials are launching in Arizona – AZCentral

Anna Lunaria says she wouldn't usually consider signing up for clinical trials of new drugs or vaccines.

But last week, shevolunteered to participate in the first late-stageCOVID-19 vaccine trials in Arizona, despite the potential risks as a test subject.

"I'mnot afraid of a vaccine. I'm afraid of the virus," said Lunaria, aPhoenix acupuncturist. "I think of it as my patriotic duty to do what I can in this time."

American biotech company Moderna and American pharmaceutical giant Pfizer both launchedlate-stage trials of their respectivevaccines on Monday. Thevaccines haveemerged at a breakneck speed and haveshown promise in earlier studies.

The federal government has announced a goal of delivering 300 million doses of a safe, effective vaccine for COVID-19 by January 2021in a plan called Operation Warp Speed.

If early results from eithertrial look good, avaccine could be fast-tracked for approval, but it's unclear who would initially receive the vaccine if it's approved.

Four Arizona sites are participating in Moderna's nationwide trial, none affiliated with hospitals or research universities. Threesites are at a private research company calledthe Hope Research Institute, with locations in Chandler, Peoria and Phoenix. The fourth is at the Quality of Life Medical and Research Center, a private health care provider and research center basedin Tucson.

The Phoenix Hope Research Institute location will alsoparticipate inthe Pfizer trial, along with a private clinical research company in Tempe called theClinical Research Consortium.

Bothtrials will enroll 30,000 participantsand are meantto be a final testof the vaccine's safety and effectiveness.

The results are expected to be reviewedby drug regulators like the Food and Drug Administration for potential vaccine approval.

The trials willfollow participants for two years after they are injected as they live their normal lives, with regular check-ups to measure participants' immune system responses. Because of pressure to make a vaccine quickly,it's possible either vaccine could be released well ahead of the formal conclusionof the studies.

Early data from Moderna vaccine trials looks encouraging, company officials said. Vaccinated participants generated more neutralizing antibodies than have been seen in most recovered COVID-19 patients. The study results reflect45 participants, all of whom were under the age of 55 and most of whom were white.

There were some reported side effects in the study, which varied depending on the dosage. While no one who received a mild dose experienced fever, six participants in the moderate dosing group experienced fever, along witheight in the high dosing group, including one who had to be hospitalized.

Pfizer is continuing to collect data from earlier studies but said in a press release that preliminary results based on nearly 120 patientsshowed the vaccine was able to produce antibodies that could neutralize the virusin all patients with generally mild to moderateand temporary side effects such as fever, fatigue and chills.

Earlier data from the first 45 patients showed that the rate of fevergrew more common in patients who received higher doses. After a second dose of the vaccine, 75% of patients in a moderate dosing group experienced fever.

Bill Gruber, the Pfizersenior vice president ofvaccine clinical research and development, declined to give an exact demographic breakdownof early study groups, but said a small percentage of participants were from minority groups.

For some, thesetypes of side effects and study limitations, coupled with the rapid pace of vaccine development, raises concerns.

"Any time that we try to accelerate the discovery process, we run the riskof cutting corners," saidJason Robert, an Arizona State University bioethicist who focuses on how to practice safe and ethical science.

Before signing up for any COVID-19 study, Robertcautions that peopleshould fully understand the risks and shouldn't volunteerfor the wrong reasons.

"Scientists are doing this for the good of the whole, not the individual," he said. "It might be our civic dutyto participate in these studies, but don't do it because you think you're going to get better."

Only some trial participants will receive actual vaccines. Others will receive placebo injections instead, allowingresearchers tocompare the results.

This means if a participant receives a placebo instead of a vaccine, they may be giving up their chance to get a vaccine right away if a vaccine is approved sooner.

Both studies areblinded, meaningparticipants will not know whether they have received the vaccine or the placebo. This is done to avoid any potential bias in the data.

There is some potential risk for participants, said Jack McGettigan, the doctor who is overseeing Moderna's trial in Tucson.If there are any side effects, McGettigan said he expects to see mild fevers or body aches,which typically disappear quickly.

He hasn't seen indications of significant problems, "butyou don't know until you do the actual study," he said.

He wishes to enroll at least 300 participants at his trial location.

"I'm hopingjust to domy best to get patients in as quick as possible, because the quicker we get them in, the sooner we'll get results," he said.

There's no guarantee the vaccine will be successful, he said. "There's just hope."

Clinical trial participants haven't always reflected broader populationsand have skewed towardhealthier, young white males, but this is something many researchers are trying to change.

For COVID-19 vaccine trials, the FDA has issued guidance that "strongly encourages the enrollment of populations most affected by COVID-19, specifically racial and ethnic minorities," and has encouraged the inclusion of other high-risk groups such as those with underlying diseases in late-stage vaccine trials as well as pregnant women or women of child-bearing age.

The inclusion of these groups can have important implications for understanding how a treatment may affect various groups differently, since genetics or other factors influence how well a treatment works.

A poster is displayed in the entrance way looking for volunteers as the world's biggest study of a possible COVID-19 vaccine, developed by the National Institutes of Health and Moderna Inc., gets underway Monday, July 27, 2020, in Binghamton, N.Y. (AP Photo/Hans Pennink)(Photo: Hans Pennink, AP)

Both trials excludepregnant women and those with certain immune disorders. McGettigan said he is trying to enroll racial minorities and other higher-risk groups for Moderna's trial by reaching out to the Hispanic community and local tribes.

"There's evidence that shows that COVID-19 affects different races differently so it's very important to have strong minority representation in the study," said NathanAlderson, the CEO of the Hope Research Institute.

Enrolling diversepatients can be a challenge, according to Gruber.

"It is somewhat challengingin some instances to get into those communities and there's a lot of work that we're doing to provide a reassurance to those communities about the safety of vaccines," he said.

Of the Arizona sites for both vaccine trials, the Quality of Life Medical Research Center is the only one enrolling Spanish-speaking participants. The rest only accept English-speaking participants.

Towler said he expects to enroll up to 200 participantsat the Clinical Research Consortium trial site; 108 participants have already enrolled.

The Hope Research Institutewill enroll as many eligible participants as possible, first come, first served.

"We're really excited to bring these trials to the Phoenix area and do our part to accelerate these trials towards potential approval," Alderson said."It's astounding to see the industry move this fast."

ASU bioethicist Ben Hurlburt acknowledges that this pandemic is a public health emergency requiring aspeedy response, but said there is a danger in latching on to promising treatments too quickly.

"There's a hunger for answers, fast answers," he said. "There's maybe less attention to the provisionalities and nuances of those answers."

Vaccine development is often a long and complicated processand it typically takes over 10 years to getvaccine approval. Determininglong-term side effects or effectiveness takes years, and researchers must clear many regulatory hurdles.

Some of those hurdles are being taken away, according to Robert. Moderna, for example,was not initially required to do animal model tests of its vaccines before testingin humans.

"That's an example of jumping over a step in the vaccine development process," he said. "That could be potentially problematic."

Some researchers argue that speeding up the process is necessary.

"This is apandemic of unprecedented magnitude that we haven't seen for a hundred years or so. Wedon't want to sit around and pontificate," McGettigan said.

Gruber saidthe notion that drug or vaccine developers are cutting corners is a misconception, and attributes the speed to greater regulatory efficiency.

Where it used to take months to get studies reviewed for approval, he said, it now takes days.

He said Pfizer is still using the same criteria in its development process, which is why initial vaccine trials were only tested in a small number of people to check for safety before moving onto larger tests.

McGettigan also argues that the science behind making vaccines has accelerated rapidly, allowing researchers to move quicker than ever before.

BothModerna's and Pfizer'scandidates are a new type of vaccine. Traditional vaccines rely on injecting patients with inactivated virusor some other agent that resembles the virusto help train the body's immune system to recognize the virus's shapeand develop antibodies to neutralize it.

The world's biggest COVID-19 vaccine test got underway Monday with the first of 30,000 planned volunteers. The experimental vaccine is made by the National Institutes of Health and Moderna Inc. It's one of several candidates in the vaccine race. (July 27) AP Domestic

The Moderna and Pfizer vaccines are mRNA vaccines, meaning they relyon injecting patients with parts of the virus's genetic code, known as RNA.

Each company'sCOVID-19 vaccine focuses on the part of the virus's genetic code that is responsible for creating the spikes on the outside of the virus that allowit to infect cells. When injected into a patient, the genetic codeacts like a set of instructions given to the host cell and causes the host cellto start producing the spikes, but not the rest of the virus.

In this form, with just the spikes, the virus is not infectious, but in theory, the presence of the spikes will stilltrain the immune system to recognize and fight future COVID-19 infections.

Such vaccines are easier and quicker to produce than traditional vaccines, buthave never been approved for use by the FDA.

"The beauty of them is that they can make a lot of vaccine much more quickly thanthe old techniques. The biggest downside right now is ithas not ever been proven to be an effective vaccine because it's so new," McGettigan said.

Even if its vaccine is approved,Pfizer will continue to tweak itto improve safety and efficacy, according to Gruber. Pfizer will try to lower the dosage needed to get protection, he said.

"This could be a watershed moment not just for COVID-19 but this could be applied for other pathogens," he said, explaining that Pfizer is also testing this approach for the influenza vaccine.

Earlier this month, the U.S. governmentagreed to payPfizer $1.95 billion to secure 100 million doses of the vaccine that can be given to the public for free if it is approved.

While Pfizer isa well-established pharmaceutical giant, Moderna was a relatively new, unknown company and hadnever developed an FDA-approved drug. Modernahas received nearly $1 billion from the federal government for its vaccine development efforts.

The Moderna mRNA vaccine does not cause any more reactions than many already-licensed vaccines,according to the National Institute of Allergy and Infectious Diseases, which said the side effects are "mild or moderate."

Another big question that needs to be answered is whether antibodies provide long-term immunity, Alderson said. If they don't, it'spossible that vaccines will need to be administered annually.

"There's no good datato show how long antibodies will last," he said.

It's not just about antibodies though, according to Gruber. Other immune cells, such as memory T-cells, which are trained to recognize viruses, can be important for long-term immunity, which is why Pfizer is also measuring the levels of these cells in trial participants.

So far, he said Pfizer is seeing a robust immune system response to their vaccineand has measured good response levels of other cells such asmemory T-cells.

That'sbecause Pfizer is using a large section of the virus'genetic code in their vaccine, he said, which can have important implications for broad-spectrum protection.

"We have more potential parts ...for the immune system to recognize," he said. "Given that not all of us recognize every little piece of a foreign agent like a virus, this maximizes our potential, across adiversity of racial and ethnic groups, ages, and geographical locations, that we'llbe more likely to provide protection."

The National Institute of Allergy and Infectious Diseases said that "durability of protection will have to be answered experimentally," and addedthat the possibility of the virus mutating in a way that renders a vaccine ineffective in the long term is not a current concern.

McGettigan said not everyone is a good fit for research, but heconsiders those who are volunteering to be medical heroes.

"They are willing to take a risk," he said. "It's a lot of altruism. There are people who are willing to step up for their fellow humans and take the first shot."

One such potential volunteer is Natarajan Ganesan,a biomedical researcher who has previously worked with the infectious diseases institute. As a former researcher, Ganesan has no illusions about the vaccine and is aware of the risks.

"Is it promising? I won't say that, but I won't play it down either," he said. "Phase three is really when the rubber meets the road and when we really get to test the vaccine."

Even with the unknowns, study locations say they are taking steps to make trials as safe as possible, and both trialsare monitoring for serious side effects in real time.

This allowsstudies to be shut down quickly across all locations if there is a cause for concern.

The intense monitoring of side effectsmakes Phoenix resident Candice Fremouw sometimes feel more comfortable with clinical studies than treatments at the doctor's office.

Fremouw says she has participated in six studies in the past, including vaccine studies, andhas now signed up as a potential volunteer for the Moderna trials.

"I feel comfortable," she said. "They're so tightly supervised."

Gruber said the Pfizer trials will be extremely rigorous in checking for side effects, but that he isn't worried.

"I think there is essentially a zero chance that we would be seeing any untoward safety events that would slow us down," he said. "But that doesn't keep us from looking really hard to make sure we don't miss one."

Fremouw is confident in the trials because she has takennew vaccines in the past.

"I remember standing in line for sugar cubes for polio," said Fremouw, who's 64 and retired."We've done this before."

Even if a vaccine turns out to be safe and effective, Robertsayspeople should approach study results with cautionandhold off on making any travel plans on the promise of a vaccine byspring.

With many people desperate for a cure andcompanies vying for the spotlight and money that comes with producing a successful vaccine, he said it can be easy to over-hype the promise of any vaccine.

"This is a process, and it's a marathon, not a sprint," Robert said. "A safe and effective vaccine isn't necessarily going to be the be all and end all of this."

It's still unclear whether a vaccine will provide long-term immunity or whether different vaccines will be needed for different strains of the new coronavirus.

FDA guidelines state that vaccines should aim to be at least 50% moreeffective in providing protection compared toa non-vaccinated personto "ensure that a widely deployed COVID-19 vaccine is effective."

The FDA did not respond to further questions about the vaccine approval process, but Gruber saidPfizerexpects to be able to show over 50% efficacy by October. He said thetimeline could be affected if the pandemic slows down and there is less enrollment as a result.

It's still possible for both vaccines to fail. If that happens, the vaccines may never hit the market. The window of success can be small, Towler said.

Pressure to create a coronavirus vaccine is increasing by the day, but for a safe vaccine to enter the market, it takes time. USA TODAY

Still, Towler remains optimistic that someone will succeed with so many different companies and researchers working toward this goal.

"They will have something that comes through with positive results," he said. "We're not just hedging our bets on one option."

There also may be manufacturing and distribution issues that slow down the goal of herd immunity.

Modernahas saidit is on track to manufacture and deliver500 millionto 1 billion doses of the vaccine per year, but people may need two doses of thevaccine for it to be fully effective, so not everyone will be able to receive it right away.

In a press release this week, Pfizer saidthe company is on track to seek regulatory review "as early as October 2020" and that if the vaccine gets approved, they could supply up to 100 million doses by the end of 2020 and approximately 1.3 billion doses by the end of 2021.

If the vaccine is approved, it's unclear who would get itfirst. Modernaand the FDA did not respond to questions about the process, but Gruber said that will be a decision that is left up to government agencies. He said he suspects that frontline workers, essential workers, older individuals and those at greater risk will be seriously considered for earlier access to vaccines.

To complicate the goal of herd immunity further, a poll fromThe Associated Press-NORC Center for Public Affairs Research found that 20% of respondents would refuse to take a vaccine if oneis approved, and another 31% were unsure.

Anti-vaccination sentiment is part of what pushed Lunaria to volunteer for trials.

"In this time when so many people are so crazy about science and vaccines, people like me need to walk our talk," she said.

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'No guarantee, just hope': Phase 3 COVID-19 vaccine trials are launching in Arizona - AZCentral