Get the Latest on COVID-19 Vaccine Research in MichiganSeptember 21, 2020
Of the eight vaccines under development in the U.S. and more than 40 in human trials worldwide, Michigan has three Phase 3 clinical trials on humans underway at Michigan Medicine (AstraZeneca) in Ann Arbor, Henry Ford Health System (Moderna) in Detroit and the Michigan Center for Medical Research (Pfizer) in Farmington Hills.
Henry Ford Health also expects to begin enrollment in a fourth clinical trial in Michigan for a coronavirus vaccine with Johnson & Johnson in October, officials said.
Early research on the AstraZeneca, Moderna and Pfizer vaccines have shown success in stimulating neutralizing antibodies in small numbers of test subjects, the companies have said.
But it’s unclear how strong or how long the antibodies will last to fight the coronavirus. Each COVID-19 study will last two years, but data and regulatory approval could be sought earlier if the vaccine is proven effective, experts said.
Daniel Kaul, M.D., a vaccine researcher and infectious disease doctor with Michigan Medicine, said AstraZeneca authorized Michigan Medicine to enroll at least 500 people into the study, and nearly all those slots were taken before a safety pause was put into place. Nearly 4,700 people have expressed interest to Michigan Medicine in the study.
“It’s what’s called a competitive enrollment, so as long as you’re doing everything properly, and they keep a very close eye on it, you can keep enrolling to 1,000 or 1,500,” Kaul said.
Earlier this month, however, U.S. researchers in the AstraZeneca trial stopped enrolling patients at about 90 test sites because the British drug company temporarily halted the study after a 37-year-old woman in England developed a neurological problem in her spinal cord after a fall. The volunteer, who had no pre-existing conditions, reportedly has been discharged from a hospital.
While health authorities have allowed AstraZeneca to resume dosing volunteers with the vaccine in the United Kingdom and Brazil, the FDA hasn’t decided whether to allow trials to continue in the U.S. A top official at the National Institutes of Health said the agency is “very concerned” about the complication and has launched an investigation, which could take several weeks, according to Kaiser News.
“We were going to start dosing (Sept. 11),” said Kaul, adding it would take about 48 hours to restart the trial at Michigan Medicine. “We are just waiting for guidance to begin. I am sort of heartened by this process. The last thing anyone wants to do is continue a trial when it is not safe, but you can’t give up on it when an event happens with one person.”
The AstraZeneca vaccione is different than those from Moderna and Pfizer because it uses a modified and weakened version of a chimpanzee common-cold adenovirus. The virus has been tweaked to contain the genetic spike protein found in SARS-CoV-2.
The Moderna and Pfizer test vaccines use messenger RNA, a copy of the SARS-CoV-2 genetic code, to trick the body into creating COVID-19 antibodies to fight off infection.
Jay Jagannathan, M.D., a neurosurgeon in Troy who is familiar with research studies, said it is not unusual for vaccine test subjects do develop neurological problems on rare occasions. He said vaccine research typically leads to about three cases per year of transverse myelitis, where the immune system attacks the spinal cord, which is what has been reported to be the problem with the AstraZeneca subject.
“It can result in mild problems in the arms to complete paralysis,” Jagannathan said. “It is concerning and warrants more scrutiny. AstraZeneca was very tight-lipped about the patient. More information needs to be released.”
Besides the mystery surrounding the AstraZeneca trial, other questions have arisen about COVID-19 vaccine research.
One is whether there are enough people of color, especially Black people, volunteering for the clinical research trials to show the vaccines are effective across demographic groups.
Doctors at the three COVID-19 test sites in Michigan declined to state the percentage of minority participation they have recruited into the trials, although they say outreach to minority communities has been intense.
Only Moderna has given out statistics on minority participation in the COVID-19 trial. Of the 23,497 participants enrolled so far nationally, 27 percent of participants are from minority groups, Moderna said. NIH data for 2019 shows that 30 percent of research participants are from minority groups.
Paul Kilgore, M.D., a Henry Ford senior researcher and co-principal investigator in the Moderna trial, said more than 10,000 people applied for the Moderna trial. He declined to give local enrollment numbers, citing Moderna rules.
“Each person that becomes enrolled at that first visit are administered the first dose. … Everything is going well and we are now moving into the second dose,” Kilgore said.
Under the COVID-19 trials, volunteers are usually given two shots, one month apart, and then are monitored with blood tests and regular check-ups over two years. Preliminary data could be available sooner, depending on vaccine effectiveness and the COVID-19 incidence rate in the community, experts said.
So far, side effects of the test vaccines have been mild, including fatigue, chills, headache or muscle pain, especially at the first lower-dose injection, said the New England Journal of Medicine. Some people reported fever after getting the second, larger vaccine dose.
Experts have expressed concern about the speed of the vaccine trials because of the need to create “herd immunity” in the population to slow the infection rate, but Katzman said he believes an interim analysis on the Pfizer vaccine data could be completed soon that could show whether it has produced sufficient protective antibodies against the coronavirus.
“The safety is great so far. It is always a concern. We have never had a vaccine developed so fast, but we have a pandemic and everything is being fast-tracked,” Katzman said. “It is important to see an antibody response (even if it is weak). If people receive the vaccine and contract COVID, they will be able to fight the virus much easier and will have a much less severe case.”
Last week, Pfizer CEO Albert Bourla said that by the end of October, the company should have sufficient data to show its vaccine is safe and effective. Pfizer is planning to provide 100 million doses of a vaccine by the end of the year and 1.2 billion doses in 2021.
Pfizer also is preparing a manufacturing facility in Kalamazoo to make the shots under the federal government’s Operation Warp Speed. The U.S. has promised several drug companies billions of dollars to purchase up to eight vaccines and 300 million doses if they work.
But one safeguard built into the U.S. drug research system is that the FDA relies on the Data Safety Monitoring Board, an independent group of experts, to issue recommendations on drug and vaccine safety. Vaccines are much different than normal drug approvals because vaccines are given to healthy people, experts say.
Kilgore said several factors go into decisions whether to approve an early release of a COVID-19 vaccine, including the incidence rate of the disease in the community and in the trial group. The more common the disease is, the easier it is to measure how well the vaccine might be protecting people.
Statistically speaking, Kilgore said, “It becomes easier to reach a vaccine efficacy (effectiveness) measurement and reach it faster when the incidence rate is higher.”
Michigan researchers say COVID-19 vaccine development so far has been promising.
Despite the one reported negative reaction, a study published recently in The Lancet confirmed a single dose of AstraZeneca AZD1222 vaccine resulted in a four-fold increase in antibodies to the SARS-CoV-2 virus spike protein in 95 percent of participants one month after injection.
“Clearly, (the FDA is) is going to want to see safety that they’re satisfied with and they want to see efficacy (effectiveness) is at least 50 percent,” Kaul said.
“What that means is you give (the vaccine) to 30,000 people and over the next two months 200 people get symptomatic COVID in the placebo group and 100 get symptomatic COVID in the vaccine group. Then you’d say the vaccine effectiveness is 50 percent,” Kaul said.
The FDA could approve a vaccine for certain populations and ask for additional follow-up data on other subgroups after initial approval, Kaul said.
“Because of shortages (of vaccine production) and early approval, it may be approved for certain populations at first” to stretch supplies, Kaul said.
Katzman said he expects first responders such as health care workers, paramedics, police and firefighters will be first in line to receive the vaccine, which will be in very limited supply until next year.
“After that, nursing, group homes and higher risk individuals, but it is tricky because they have health conditions,” Katzman said.
*Originally published in Crain’s Detroit Business.