The J&J Vaccine at the FDA

 By Derek Lowe 

The briefing documents are out at the FDA site for Friday’s hearing on the J&J vaccine. Here’s a summary at STAT from Matthew Herper and Helen Branswell, and I agree with their take: overall, the numbers look good. Update: here’s a good Twitter thread from Hilda Bastian, and here’s one from Eric Topol.

Like every other vaccine that we’ve seen the clinical data on, this one also seems to completely prevent deaths from the coronavirus. I might be mistaken, but so far I don’t think we’ve seen a single SARS-Cov-2 fatality in the treatment group of any of the Phase III trials. As for severe disease, this one had a strong effect as well, but it might take a bit to kick in completely. 14 days after the single dose, there were 29 people hospitalized with coronavirus in the placebo group and only 2 in the treatment group, but if you look at the 28-day mark there were zero hospitalizations at all.

This makes one think that the full protective effect might be coming on a bit more slowly than the Pfizer/BioNTech and Moderna vaccines, but making cross-trial comparisons like that is risky. The coronavirus landscape has changed since the earlier vaccines, and you can see some of that in the way that the J&J data break out their South African trial. Overall vaccine efficacy was 72% in the US versus 58% in South Africa, where there’s been a lot more B.1.351 variant circulating. But they also have data from Brazil, where the P.2 variant there doesn’t seem to have made much of a difference, and the B.1.1.7 variant first noted in the UK doesn’t seem to be a problem, either.

What about protection against asymptomatic infection? Of the roughly 10,000 people in the treatment arm of the trial, 2892 of them were tested with or without symptoms for signs of coronavirus infection. The FDA’s take on the data (see numbered page 35 of this document) is that there is weak-to-no evidence of such protection out to day 29, and around 60 to 70% efficacy in the post day-29 data. Like the other trials, it seems very likely that all of this will also reduce transmission of the virus, although the study isn’t designed to track that specifically. We’re getting reports from Israel and the UK, though, that would seem to confirm this. I would be very surprised if the levels of efficacy we’ve been seeing didn’t have a strong effect on transmission, but you have to get the numbers to be sure, and I’m glad that those are starting to show up.

There’s a lengthy discussion of subgroups in the treatment groups (starting on numbered page 27 of this document), but what I get out of that is that there aren’t any huge differences. I’ve seen a couple of mentions this morning of lower efficacy against severe disease in >60 year old patients (see that document’s Table 16 on page 32), but the FDA document points out that this may be an artifact of only including cases that were confirmed at the trial’s central location by the time of the data cutoff. Looking at the overall numbers, the older patients look much more similar to the other cohorts, at around 75% VE against severe disease.

Now, about overall efficacy. It’s easy to look at the figures and say “Hey, that’s fine, but it’s not up to what Moderna and Pfizer/BioNTech showed”. That still might be true, but we don’t know what those latter two would have shown if they’d been run at the same time as the J&J trial. It’s also tempting to look at the J&J adenovirus vaccine and the Oxford/AZ adenovirus vaccine and decide that adenovirus vectors are a step behind the mRNA technology, but for the same reasons, we can’t be sure that’s right. Note that the Gamaleya Institute vaccine in Russia posted better numbers, for one thing. And the differences between the three adenovirus vector vaccines themselves are pretty significant: J&J’s data are for one shot of an Ad26 vector (a two-shot trial is still running), and their sequence has the stabilizing protein mutations in the Spike. Oxford/AZ is a different adenovirus (from the chimpanzee population), and their sequence is wild-type Spike without the stabilization. And then Gamaleya is a two-shot regimen, one with Ad5 and the other with Ad26, with the Spike mutations. Update: it’s not clear, actually, if that one does, so for the time being we’ll assume that it’s just wild-type Spike. (Both mRNA vaccines have the stabilizing mutations as well, for the record).

So while we can’t avoid trying to compare all these, we also have to realize that between the fundamental differences and the differences in the timing and locations of the trials, that our comparisons have a substantial chance of being off to some degree. What have we done in the past when we have had such comparisons to make? Good question! But we’ve never had a situation like this, where a whole list of different vaccines, many from completely different platforms, have been rolled out so quickly against the same evolving pathogen. So it’s not like there’s a standard playbook for all this. If we never see this sort of thing again, by the way, that’ll be just fine with me, considering what conditions cause it to happen.

So this vaccine looks certain to get Emergency Use Authorization in the US, and by the time we get on into April it should start making a difference in the vaccinated-population numbers. Production has been slower than J&J were estimating at first, although it now looks a bit better than their more pessimistic estimates. As detailed here, adenovirus vector production is yet another art form, and anything with a big cell culture step in the middle of it has the potential to act up (and for reasons that can be quite difficult to figure out).

But the big message is the same: right now, variants and all, we’re winning. The vaccines work, there is a whole list of them, and their production is increasing while we watch. The countries that have gotten off to faster starts vaccinating their populations are already seeing the effects, and no bad safety signals are yet complicating things. Nor are we seeing evidence so far of antibody-dependent enhancement (worse infections recurring in people who have already been vaccinated). If we can keep this pressure up and keep ramping up vaccine supplies and their rollout around the world, we are going to beat this virus. Good riddance to it.

https://blogs.sciencemag.org/pipeline/archives/2021/02/24/the-jj-vaccine-at-the-fda

Homeless, Foster and Jailed NY Teens Now Eligible for COVID Vaccine

 New Yorkers 16 and older in juvenile detention, youth shelters and foster care facilities can now receive the COVID-19 vaccine, according to new guidance from the Cuomo administration.

The Office of Children and Family Services sent a letter to provider agencies Monday night emphasizing that older teens in residential programs licensed or certified by the state are eligible for vaccine distribution.

The memo is an attempt to clear up confusion that has existed for the past few weeks over whether kids in juvenile facilities could get a dose.

“Our document yesterday clarifies to providers that the [state Department of Health] guidance from February 15 opens the vaccine prioritization for youth in congregate settings,” Melissa Mahaffey, an Office of Children and Family Services spokesperson, said in an email to THE CITY.

While questions about consent still linger, an Administration for Children’s Services spokesperson called the move “a game-changer.”

“Just as we did for frontline staff, we have been advocating for eligibility to be expanded to youth in our congregate facilities, and we’re pleased that the state has heeded this request,” said the spokesperson, Marisa Kaufman.

About 636 eligible kids are in ACS facilities, she said. About the same number of teens over 16 are in youth homeless shelters, according to the city’s Department of Youth and Community Development.

The Pfizer vaccine can be used for those 16 years of age and older, while the Moderna vaccine is for adults 18 and up, according to the state’s guidance, which cites the FDA.

Confusion and Inaction

January guidance from the state child welfare agency focused only on vaccination for staff, and the wording in the Feb. 15 memo did not make it clear that teens could be included, lawmakers and advocates say.

On Feb. 9, Dawne Mitchell of The Legal Aid Society — the city’s largest public defender organization — issued a letter to Office of Children and Family Services Commissioner Sheila Poole urging the agency “to amend the OCFS guidance to allow these young people age 16 and older to receive the vaccine.”

In a Feb. 19 letter to Poole, State Senator Brad Hoylman (D-Manhattan) pointed out how “a 19-year-old residing in an adult homeless shelter would be eligible for the vaccine now, but if that same 19-year-old was residing in a [homeless youth] facility, they would not be eligible.”

Advocates for homeless youth say the confusion and resulting delay was unnecessary — and that the kids should have been explicitly prioritized from the start.

“Why is this population always an afterthought that needs additional advocacy?” asked Jamie Powlovich, executive director of the Coalition for Homeless Youth. “For a long time NYC has taken this position of quite frankly gaslighting the needs and the reality of what is and isn’t given to youth experiencing homelessness in this city.”

In her letter, Mitchell noted children in these settings are continually going through disruptive quarantining, and experience higher rates of adverse health conditions that can lead to COVID-19 complications.

The Horizon Juvenile Center in The Bronx, Nov. 12, 2020.

 Hiram Alejandro Durán/THE CITY

Mitchell also noted that Black and Hispanic children and young adults make up the majority of youth held in OCFS-overseen facilities — populations that have both borne the brunt of the COVID-19 pandemic and vaccine distribution inequities.

At a Friday City Council hearing, legislators questioned child welfare officials on COVID-19’s effect on juvenile justice facilities.

Administration for Children’s Services officials testified that 17 children in juvenile detention have tested positive for the virus since last March.

More than 40 detention center staff have contracted the virus, Darek Robinson, vice president of grievances and legal services at SSEU Local 371, the union that serves many ACS workers, told the Council hearing.

ACS officials said that four of those workers have died.

At the peak of the pandemic, many young detainees were released following a Legal Aid lawsuit which cited reporting by THE CITY.

“It’s unrealistic to think that you can socially distance,” Robinson told THE CITY on Tuesday, noting that the coronavirus typically enters facilities via adult staffers.

“It’s a great, great thing that youth [will] receive their vaccines to help prevent the spread of the virus.”

More Complications to Navigate

For youth now eligible for vaccines, a shot won’t necessarily come quickly. For anyone under 18, providers will be grappling with complicated issues of consent.

“Young people’s relationship to legal guardians, whether their birth parents or other, you know, other guardians in their lives really vary,” said Powlovich.

Kaufman said that “written, informed parental consent” will be needed for children under 18 to get a vaccine, with certain exceptions for anyone pregnant or parenting and foster kids who are freed for adoption.

She added, “While routine care vaccines do not require parental consent for most youth in ACS’s care, we do not think that these can yet be considered as part of routine care.”

According to the city Department of Youth and Community Development, which oversees homeless youth shelters, the agency will work with providers to help with vaccination efforts, but did not specify how.

“At this time, DYCD has not heard of plans” for vaccination sites at homeless youth shelters, Mark Zustovich, an agency spokesperson, told THE CITY Tuesday in a written statement.

Despite clear speed bumps ahead, Hoylman said that he was “heartened that among young people there isn’t vaccine hesitancy as much as there’s vaccine impatience.”

“And that’s a good sign in the months ahead as we expand the vaccine to younger parts of our population.”

Redmond Haskins, spokesperson for The Legal Aid Society, said lawyers cheered the news that their young clients now have access to the vaccine — but questioned why adult prisoners were still excluded.

“COVID-19 still rages at these facilities throughout the state, and any further delay will only result in more infections and more loss of life. We urge Governor Cuomo to grant this essential relief now.”

https://www.thecity.nyc/2021/2/23/22298338/new-yorks-homeless-foster-and-jailed-teens-now-eligible-for-covid-vaccine

U.S. could reach herd immunity by late spring

 The United States could be approaching herd immunity, which occurs when enough people become immune to a disease to make its spread unlikely, according to Suzanne Judd, Ph.D., an epidemiologist in the School of Public Health at the University of Alabama at Birmingham.

Based on the number of vaccinations that have already been administered, as well as findings from a recent study by Columbia University, Judd estimates the nation may reach herd immunity by May. The study by Columbia suggests that, as of the end of January, more than a third of the U.S. population had already been infected with coronavirus.  

Scientists believe 72 percent of the population needs to be either exposed or vaccinated for COVID-19 in order to reach this goal.  

For Alabama, that means 3.5 million people need to have immunity.

“Three factors determine how quickly Alabama can get to 3.5 million people with immunity: number of people with a positive test, number of people who were infected with COVID but never had a positive test, and the number of people vaccinated,” Judd said. “We have great data to know how many people tested positive and how many people have been vaccinated. From there, we can estimate how many people have immunity but never received a vaccine and never had a positive test based on studies that have tested immunity in blood. We are able to put these numbers together and come up with the estimate of when we will reach herd immunity, which is May of this year.”  

What happens when we reach herd immunity? 

“It means that cases decrease without social intervention, which might be what we are starting to see right now,” Judd said.  

Even though the data are hopeful, it does not mean COVID-19 will be eradicated or that we can let our guard down when it comes to following social distancing and masking precautions.

“I think that COVID-19 is going to be endemic in the United States,” Judd said. “It is going to be like the seasonal flu, something we have to tolerate regularly. There will be isolated outbreaks, and they will likely occur in populations with lower immunity. This means that, just like the flu, a strong vaccination campaign will be needed to keep people out of the hospital.”

Suzanne Judd, Ph.D.Another positive trend that shows the reduction of the severity of COVID-19 cases is the decrease in the number of hospitalizations and deaths.

“We are seeing sharp declines in the hospitalization ratio in the last month and a half, likely driven by monoclonal antibody therapy, but possibly also driven by the vaccine,” Judd said. “If people are vaccinated and still become infected, the case may be milder than it would have been if they were not vaccinated, which leads to lower hospitalizations.”

While the production of the vaccine is increasing, there are still millions of people who do not have access to it. To reach herd immunity, Judd says the vaccine needs to be available to every community.

“We need to get consistent vaccine administration to lots of different populations” Judd said. “We cannot leave people behind. We have to make sure the vaccine is getting into all communities to get that base level of immunity to stop the virus from spreading.”  

https://www.uab.edu/news/research/item/11866-u-s-could-reach-herd-immunity-by-late-spring

Senate eyes paring back Biden's $1.9 trillion COVID-19 aid plan

 U.S. senators on Wednesday were eyeing potentially significant cuts to President Joe Biden’s $1.9 trillion COVID-19 relief bill as they awaited a ruling on whether the measure can include raising the federal minimum wage to $15 an hour.

The Senate parliamentarian was expected to decide soon whether Senator Bernie Sanders’ proposed minimum wage increase is allowable under a rule allowing a simple majority of the 100-member Senate to approve the sweeping relief measure, instead of the chamber’s typical 60-vote majority.

The House of Representatives on Friday could pass the bill that would help tackle the heavy human and economic toll of the COVID-19 pandemic, which has killed more than 500,000 Americans and thrown millions out of work.

The Senate is likely to follow up in early March. The measure is Biden’s top legislative priority.

Senate Democrats and Republicans were looking at scaling back some of the biggest provisions, including expanded federal unemployment benefits, $1,400 direct payments to Americans and money for state and local governments, according to lawmakers and aides.

Some rural-state senators hoped that such cost cuts could create savings to be used to improve their lagging broadband service.

According to a Senate aide familiar with private conversations, various senators mulled tying additional federal unemployment benefits to individual states’ jobless rates.

A new round of stimulus checks could be scaled back to exclude more high earners, the aide said. Several senators, including Democrat Joe Manchin, have said they were looking at a minimum wage increase to $10 to $11 an hour, instead of $15 by 2025, up from the current $7.25.

“I think even though several Democrats have some concerns, that we can still find a basis for agreement,” Dick Durbin, the No. 2 Senate Democrat, told reporters.

Democratic Senate Majority Leader Chuck Schumer, who must juggle demands of progressive and moderate Democrats amid Republican opposition, described a U.S. economy in need of help beyond the nearly $4 trillion provided last year.

“Our country is still in the throes of crisis,” Schumer said in a Senate speech on Wednesday. “Millions of Americans have reported being thousands of dollars behind on rent, on utilities. Small businesses are hanging on for dear life.”

Senate Republican leader Mitch McConnell acknowledged some families were still struggling, but surveyed a different landscape, citing strong retail sales and brisk manufacturing activity.

“Our country does not need another massive fire hose of borrowed money,” McConnell said.

Over 150 business leaders affiliated with the Partnership for New York City, urged Congress to pass the bill, saying in an open letter: "More must be done to put the country on a trajectory for a strong, durable recovery." here

https://www.reuters.com/article/us-health-coronavirus-usa-congress/u-s-senators-weigh-paring-back-bidens-1-9-trillion-covid-19-aid-plan-idUSKBN2AO2UQ

FDA Staff Find Few Faults With J&J COVID Vaccine

 Johnson & Johnson's one-dose COVID-19 vaccine candidate seemed to meet criteria for emergency use authorization, according to FDA briefing documents released on Wednesday.

On Friday, Johnson & Johnson's vaccine, Ad26.COV2.S, which uses an adenovirus vector for SARS-CoV-2 genetic elements, will be reviewed by the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC). This is the third COVID-19 vaccine candidate slated for review, as VRBPAC previously gave favorable recommendations to the Pfizer/BioNTech and Moderna vaccines, both of which were granted emergency authorization in December.

Similar to the previous two meetings, VRBPAC will decide whether, based on the totality of scientific evidence, the benefits of this vaccine outweigh the risks for adults ages 18 and older.

Based on the briefing documents, FDA technical staff found limited issues with the vaccine's efficacy or safety. Johnson & Johnson's phase III trial was dubbed "Study 3001," and included 43,783 participants in the U.S., Latin America, and South Africa randomized 1:1 to receive the active vaccine or placebo.

Notably, the co-primary endpoints of moderate to severe COVID-19 at 14 and 28 days following vaccination differed slightly from Pfizer and Moderna. Moderate COVID was defined as a positive PCR test plus at least one of the following: evidence of pneumonia, deep vein thrombosis, shortness of breath or abnormal blood oxygen saturation above 93% or respiratory rate ≥20 bpm; or two or more systemic symptoms suggestive of COVID-19. Moderna and Pfizer defined cases more liberally; a cough plus positive PCR test was enough to count toward the primary endpoints.

Topline data was released by the manufacturer and NIAID, which partially funded the trial, on Jan. 29, though it has yet to be published in a peer-reviewed journal. Data reviewed by FDA technical staff found 66.9% efficacy (95% CI 59.0%-73.4%) against moderate to severe COVID-19 at 14 days and 66.1% (95% CI 55.0-74.8%) at 28 days following vaccination.

Buried in the middle of page 38 was vaccine efficacy in the U.S., which was 74.4% at 14 days following vaccination and 72% at 28 days following vaccination.

Vaccine efficacy against severe COVID-19 for the entire cohort was 76.7% (95% CI 54.6%-89.1%) 14 days after vaccination and 85.4% (95% CI 54.2%-96.9%) at least 28 days after vaccination. A post-hoc analysis found two COVID-related hospitalizations in the vaccine group and 29 in the placebo group after 14 days, with 0 and 16 cases after 28 days, respectively.

FDA technical staff noted that efficacy estimates were lower among adults ages 60 and older with comorbidities, though confidence intervals across subgroups "generally overlapped" and efficacy estimates in older participants with comorbidities increased with the number of cases in the analysis. Two hospitalizations in the vaccine group 14 days after vaccination occurred in participants older than age 60 with comorbidities.

The vaccine had lower efficacy in South Africa (52% after 14 days, and 64% after 28 days). Researchers sequenced 72% of the strains in primary efficacy analyses and found nearly all strains in South Africa were from the B.1.351 variant. There were no cases involving the Brazilian (P.1) or U.K. (B.1.1.7) variants in the trial.

Overall, the mean age of study participants was 51, while 55% were men and two-thirds were ages 18-59. About 59% were white, with 45% of Hispanic or Latino ethnicity, and 44% were from the U.S. About 40% had one or more comorbidities.

In terms of safety, injection site pain was the most common local adverse reaction in the vaccine group (49%), while headache (39%) and fatigue (38%) were the most common systemic reactions. As with other vaccines, these were reported more frequently by younger participants.

FDA technical staff analyzed imbalances in adverse events of clinical interest and concluded that a numerical imbalance in events of arthritis and peripheral neuropathy potentially represented vaccine reactogenicity. An imbalance in urticaria (five events in the vaccine group vs one in the placebo group within 7 days of vaccination) was determined to be "possibly" related to the vaccine based on temporal association and biologic plausibility.

However, there was insufficient evidence to determine casual relationships to the vaccine for vaccine versus placebo imbalances in thromboembolic events (15 vs 0, respectively) and tinnitus (6 vs 0), FDA technical staff said.

Three of seven serious adverse events in the vaccine group were considered vaccine-related, including one hypersensitivity reaction not classified as anaphylaxis, one severe injection site pain, and one severe systemic reactogenicity.

As of Jan. 22, 19 deaths were reported -- three in the vaccine group and 16 in the placebo group. Two deaths in the vaccine group were secondary to respiratory infections unrelated to COVID-19, and one was in a participant with HIV. The third died of unknown causes after waking up with shortness of breath.

Johnson & Johnson included a plan for continuing follow-up, which had been an issue at the other two COVID-19 vaccine advisory committees, allowing all participants who received placebo to receive the vaccine when permissible but remain in the trial.

There are currently insufficient data to make determinations about safety in children, pregnant women, and immunocompromised individuals, FDA technical staff noted.

https://www.medpagetoday.com/infectiousdisease/covid19/91343

Does Pfizer's COVID Vaccine Protect Against Asymptomatic Infection?

 Pfizer/BioNTech's COVID-19 vaccine appeared to prevent not only symptomatic disease, but asymptomatic infection as well, a real-world review of Israeli health records showed.

A large case-control study comprising over one million people found that the estimated vaccine effectiveness for "documented infection" was 46% (95% CI 40-51%) at days 14-20 following one dose of vaccine, and was 92% (95% CI 88-95%) at least 7 days following the second dose, reported Ran Balicer, MD, PhD, of Clalit Health Services in Tel Aviv, and colleagues.

Using a proxy for asymptomatic infection, they estimated 29% vaccine efficacy (95% CI 17-39%) at days 14-20 following the first dose and 90% (95% CI 83-94%) at 7 or more days after the second dose, as noted in the New England Journal of Medicine.

Study authors defined asymptomatic infection as "a PCR-confirmed infection with no report of symptoms during referral and initial physician questioning." They included these data in a supplemental appendix, with a caveat: "In the absence of systematic periodic testing of SARS-CoV-2 among asymptomatic people in Israel, documented asymptomatic infections do not account for all asymptomatic infections, and likely cannot capture vaccine effectiveness for this outcome," Balicer and colleagues wrote.

The Pfizer vaccine is authorized in the U.S. to prevent symptomatic COVID-19 illness, which was the primary endpoint in the product's phase III trial. Prevention of overall coronavirus infection was not addressed directly in the trial, though Pfizer promised to examine it later through antibody testing.

Balicer's group also sought to address the vaccine's against the B.1.1.7 "U.K." coronavirus variant, which they said accounted for up to 80% of SARS-CoV-2 isolates in Israel in the days before data extraction. "Although we cannot provide an effectiveness estimate for the B.1.1.7 variant, the plateau observed during the later periods in the cumulative incidence curve for vaccinated persons suggests that the [Pfizer] vaccine is effective for this variant."

Balicer and colleagues examined data from Clalit Health Services, which ensures almost 5 million patients, about half of Israel's population. They attempted to include a population similar to the Pfizer trial: individuals ages 16 and older with no prior positive RT-PCR test for SARS-CoV-2. They excluded healthcare workers, nursing home residents, those medically confined to the home, and those who accessed the healthcare system in the prior 3 days, which may have indicated the start of symptomatic disease.

From December 20, 2020 to February 1, 2021, all newly vaccinated individuals were matched with unvaccinated controls based on variables associated with probability of vaccination or severity of COVID-19.

Overall, 596,618 individuals were matched to unvaccinated controls, who tended to be younger and have fewer chronic conditions. Participants' median age was 45, with an even split between men and women. About 57% had no risk factors according to CDC criteria. About a third were overweight, 17% had hypertension, and 5% had asthma.

Estimated vaccine effectiveness at least 7 days after the second dose was 94% for symptomatic COVID-19 illness, 87% for hospitalization, and 92% for severe COVID-19. For COVID-19-related death, estimated vaccine effectiveness was 72% at 14 to 20 days after the first dose.

Researchers said their large sample size allowed them to estimate vaccine effectiveness in subpopulations that the randomized trial "was not sufficiently powered to evaluate." Across age groups, they found that the estimated efficacy of the COVID-19 vaccine was 94%-96% 7 days or more after the second dose, with similar effectiveness for adults ages 70 and older and younger age groups during the same time period. They also found that vaccine effectiveness may be "slightly lower" among individuals with multiple comorbidities.

They noted limitations to their study, such as excluding healthcare workers and nursing home residents; Pfizer's trial did not exclude healthcare workers. In addition, the date of onset of symptoms was not available, so the date of swab collection was used, though they noted this may be an underestimate of the vaccine effectiveness, since this estimate "reflects a narrower window for the vaccine to be active."

Balicer and colleagues also said the South African virus variant, B.1.351, was rare in Israel during the study period; hence, they were unable to assess vaccine efficacy against it.

Disclosures

One co-author disclosed support from the Morris-Singer Fund.

Primary Source

New England Journal of Medicine

Source Reference: Dagan N, et al "BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting" N Engl J Med 2021; DOI: 10.1056/NEJMoa2101765.

https://www.medpagetoday.com/infectiousdisease/covid19/91350

Moderna Ships Variant-Specific Vaccine Candidate to NIH for Clinical Study

Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, announces that it has completed manufacturing of clinical trial material for its variant-specific vaccine candidate, mRNA-1273.351, against the SARS-CoV-2 variant known as B.1.351 first identified in the Republic of South Africa, and has shipped doses to the National Institutes of Health (NIH) for a Phase 1 clinical trial that will be led and funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The Company also is providing an update on its strategy for addressing SARS-CoV-2 variants of concern.

While initial data confirms that the Moderna COVID-19 Vaccine (mRNA-1273) provides neutralizing activity against variants of concern, out of an abundance of caution, Moderna is pursuing two strategies against these variants, subject to U.S. Food and Drug Administration (FDA) review. First, the Company is evaluating booster doses of vaccine to increase neutralizing immunity against the variants of concern. Moderna plans to evaluate three approaches to boosting, including:

• A variant-specific booster candidate, mRNA-1273.351, based on the B.1.351 variant first identified in the Republic of South Africa, at the 50 µg dose level and lower.

• A multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273, Moderna’s authorized vaccine against ancestral strains, and mRNA-1273.351 in a single vaccine at the 50 µg dose level and lower.

• A third dose of mRNA-1273, the Moderna COVID-19 Vaccine, as a booster at the 50 µg dose level. The Company has already begun dosing this cohort with the booster.

Second, the Company plans to evaluate mRNA-1273.351 and mRNA-1273.211 as a primary vaccination series for those who are seronegative. These candidates will be evaluated in a two-dose series at the 100 µg dose level and lower.

Consistent with the recently updated FDA Guidance for Industry, the Company plans to evaluate immunogenicity and safety in participants who have not received a COVID-19 vaccine as well as participants in clinical studies who previously received the mRNA-1273 vaccine.

NIAID, part of the National Institutes of Health (NIH), will conduct a Phase 1 clinical trial to determine if mRNA-1273.351 can boost immunity against the variants of concern. Moderna will provide doses of mRNA-1273.351 to the NIH. NIAID will initiate this study after receiving safe-to-proceed authorization from the FDA. NIAID will provide additional information when the trial begins, and details will also be available on clinicaltrials.gov. In parallel, the Company will be conducting its own clinical studies to support regulatory filings for any booster vaccine or updated primary vaccine.

https://www.yahoo.com/now/moderna-announces-shipped-variant-specific-211700890.html