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Monday, August 9, 2021

Inovio focused on launching global COVID-19 vaccine trial next month - CEO

 Inovio Pharmaceuticals Inc is focused on launching the global late-stage trial of its COVID-19 vaccine candidate next month, top boss Joseph Kim said in a call on Monday, with the drug developer expecting data in the first half of next year.

In May, Inovio said it would begin the study of INO-4800 in summer this year, after the vaccine candidate was found to be safe as well as well-tolerated and produced an immune response against the new coronavirus in a mid-stage clinical trial.

The company started developing INO-4800 last year, but fell behind rivals after the U.S. Food and Drug Administration (FDA) put a part of the U.S. study on hold for more information on the vaccine delivery device.

The FDA's decision was followed by the U.S. government pulling funding for the late-stage study, citing the fast-moving environment of vaccine development.

The global trial, meanwhile, will initially focus on Latin America, Asia Pacific and regions in Africa, the company said.

"We were initially focusing on Latin America and Asia Pacific, but looking at the rapidly changing vaccination rates and the virus epidemiology, we are including regions in Africa," a company executive said during the post-earnings call.

The company, which has no approved drug in the market, has so far received about $85 million in combined funding from the Coalition for Epidemic Preparedness Innovations (CEPI), the Bill & Melinda Gates Foundation, and the U.S. Department of Defense for the advancement and manufacturing of INO-4800.

Earlier this year, Inovio expanded a partnership with China's Advaccine Biopharmaceuticals to conduct the late-stage trial. Under the expanded deal, the companies expect to equally share its total cost. 

https://www.marketscreener.com/quote/stock/INOVIO-PHARMACEUTICALS-I-17937428/news/Inovio-Pharmaceuticals-focused-on-launching-global-COVID-19-vaccine-trial-next-month-CEO-36115689/

Roche, Abbott COVID Antigen Tests Just So-So in Real-World Data

 Two widely used rapid screening tests for COVID-19, which check for SARS-CoV-2 antigens, missed a significant fraction of infected individuals when used in a real-world setting, researchers reported.

Among 2,215 "all-comers" tested at a German diagnostics lab, with 338 ultimately showing positive results with PCR testing, Roche's SD Biosensor and Abbott's Panbio rapid antigen tests showed overall sensitivities of 60.4% and 56.8%, respectively, reported Christoph Wertenauer, of Synlab GmbH in Augsburg and the University of Heidelberg in Mannheim, and colleagues.

"The sensitivities of the two [rapid diagnostic tests] are unsatisfactory. This calls into question whether their widespread use is effective in the ongoing SARS-CoV-2 pandemic," the group wrote in a manuscript posted to the medRxiv preprint server.

They estimated that if 10,000 asymptomatic people were tested in a population with a 5% true positivity rate, these products would yield 124 false negatives. Testing 10,000 asymptomatic individuals from a population with less COVID-19 prevalence -- 0.5% -- would give 34 false negatives, but a higher rate of false positives (18 in all, or more than one-quarter of all positive results).

"Policy and health care providers should account for substantial limitations of [rapid tests] for SARS-CoV-2," Wertenauer and colleagues noted, especially "in asymptomatic persons. Research into alternative approaches to the screening for SARS-CoV-2 should be intensified."

Previous studies have indicated that rapid antigen tests, which can give results in just a few minutes and in some cases are sold over the counter for at-home use and interpretation, are less sensitive than gold-standard PCR assays that check for viral genetic matter. However, most of these studies had smaller patient numbers and/or were conducted in select samples.

In contrast, the Synlab study analyzed results for individuals presenting for routine testing, and sample collection for both the antigen tests and PCR was performed by trained lab workers.

Most of those tested were referred by physicians (32%) or government health agencies (43%), but the other 25% appeared to seek testing on their own initiative.

Not surprisingly, Wertenauer's group found that positivity rates, both with antigen tests and PCR, were higher in those referred by professionals, presumably because of symptoms or exposure. However, over half the patients tested had no symptoms.

Sensitivities for the antigen tests were especially low -- under 40% -- when the individuals had no comorbidities, were asymptomatic (just 23% for the Abbott test and barely 30% for Roche's), or had previously recovered from COVID.

In addition, the antigen tests also did poorly when PCR analysis indicated that the so-called alpha variant (B.1.1.7) was involved, which the researchers could not explain. They noted that earlier lab studies had found no loss of sensitivity with this variant.

Positive and negative predictive values were generally good when estimated for the entire group of 2,215, at well above 90%, but negative predictive value plummeted for those with no symptoms.

Also, as seen in previous studies, sensitivities for the antigen tests were inversely correlated with the PCR cycle threshold values -- indicating that the rapid tests did better when individuals had relatively high viral loads.

Wertenauer and colleagues suggested that the antigen tests were likely to be even less accurate when nonprofessionals or the individuals themselves collect the samples and run the tests.

The study did have limitations, of course, which the authors acknowledged. PCR testing is not perfect, they noted, and cycle threshold values are only loosely correlated with infectivity and may vary substantially from one lab to another.


Disclosures

The study was funded by Synlab, a provider of laboratory testing services in Germany.

Most of the authors were Synlab employees.

Flexion Publishes Results of Phase 2 Study of ZILRETTA in Shoulder Osteoarthritis

 

  • Data published in Drugs in R&D confirms extended-release PK profile of ZILRETTA (triamcinolone acetonide extended-release injectable suspension) in patients with shoulder OA

  • Plasma PK data indicate the total and maximal exposure to triamcinolone acetonide (TA) was approximately two-thirds lower in patients treated with ZILRETTA compared to triamcinolone acetonide in crystalline suspension (TAcs)

  • Registration trial in patients with shoulder OA expected to begin later this year

COVID vaccines would be required for military under new plan

 Members of the U.S. military would be required to have the COVID-19 vaccine beginning Sept. 15, under a plan announced by the Pentagon Monday and endorsed by President Joe Biden.

That deadline could be pushed up if the vaccine receives final FDA approval or infection rates continue to rise.

“I will seek the president’s approval to make the vaccines mandatory no later than mid-September, or immediately upon” licensure by the Food and Drug Administration “whichever comes first,” Defense Secretary Lloyd Austin says in the memo to troops, warning them to prepare for the requirement.

He added that if infection rates rise and potentially affect military readiness, “I will not hesitate to act sooner or recommend a different course to the President if l feel the need to do so. To defend this Nation, we need a healthy and ready force.”

Austin’s plan provides time for the FDA to give final approval to the Pfizer vaccine, which is expected early next month. Without that formal approval, Austin would need a waiver from Biden to make the shots mandatory. Biden has made it clear he supports that.

In a statement Monday, Biden said he strongly support’s “Austin’s message to the Force today on the Department of Defense’s plan to add the COVID-19 vaccine to the list of required vaccinations for our service members not later than mid-September.”

Biden said the country is still on a wartime footing and “being vaccinated will enable our service members to stay healthy, to better protect their families, and to ensure that our force is ready to operate anywhere in the world.”

Austin’s memo to the force went out Monday.

His decision comes a bit more than a week after Biden told defense officials to develop a plan requiring troops to get shots as part of a broader campaign to increase vaccinations in the federal workforce. It reflects similar decisions by governments and companies around the world, as nations struggle with the highly contagious delta variant that has sent new U.S. cases, hospitalizations and deaths surging to heights not see since the peaks last winter.

Austin said in his memo says that the military services will have the next few weeks to prepare, determine how many vaccines they need, and how this mandate will be implemented. The additional time, however, also is a nod to the bitter political divisiveness over the vaccine and the knowledge that making it mandatory will likely trigger opposition from vaccine opponents across the state and federal governments, Congress and the American population.

Troops often live and work closely together in barracks and on ships, increasing the risks of rapid spreading. And any large outbreak of the virus in the military could affect America’s ability to defend itself in any national security crisis.

The decision will add the COVID-19 vaccine to a list of other inoculations that service members are already required to get. Depending on their location around the world, service members can get as many as 17 different vaccines.

Austin’s memo also said that in the meantime, the Pentagon will comply with Biden’s order for additional restrictions on any federal personnel who have not been vaccinated. Those restrictions will include wearing masks, social distancing and travel limits.

According to the Pentagon, more than 1 million troops are fully vaccinated and another 237,000 have received one shot. But the military services vary widely in their vaccination rates.

The Navy said that more than 74% of all active duty and reserve sailors have been vaccinated with at least one shot. The Air Force, meanwhile, said that more than 65% of its active duty and 60% reserve forces are at least partially vaccinated, and the number for the Army — by far the largest service — appears to be closer to 50%.

Military officials have said the pace of vaccines has been growing across the force, with some units — such as sailors deploying on a warship — seeing nearly 100% of their members get shots. But the totals drop off dramatically, including among the National Guard and Reserve, who are much more difficult to track.

Some unvaccinated service members have suggested they’d get the shot once it’s required, but others are flatly opposed. Military officials have said that once the vaccine is mandated, a refusal could constitute failure to obey an order, and may be punishable under the Uniform Code of Military Justice.

Army guidance, for example, includes counseling soldiers to ensure they understand the purpose of the vaccine and the threat the disease poses. The Army also notes that if a soldier “fails to comply with a lawful order to receive a mandatory vaccine, and does not have an approved exemption, a commander may take appropriate disciplinary action.”

Military service officials have said they don’t collect data on the number of troops who have refused other mandated vaccines, such as anthrax, hepatitis, chicken pox or flu shots over the past decade or more. And they weren’t able to provide details on the punishments any service members received as a result of the refusal.

Officials said they believe the number of troops refusing other mandated vaccines is small. And the discipline could vary.

Also, service members can seek an exemption from any vaccine — either temporary or permanent — for a variety of reasons including health issues or religious beliefs. Regulations involving the other mandatory vaccines say, for example, that anyone who had a severe adverse reaction to the vaccine can be exempt, and those who are pregnant or have other conditions can postpone a shot.

Some have argued that those who have already had the virus — and have antibodies — are immune and thus should not have to get the shot. It’s not clear how the military will act on those types of assertions.

According to defense officials, some senior military leaders have expressed support for making the vaccine mandatory believing it will help keep the force healthy. Military commanders have also struggled to separate vaccinated recruits from unvaccinated recruits during early portions of basic training across the services in order to prevent infections. So, for some, a mandate could make training and housing less complicated.

Navy officials said last week that there has been only one case of COVID-19 hospitalization among sailors and Marines who are fully vaccinated. In comparison, the Navy said there have been more than 123 hospitalizations “in a similarly sized group of unvaccinated sailors and Marines.” It said fewer than 3% of its immunized troops have tested positive for COVID-19.

The other military services did not provide similar data.

https://apnews.com/article/coronavirus-vaccine-us-military-requirement-pentagon-3975940c732352f72e41f6e34a3a2669

German study proves inaccuracy of rapid antigen tests for variants, medium to low viral loads

 . The COVID-19 Antigen Study (COVAG Study), conducted by SYNLAB, the Universities of Heidelberg and Graz, and a large

    COVID-19 test centre in Stuttgart, is one of the most comprehensive systematic evaluations of rapid antigen testing 
    in a real-life setting 
  . The COVAG Study confirms a significantly lower accuracy of rapid antigen tests compared to PCR tests, determining 
    the actual sensitivity of rapid antigen tests at about 60 percent 
  . Study results imply that rapid antigen tests have a lower sensitivity when testing for new virus variants 
  . Effectiveness of rapid antigen tests as a tool to control the pandemic is limited 

SYNLAB, Europe's leading medical diagnostic services provider, collaborated with researchers from the Universities of 
Heidelberg and Graz, and a large COVID-19 test centre in Stuttgart to conduct the COVID-19 Antigen Study (COVAG Study). 
The COVAG Study is one of the most comprehensive field research studies to systemically assess the actual sensitivity 
and specificity of rapid antigen tests. 
The results indicate that the actual sensitivity of two commonly used rapid antigen tests considered reliable, are only 
at 60.4 and 56.8 percent, respectively, compared to PCR tests. In addition, for the first time the COVAG Study 
identified a variant-dependency of rapid antigen tests: the sensitivity of the tests is significantly lower when 
detecting the alpha variant compared to their sensitivity when detecting the SARS-CoV-2 wild-type. 
338 out of 2,215 individuals participating in the study tested positive for SARS-CoV-2 using the PCR testing method. Of 
these 338 positive cases, however, the two rapid antigen tests only identified 204 and 192 participants, respectively, 
as virus carriers. In other words, rapid antigen tests missed four out of ten individuals who tested positive for 
SARS-CoV-2 with PCR tests. Here, the viral load was the most decisive factor for the detection of the virus. Only 
individuals with a very high viral load (CT value <= 20) were reliably detected as virus carriers by rapid antigen 
tests. The virus, however, already spreads at a medium to low viral load. 
In addition, the COVAG Study was the first to investigate variant dependence of rapid antigen tests in samples with 
moderate to high viral loads (CT value <= 30). For the SARS-CoV-2 wild-type, the two rapid antigen tests' sensitivity 
was determined with 87.7 and 84.0 percent, respectively. Yet, for the alpha variant the same tests' sensitivity was 
only at 77.1 and 72.3 percent, respectively. Compared to other circulating variants, however, the alpha variant has the 
lowest structural deviation from the SARS-CoV-2 wild-type. Accordingly, it can be assumed that the sensitivity of rapid 
antigen tests is also significantly lower for other virus variants than for the original wild-type. Meanwhile, however, 
the latter has been completely displaced by the spread of new variants. 
https://www.marketscreener.com/quote/stock/SYNLAB-AG-122186741/news/PRESS-RELEASE-German-COVAG-Study-proves-significant-inaccuracy-of-rapid-antigen-tests-in-detecting-36108642/

Gilead to require U.S. workers receive COVID-19 vaccine

 Gilead Sciences Inc said on Monday it will require all its employees and contractors in the United States to become vaccinated against COVID-19.

The biotech company's move comes less than a week after U.S. drugmaker Pfizer said all its U.S. workers would need to get vaccinated or undergo regular COVID-19 testing.

All Gilead U.S. employees will be required to be fully vaccinated against COVID-19 as of Oct. 1, where allowed by law and where the vaccine supply is readily available, the company said in a statement.

With U.S. coronavirus cases rising sharply again due to the highly transmissible Delta variant, companies like Alphabet Inc , Apple Inc and Walt Disney Inc have started putting vaccine mandates in place for their employees.

For employees with religious beliefs or medical conditions that prevent them from getting vaccinated, Gilead said it will offer an appropriate accommodations review process.

As of Sunday, 50.1% of the U.S. population had been fully vaccinated against COVID-19, according to data from the U.S. Centers for Disease Control and Prevention.

https://www.marketscreener.com/quote/stock/GILEAD-SCIENCES-INC-4876/news/Gilead-to-require-U-S-workers-receive-COVID-19-vaccine-36113735/

BioNTech says vaccine repeats beat devising new one for now

 

BioNTech said that repeat shots of its COVID-19 vaccine, of which more than a billion doses have now been supplied worldwide, was a better strategy than tailoring the product it developed with Pfizer to new variants.

The German biotech firm said that offering a third dose of its established two-shot vaccine remained the best response to concerns over waning immune protection in the face of the highly contagious Delta variant, as worse strains may emerge.

BioNTech said the more than one billion supply tally as per July 21 was up from 700 million-plus doses it announced in June.

This compares with AstraZeneca saying last month that it and manufacturing partner Serum Institute of India had supplied a billion doses of its vaccine globally.

Based on delivery contracts signed for more than 2.2 billion doses so far, BioNTech said in a statement detailing its second quarter earnings that it expects to accrue 15.9 billion euros ($18.7 billion) in revenue from the vaccine this year, up from a May forecast of 12.4 billion euros.

That includes sales, milestone payments and a share of gross profit in its partners' territories, BioNTech added.

Pfizer late last month raised its forecast for its share of 2021 vaccine sales to $33.5 billion and said at the time it believes people will need a third dose of the shot.

Pfizer and BioNTech's decision in early July to seek authorization for a third dose drew criticism from U.S. health regulators, who said there was not yet enough data to show booster shots are needed.

U.S. health agencies have since discussed additional doses for people with compromised immune systems, while Germany and France said they would roll out a third dose for the most vulnerable from September.

That jars with a call by the World Health Organization to use doses instead to jump-start vaccination campaigns in poorer nations which have so far been left behind.

BioNTech Chief Executive Ugur Sahin said that although work was ongoing to adjust the vaccine to variants it was not clear whether yet another version of the pathogen would supplant the now prevalent Delta variant.

"Making a decision at the moment might turn out to be wrong in three or six months if another variant is dominating," Sahin said during an analyst call.

Chief Medical Officer Oezlem Tuereci said lab experiments had shown that a third shot of the established product generated neutralising antibodies against a range of strains and that the antibody boost was above the one following a second dose.

Still, the company reiterated plans to start testing a vaccine adjusted to the Delta variant on humans this month, part of a "comprehensive strategy to address variants".

https://www.marketscreener.com/news/latest/BioNTech-says-vaccine-repeats-beat-devising-new-one-for-now--36110869/