Does AstraZeneca’s trial pause affect other COVID-19 vaccines? Analysts weigh in

In the wake of news yesterday that AstraZeneca had paused its phase 3 COVID-19 vaccine trial due to a serious safety issue, analysts across the biopharma landscape set out to answer questions and lay out possible scenarios about how the race could play out from here. 

Amid its effort to enroll tens of thousands of participants, AstraZeneca voluntarily paused the trial after a patient’s adverse event, Stat reported Tuesday afternoon. The New York Times reports a trial participant in the U.K. was diagnosed with transverse myelitis, inflammation of the spinal cord that can be triggered by infections.  

The development could result in four possible scenarios, SVB Leerink’s Andrew Berens wrote to clients early Wednesday. If the event is determined to not be transverse myelitis or not linked to the AstraZeneca vaccine, the program could proceed after a delay of weeks to months, he wrote. 

But if transverse myelitis is confirmed as a reaction to the vaccine, the program would be “terminated,” Berens wrote. And under two other scenarios linking transverse myelitis to the SARS-CoV-2 virus or COVID-19 infection, other vaccine players would naturally be affected. 

Still, under any scenario, “the overall pace of many of the programs could be impacted as the investigation progresses and the sponsors become more vigilant,” the analyst wrote. 

But in an indication AstraZeneca may have the issue under control, the Financial Times reported on Wednesday the trial could resume next week, citing people familiar with the matter. 

Meanwhile, SVB Leerink’s Mani Foroohar, who on Tuesday downgraded AZ rival Moderna due to competitive pressures, said the mRNA biotech’s share price should react favorably to the news. His team sees “limited readacross” between vaccine platforms from the pause. 

Moderna could now be in a position to arrive second to market behind Pfizer, he wrote. Still, Foroohar stood by his underperform rating for the biotech thanks to fierce competition in the overall COVID-19 vaccine field. 

For now, the issue is part of a “short- to medium-term debate,” Jefferies analyst Michael Yee wrote to clients on Tuesday.  

“We generally believe and have said before that the vaccines, including [Moderna’s], will likely have various differences in efficacy and safety/tolerability and these may drive various opinions about which are best for people,” he wrote. 

SVB Leerink analyst Geoffrey Porges said the issue isn’t cause for panic, but his team is watching it seriously. A rare safety red flag in a large efficacy trial was one of many reasons his team never counted on COVID-19 vaccines for herd immunity until 2023, he wrote. It could take months for to AstraZeneca to prove the problem wasn’t associated with vaccination. Another serious issue could derail the program altogether, Porges wrote. 

As a result of the development, other vaccine makers using adenovirus platforms, such as Johnson & Johnson and CanSino, could face slight delays as they tweak their consent forms and patient brochures, Porges wrote.  

And for developers using other vaccine platforms, there’s “very little direct spillover,” he noted. But the analyst does expect “more careful scrutiny” for vaccines using novel platforms, such as the mRNA programs from Pfizer and Moderna. Companies using traditional technologies such as GlaxoSmithKline, Sanofi and Novavax are in the best position, he added.

All things considered, Porges’ team expects a “politically influenced” emergency use authorization for high-risk populations by the end of the year. Pfizer and Moderna are pressing ahead with mRNA vaccines in late-stage testing, but that technology has never yielded an approved product.  

For a wider approval and widespread use, Porges’ team is expecting to wait until mid- to late 2021. 

https://www.fiercepharma.com/vaccines/how-does-astrazeneca-s-trial-pause-affect-other-covid-19-vaccines-analysts-weigh

AstraZeneca production partner Emergent unlikely to suffer if vax trial hold sticks

AstraZeneca was humming right along with its partnered COVID-19 vaccine with the University of Oxford before a sudden trial hold threw its plans into disarray. So what does that uncertainty mean for AstraZeneca’s expectant manufacturing partners on the shot? For at least one, it could be no issue at all. 

Despite a major commitment from AstraZeneca to help produce bulk drug substance for the University of Oxford’s adenovirus-based COVID-19 shot, Maryland’s Emergent BioSolutions isn’t likely to feel a financial pinch if the British drugmaker’s candidate doesn’t make it across the finish line, Cantor analysts wrote in a note to investors Wednesday. 

On the heels of AstraZeneca’s troubling phase 3 trial hold, Emergent’s share price dropped 5% in early Wednesday trading to $100.22 as investors appeared to show concern that AstraZeneca’s setback would hit the CDMO’s bottom line. 

But according to Cantor, Emergent wouldn’t likely come out worse for wear if AstraZeneca’s candidate flops, as the partners’ contract includes protections for Emergent that will see it rake in most of the $174 million owed to it in year one of the deal. 

Part of that deal, signed in July, is an $87 million portion for tech transfer and preparation that is underway, Cantor said. That money has already come Emergent’s way, and further contract protections will see Emergent made whole on most of the rest, analysts argued.

In fact, investors appeared to agree on that rosy outlook almost immediately, with Emergent’s share price rebounding over the course of the day Wednesday to $106.36 at 12:30 p.m. ET. 

The only unknowns in the event of AstraZeneca’s failure would be the second and third years of the proposed contract, which could be waived, according to Cantor. However, given Emergent’s close relationship with the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), another vaccine maker could easily step into AstraZeneca’s place to continue driving revenues for Emergent. 

Moreover, that alternate partner could secure an even longer-term CDMO contract with Emergent at its Baltimore Bayview facility, largely taking the manufacturer’s risk off the table. 

Despite the uncertainty of AstraZeneca’s fate in the COVID-19 vaccine hunt, Emergent can rest easy knowing it has at least one other major player in the field on its side. 

In early July, Johnson & Johnson and Emergent inked a five-year work order worth at least $480 million to help produce the New Jersey-based drugmaker’s COVID-19 vaccine candidate.

Emergent will provide “large-scale” drug substance manufacturing for J&J’s recombinant DNA shot beginning in 2021, starting with a $480 million order for the first two years of the deal. For the final three years, the partners will use a “flexible capacity deployment model” to provide annual batches as needed, Emergent said.

https://www.fiercepharma.com/manufacturing/astrazeneca-s-vaccine-production-partner-not-likely-to-suffer-if-drugmaker-s-trial

Intra-cellular gets bipolar reprieve

Intra-celluar’s lumateperone is finally to be submitted to the FDA for approval in bipolar disorder after the company reported positive pivotal data with the higher dose when used as an adjunct treatment. Shares rocketed 60% in early trading this morning. The result could reassure investors after mixed data previously; one trial of lumateperone monotherapy was positive while the other failed, which the company blamed on a high placebo response. Efficacy-wise the positive adjunct and monotherapy data appear to be on a par with results seen with the older atypical antipsychotics Latuda and Abilify, with the usual caveats over comparing data from different trials. But lumateperone looks to have the edge in terms of safety: rates of extrapyramidal symptoms and changes in weight were similar between drug and placebo. Intra-cellular plans to file the project in the adjunct and monotherapy settings for both type I and II disease by the end of the year. Should the FDA only approve the adjunct use, another monotherapy study, called 403, is ongoing and could serve as a back-up if positive. Bipolar is a valuable indication, accounting for half of lumateperone’s $2bn sales forecast for 2026, according to EvaluatePharma consensus. The other half come from schizophrenia, where the product was approved as Caplyta last year.

Data from Intra-cellular’s phase III trials in bipolar disorder (placebo-adjusted change from baseline in MADRS total score)
	Study 402 (global)	Study 404 (global)	Study 401 (US only)	Study 403 (global)
	Adjunct	Monotherapy	Monotherapy	Monotherapy
Lumateperone 42mg	2.4 points (p=0.0206)	4.6 points (p<0.001)	1.0 point (not stat sig)	Primary completion June 2021
Lumateperone 28mg	Not stat sig	N/A	-0.8 points (not stat sig)	N/A
Sources: company releases, clinicaltrials.gov.

https://www.evaluate.com/vantage/articles/news/snippets/intra-cellular-gets-bipolar-reprieve

U.S. set to end enhanced screening of some travelers for COVID-19

The U.S. government is set to end enhanced screening of some international passengers for COVID-19 and drop requirements that travelers coming from the targeted countries arrive at 15 designated U.S. airports, according to U.S. and airline officials and a government document seen by Reuters.

The changes are set to take effect as early as Monday, according to the draft rollout plan seen by Reuters, but the move could still be delayed, U.S. officials said.

The administration in February imposed enhanced screening requirements on travelers who had been in China, the United Kingdom, Brazil, Iran and the Schengen region of Europe, and barred most non-U.S. citizens who have been in those locations from coming to the United States.

The document seen by Reuters says the Centers for Disease Control and Prevention (CDC) “is shifting its strategy and prioritizing other public health measures to reduce the risk of travel-related disease transmission.” It said that of 675,000 passengers screened at the 15 airports, “fewer than 15 have been identified as having COID-19.”

The “current entry strategy for international arrivals only covers a small portion of the traveling public, requires significant resources and is not sustainable as travel volumes increase,” document said.

Those travelers, who numbered around 6,750 a day as of late August, undergo visual observations, temperature checks and complete traveler declarations. Anyone showing signs of illness or possible exposure is referred for public health assessments.

Airlines for America, a group representing American Airlines (AAL.O), Delta Air Lines (DAL.N) and United Airlines (UAL.O), said the group supports “spending scarce screening resources where they can best be utilized and no longer believe that it makes sense to continue screening at these 15 airports given the extremely low number of passengers identified by the CDC as potentially having a health issue.”

The plan to halt the checks was reported earlier by Yahoo News.

Last month, Reuters reported that the Trump administration’s efforts to require airlines to collect contact tracing information from U.S.-bound international passengers had stalled, citing five people briefed on the matter, and that such a mandate is unlikely this year.

Major airlines and administration officials held talks for months over a long-standing effort by the CDC to mandate the collection and reporting of tracing information from passengers arriving in the United States from foreign destinations.

The administration also considered requiring temperature checks for all U.S. air travelers and facial coverings at U.S. airports, but opted not to adopt either mandate.

https://www.reuters.com/article/us-health-coronavirus-usa-travelers/u-s-set-to-end-enhanced-screening-of-some-international-travelers-for-covid-19-sources-idUSKBN260343

Some scientists spot ‘unlikely’ patterns in Russia vaccine data: letter

Twenty-six scientists, most of them working at universities in Italy, have signed an open letter questioning the reliability of the data presented in the early-stage trial results of the Russian COVID-19 vaccine, named “Sputnik-V”.

Addressing the editor of The Lancet, the international peer-reviewed medical journal in which Moscow’s Gamaleya Institute published its early-stage trial results, the scientists said they saw patterns in the data that looked “highly unlikely”.

The letter, published on the personal blog page of one of the signatories, said the Phase I/II trial results data showed multiple participants reporting identical antibody levels.

“On the ground of simple probabilistic evaluations the fact of observing so many data points preserved among different experiments is highly unlikely,” the open letter said.

However, the scientists said they were basing their conclusions on summaries of the Russian trial result data, published in the journal, rather than the original data itself.

“In lack of the original numerical data, no conclusions can be definitively drawn on the reliability of the data presented, especially regarding the apparent duplications detected,” the letter said.

The Gamaleya Institute, which developed the vaccine, rejected the critique.

“The published results are authentic and accurate and were examined by five reviewers at The Lancet,” Denis Logunov, a deputy director at the institute, said in a statement.

He said his institute submitted the entire body of raw data on the trial results to The Lancet.

“We presented specifically the data that was produced (by the trial), not the data that is supposed to please Italian experts,” Logunov said.

Naor Bar-Zeev, deputy director at John Hopkins Bloomberg School of Public Health, who peer reviewed the Russian data, defended his analysis of the research.

“Science must maintain a balance between incredulity, skepticism and trust. That trust is borne out through plausibility, repeatability and falsifiability.”

“The results are plausible, and not very different to those seen with other AdV vectored products,” he said.

The researchers had provided more detail than was needed for the review and responded to his questions “intelligently and in a matter-of-fact and confident but understated manner”.

“Bottom line, I saw no reason to doubt the legitimacy of these results over others I have read and reviewed. But of course one can never know,” he said in an email.

A spokeswoman for the Lancet said the journal had invited the study’s authors to respond to the questions raised in the open letter. It was following the situation closely, she said.

Russia published results on Friday of its Phase I/II trial, which included 76 participants and was conducted in June-July this year. Participants developed a positive immune response and no serious side effects, the study’s authors said.

A Phase III trial, involving 40,000 participants, was launched on Aug. 26. Around 31,000 people have already subscribed to take part, Health Minister Mikhail Murashko said.

https://www.reuters.com/article/us-health-coronavirus-russia-vaccine-let/some-scientists-spot-unlikely-patterns-in-russia-vaccine-data-letter-idUSKBN2602Q5

Brazil lab DASA to do tests for COVID-19 vaccine being developed by COVAXX

Brazilian lab and hospital group DASA S.A. said on Wednesday it has agreed to conduct clinical Phase 2 and 3 trials in Brazil for a COVID-19 vaccine developed by COVAXX, a unit of U.S. privately-owned United Biomedical Inc.

COVAXX co-founder Peter Diamandis said in a remote press conference the UB-612 multitope peptide-based vaccine is currently undergoing Phase 1 tests in Taiwan.

Brazil has the third worst coronavirus outbreak after the United States and India, and has become a testing ground for COVID-19 vaccines under development in Britain, China and Russia.

DASA medical director Gustavo Campana said a protocol for the large scale efficacy and immune response tests will be submitted to Brazil’s health regulator ANVISA in December after the Taiwan results are available.

Using a proprietary methodology, the COVAXX vaccine aims to trigger a longer lasting immunity by stimulating the body to produce antibodies. Because it is totally synthetic, using no viruses, the vaccine has a low biological risk, Campana said.

Diamandis said with the partnership, DASA would secure the first 10 million doses of the potential vaccine for the private market in Brazil and COVAXX will make available an additional 50 million doses for the Brazilian public health market.

COVAXX Chief Executive Mei Mei Hu said the company is already producing millions and millions of doses of the vaccine.

COVAXX estimates it can produce 100 million doses in the first four months of next year and 500 million in total in 2021, DASA said in a statement.

DASA said it donated 15 million reais ($2.8 million) towards development of the vaccine with three other partners, Brazilian homebuilder MRV Engenharia SA, Brazil’s largest car rental company Localiza SA and Banco Inter that will together donate another 15 million reais.

https://www.marketscreener.com/quote/stock/MRV-ENGENHARIA-E-PARTICIP-6499822/news/Brazil-lab-DASA-to-do-tests-for-COVID-19-vaccine-being-developed-by-COVAXX-31261263/

CDC reports decline in e-cigarette use among U.S. high schoolers

The percentage of e-cigarette users among high school students in the United States has declined to about 20% in 2020 from 27.5% last year, researchers from the U.S. Centers for Disease Control and Prevention said on Wednesday.

According to a survey of U.S. middle school and high school students during Jan. 16–March 16, 3.6 million youth still used the devices and more than eight in 10 reportedly used flavored e-cigarettes, the agency said in its Morbidity and Mortality Weekly Report (MMWR).

The surge in the use of electronic cigarettes among children and teens prompted U.S. health regulators to crack down on the sale of the products by companies like Juul Labs Inc.

Earlier this year, the Trump administration issued a ban on some popular e-cigarette flavors, including fruit and mint, in cartridge-based e-cigarettes which are often sold in convenience stores, affecting companies like Njoy and Vuse maker R.J. Reynolds Tobacco Co that offer a wide variety of flavors.

Consistent with 2019, prefilled pods or cartridges were the most commonly used device type in 2020, the report noted, adding that the use of disposable e-cigarettes surged among both high school and middle school students.

They most commonly used fruit-flavored e-cigarettes in 2020, with other popular choices being candy, desserts, mint and menthol, the agency said.

About 56% of high school students who used any type of flavored e-cigarettes used mint flavor, according to the report.

The findings also suggest prominent menthol e-cigarette use, including among nearly one-half of flavored prefilled pod or cartridge users and one quarter of flavored disposable product users, the agency said.

https://www.marketscreener.com/news/latest/CDC-reports-decline-in-e-cigarette-use-among-U-S-high-schoolers–31261258/