AstraZeneca pauses coronavirus vaccine trial, shares slip on rollout doubts By Reuters


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© Reuters. FILE PHOTO: The company logo for pharmaceutical company AstraZeneca is displayed on a screen on the floor at the NYSE in New York

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By Ludwig Burger

LONDON (Reuters) – AstraZeneca’s (L:) suspension of global trials of its experimental coronavirus vaccine after an unexplained illness in a study subject in Britain has cast doubt on prospects for an early rollout.

The vaccine, which Britain’s AstraZeneca is developing with the University of Oxford, has been described by the World Health Organization as probably the world’s leading candidate and the furthest developed.

AstraZeneca said on Tuesday it had paused trials, including late-stage ones, to allow an independent committee to review safety data, and it was working to minimise any potential impact on the timeline.

“It is obviously a challenge to this particular vaccine trial,” Britain’s Health Secretary Matt Hancock told Sky News.

The patient was suffering from neurological symptoms associated with a rare spinal inflammatory disorder called transverse myelitis, said Chief Executive Pascal Soriot, according to Stat News, citing investors who had listened to a call it said was organised by J.P. Morgan.

The diagnosis has yet to be confirmed, but the patient is recovering and will likely be discharged from the hospital soon, the CEO reportedly added.

The pause follows reports that the United States was aiming for fast-track authorization or approval before November’s presidential election.

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Coronavirus update: Global death toll edges toward 900,000 as AstraZeneca halts vaccine trial after patient struck by illness


The number of confirmed deaths from the coronavirus that causes COVID-19 worldwide edged closer to 900,000 on Wednesday, and the U.S. death toll moved close to 190,000, as AstraZeneca halted trials of its vaccine candidate after one participant was struck by an unexplained illness.

The news sent AstraZeneca shares
AZN,
-1.13%

AZN,
-0.53%

lower, while the stocks of other drug makers developing vaccines, including Pfizer Inc., BioNTech SE and Moderna Inc.
MRNA,
+4.17%

rallied.

In an emailed statement, AstraZeneca said: “As part of the ongoing randomized, controlled global trials of the Oxford coronavirus vaccine, our standard review process was triggered and we voluntarily paused vaccination to allow review of safety data by an independent committee.”

It added that it is working to expedite the review of the single event to minimize any potential impact on the trial timeline. “We are committed to the safety of our participants and the highest standards of conduct in our trials.”

See:Vaccinating children against the flu is ‘more important than ever’ this year: pediatricians

A report in the New York Times said that the volunteer in the U.K. trial received a diagnosis of transverse myelitis, an inflammatory syndrome that affects the spinal cord. “However, the timing of this diagnosis, and whether it was directly linked to AstraZeneca’s vaccine, is still unknown,” the NY Times said. The British drugmaker declined to the comment.

For more, read:AstraZeneca stock falls as drugmaker pauses vaccine trial after volunteer’s ‘unexplained illness’

The news comes a day after AstraZeneca and eight other drug makers working on vaccines made a joint pledge to “stand with science” on coronavirus vaccines, making clear that they would not move forward with such products before demonstrating their safety and efficacy. The unusual pledge comes amid concerns the Trump administration may try to rush out a vaccine before the November presidential election.

Don’t miss: There are seven coronavirus vaccine candidates being tested in the U.S. — here’s where they stand

The World Health Organization reiterated Wednesday that safety has to come first with vaccine development. Dr. Soumya Swaminathan, chief scientist at the WHO, said at a news briefing that regardless of the speed with which drug makers are working, “it doesn’t mean that we start compromising or cutting corners on what would normally be assessed.”

Dr. Anthony Fauci, head of the National Institute for Allergies and Infectious Diseases and a member of the White House Task Force created to manage the pandemic, agreed.

In an interview with CBS, Fauci said it’s routine for a late-stage trial of a vaccine to be put on hold because of side effects, describing it as a safety valve, as the AP reported.

Fauci said a safe and effective coronavirus vaccine may be ready in early 2021.

“The more likely scenario is that we will know by the end of this calendar year and hopefully we’ll be able to start vaccinations in earnest as we begin early 2021,” he said.

In other news:

• French Prime Minister Jean Castex tested negative for the coronavirus in an initial test. Castex was tested after he spent part of the weekend with the head of the Tour de France cycling race, Christian Prudhomme, who tested positive, according to Reuters. France’s cabinet is holding its weekly meeting remotely for the first time since the end of the virus lockdown, AFP reported, and Castex is self-isolating at his official Paris Matignon residence for seven days.

• The British government is banning gatherings of more than six people in England, as officials try to keep a lid on daily new coronavirus infections after a sharp spike across the U.K. that has been largely blamed on party-going young adults disregarding social distancing rules, the AP reported. The law in England will change from next week to reduce the number of people who can gather socially from 30 to six, with some exemptions.

The number of confirmed cases of the virus rose to almost 3,000 on Sunday, before dipping to 2,460 on Tuesday. Failure to comply could result in a 100-pound ($130) fine. The U.K. has the fifth highest death toll from COVID-19 in the world at 41,675, according to data aggregated by Johns Hopkins University. On a per capita basis, it has the fourth highest mortality rate in the world with 61 deaths per 100,000 people, after Peru, Belgium and Spain, according to AFP data.

• Greece’s largest migrant camp on the island of Lesbos was destroyed in a fire that has left more than 13,000 asylum seekers homeless, the BBC reported. The Greek government has declared a four-day state of emergency. It’s unclear how the blaze began with some locals blaming migrants and others blaming locals.

The UNHCR, the UN refugee agency, said it was aware of “tensions” between nearby townsfolk and the migrants. “We urge all to exercise restraint,” it said, and asked anyone who had been at the camp “to restrict their movements and stay near [the site], as a temporary solution is being found to shelter them.”

• Former Italian Prime Minister Silvio Berlusconi, who is in hospital in Milan after testing positive for COVID-19 last week, said doctors treating him have told him he has was “No. 1” for the severity of his viral load, the Guardian reported. Berlusconi, 83, said that of the thousands of coronavirus tests carried out at San Raffaele hospital, doctors told him that he had the worst viral load. “[The virus] is very bad,” he said. “I’m giving it my all, I hope to make it and to get back on track,” he said in a phone call to a candidate from his Forza Italia party, the paper reported.

Read now: How Black doctors are answering the call to reform medical education — and bringing COVID-19 vaccine trials to communities of color

Latest tallies

There are now 27.6 million confirmed cases of COVID-19 worldwide, the Johns Hopkins data shows, and 898,426 people have died. At least 18.6 million people have recovered.

The U.S. has 6.3 million cases and 189,718 deaths. The U.S. added 28,550 new cases on Tuesday and 462 deaths, according to a New York Times tracker. That was down from an average of 36,704 over the past week, which was down 13% from the average two weeks earlier, the paper said. There are concerns those numbers could start to tick up if infections were spread by people gathering in large numbers over the Labor Day weekend, according to the Washington Post.

Brazil has the second-highest death toll at 127,464 and 4.16 million cases. India is third with 73,890 deaths and 4.37 million cases.

Mexico has fourth-highest death toll at 68,484 and 652,860 cases.

China, where the illness was first reported last year, has 90,087 cases and 4,733 deaths, according to its official numbers.

Is there other medical news?

Pfizer Inc.
PFE,
+0.83%

and BioNTech SE
BNTX,
+3.62%

plan to pursue regulatory review for their COVID-19 vaccine candidate BNT162b2 in October, depending on the success of the vaccine in late-stage clinical trials, MarketWatch’s Jaimy Lee reported.

However, the companies did not say what countries they plan to seek review in.

“When the [Phase 3] study reads out will depend on multiple variables but right now, our model, our best case, predicts that we will have an answer by the end of October,” Pfizer CEO Albert Bourla said Tuesday on the Today show, later noting that he means a clinical answer, not a regulatory one.

See also:To defeat COVID-19, ‘we need a unified national strategy,’ says public health expert Dr. Howard Koh

The companies also announced findings from the preclinical study of BNT162b2, which were published as a preprint, showing that when the vaccine was tested in macaques it prevented infection with the virus.

The companies also concluded exploratory talks with the European Commission (EU) for a proposed deal to supply 200 million doses of their vaccine candidate to the EU. The deal would include an option for an additional 100 million doses. T

he deliveries would start by the end of 2020, subject to regulatory authorization. Financial terms under discussion were not disclosed.

“We have activated our supply chain, most importantly our site in Belgium, and are starting to manufacture so that our vaccine would be available as soon as possible, if our clinical trials prove successful and regulatory approval is granted,” said Pfizer Chief Executive Albert Bourla.

What are companies saying?

• Alaska Air Group Inc.
ALK,
-4.18%

expects third-quarter capacity to be down about 55% from the year-earlier period as the pandemic continues to weigh. The airline expects September revenue to be down 70% to 75%, after a 72% decline in August. It expects its passenger load factor to come to 40% to 45%, after 46% in August. It expects available seat miles to be down about 50% after being down 51% in September. The company’s cash burn is expected to total about $150 million in September, after $80 million in August. The carrier had about $3.6 billion in cash as of Sept. 8.

• G-III Apparel Group Ltd.
GIII,
+0.69%

swung to a loss in the second quarter from a profit a year ago and posted sales that fell short of expectations, as the pandemic weighed. Second-quarter losses include a 53-cents-per-share loss due to the liquidation of 110 Wilsons Leather and 89 G.H. Bass stores. Other G-III brands include Donna Karan and Andrew Marc, and licenses for brands like Guess, Cole Haan and Calvin Klein. “We have reset our order book for the balance of the year and shifted our product assortment to athleisure, jeans, casual sportswear and coats,” said G-III Chief Executive Morris Goldfarb in a statement. For the second half of the fiscal year, G-III forecasts a sales decline in the range of 28% to 33%. The company did not provide additional guidance due to uncertainty from the pandemic.

• Hawaiian Airlines parent Hawaiian Holdings Inc.
HA,
-5.65%

provided an update on recent developments, including a modified reinstatement of a 14-day quarantine requirement imposed on passengers traveling from the Island of Oahu to the counties of Maui, Kauai and Hawaii, given an increase in COVID-19 case counts on Oahu. The requirement is effective Aug. 11. Separately, the air carrier expects capacity for the third quarter to be down 87% from the same period a year ago, which is slightly lower than previous forecasts, as a result of reduced travel demand resulting from government actions. Regarding demand, the company said flow passengers for the third quarter through Aug. 31 were down 87% and revenue passenger miles were 96% below last year’s levels. Hawaiian said it received confirmation that its allocation of the Coronavirus Aid, Relief and Economic Security (CARES) Act funds increased to $420 million from $364 million. The company has until Sept. 30 to determine whether it will draw any portion of those funds.

• HD Supply Holdings Inc.
HDS,
+3.56%

reported fiscal second-quarter profit that beat expectations while sales fell in line with forecasts. The industrial distributor company’s facilities maintenance sales fell 8.3% to $761 million, but topped the FactSet consensus of $752.2 million, while construction and industrial sales slipped 0.3% to $793 million to miss expectations of $802.3 million. The company said it was not providing a financial outlook for the third quarter or the full year, given uncertainties over the effects of the COVID-19 pandemic, but said August sales were $518 million, representing an average daily decline of 0.7%.

• LVMH Moet Hennessy
MC,
-0.11%

will not be able to complete the previously announced takeover of U.S. luxury goods retailer Tiffany
TIF,
-10.12%

“as it stands.” LVMH cited both a letter from the French government asking for a delay in light of the threat of tariffs on French products by the U.S., as well as Tiffany’s request to extend the deadline from Nov. 24 to Dec. 31. Tiffany for its part filed a lawsuit in Delaware to enforce the acquisition. “The lawsuit not only makes clear that LVMH is in breach of its obligations relating to obtaining antitrust clearance, but also refutes LVMH’s suggestions that it can avoid completing the acquisition by claiming Tiffany has undergone a Material Adverse Effect (”MAE”) or breached its obligations under the Merger Agreement, or that the transaction is in some way inconsistent with its patriotic duties as a French corporation,” said the Tiffany release.

• MasterCraft Boat Holdings Inc.
MCFT,
-19.98%
,
the recreational powerboat maker, reported a narrower-than-expected fiscal fourth-quarter loss and provided an upbeat sales outlook. Sales for the quarter, which is historically the lowest of the year, dropped 58% to $51.1 million, due primarily to lost production as a result of COVID-19-related shutdowns, but was above the FactSet consensus of $36.8 million. Dealer inventories at the end of the fiscal year were 40% to 50% lower than a year ago. For the first quarter, the company expects sales to be down in the low-to-mid teens percentage range, while the current FactSet consensus of $86.2 million implies a 21.5% decline.

• Rocket Companies Inc.’s
RKT,
+4.63%

Quicken Loans subsidiaries are planning to offer $1.25 billion in senior notes due 2029 and 2031. The mortgage and financial services company, which went public last month, said it expects to use the proceeds from the debt offerings to pay down all of the $1.25 billion of 5.75% senior notes due 2025. Rocket joins the many companies issuing record levels of debt during the pandemic.

• United Airlines Holdings Inc.
UAL,
-4.03%

lowered its outlook for third-quarter capacity and passenger revenue, and but said it has witnessed “a moderate improvement” in travel demand over the past couple of weeks. United now expects third-quarter capacity to be down 70% from a year ago, compared with previous guidance for a 65% decline. Passenger revenue is now expected to be down 85%, versus previous guidance for an 83% decline. “The company does not currently expect the recovery from COVID-19 to follow a linear path. As such, the company’s actual flown capacity may differ materially from its currently scheduled capacity,” United said. The company affirmed its Q3 average daily cash burn rate of $25 million, and said it still expects total available liquidity to be over $18 billion at the end of the quarter.

• United Parcel Service Inc.
UPS,
+2.15%

expects to hire more than 100,000 employees for the holiday season, which is the same as last year despite expectations of record seasonal volume. . The seasonal hires will support expected increase in package volume that is expected to begin in October and continue through January. “We’re preparing for a record peak holiday season. The COVID-19 pandemic has made our services more important than ever,” said Chief Human Resources Officer Charlene Thomas. The package delivery giant said that over the past three years, about 35% of seasonal hires were later hired for permanent positions. About one-third of UPS’s current 123,000 employees started in seasonal positions.



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Coronavirus Vaccine Roundup, Early September


It’s been a while since I went through the whole vaccine landscape (I’ve been putting it off!), but there’s a lot to catch up on. I’m going to incorporate some slightly reworked material from my July post in the introduction to each vaccine class, for reference, but everything on the candidates themselves is updated information. That earlier post includes more background on each specific candidate that I won’t be repeating here.

Viral Vectors

This class uses some other infectious virus, but with its original genetic material removed. In its place goes genetic instructions to make coronavirus proteins, and when your infected cells do that, these proteins will set off an immune response. Note that this is different than being infected with a “real” virus, whose instructions are (naturally enough) to produce more virus, which go off and infect more cells. No, in this case, each viral particle that you’re injected with will be able to infect one cell, and that’s it. An advantage of this approach is that it should appear to your immune system like a pretty realistic viral attack and set off a full range of responses. A disadvantage is that this technique (as far as I can tell) has only once been used in human therapy (the Ebola vaccine), although it’s had a lot of work from a lot of groups over the years. Things have now accelerated – a phrase that you can just keep using these days. Another disadvantage is that if you pick a viral vector that infects people anyway, some of your patients may already have antibodies to that one. That can mean that your attempt to repurpose it might crash and burn as your carefully engineered vector gets attacked by antibodies and eaten by immune cells before it can even do its work. It also means that booster shots would have an uphill battle, since the antibodies from that first dose will be waiting for the second one. Antibodies to the viral payload: good. Antibodies to the viral vector itself: not so much.

Oxford/AstraZeneca (AZN): ChAdOx1-nCov19/AZD122: This one has been in thousands of patients in the UK, Brazil, and South Africa, and the team recently announced a trial in the US as well. And even though I just finished up talking about how booster shots with a viral vector can be tricky, that’s exactly what they’re studying: two doses, four weeks apart. Clinical results released in late July looked promising. There have been a number of supply deals announced, with this being the latest one, and both the EU and the US have paid to reserve hundreds of millions of doses if the clinical results are sufficient for a rollout.

CanSino (CASBF)/AMMS: We had clinical data from this one at about the same time as the Oxford publication. And you could indeed see the preexisting-immunity problem with this adenovirus (the more common human-infecting Ad5, as opposed to the Oxford chimpanzee adenovirus); the paper itself stated that this was a big concern. CanSino has just cancelled plans for a Phase III trial in Canada, for reasons that frankly are still obscure – probably politics, but to be honest, Canada is doing pretty well with the pandemic and is probably not a good place to collect Phase III data to start with. But they’re starting a 5,000-patient trial in Saudi Arabia, and have announced a Phase III in Russia, with plans to go into Pakistan and Mexico as well. Now, those populations have plenty of coronavirus cases, unfortunately. But I remain skeptical that the Ad5 platform is going to come through – existing immunity varies in different populations around the world, but in general, it looks like too many people already have antibodies to the vector itself.

Johnson & Johnson (Janssen) (JNJ): These folks have another obscure adenovirus (Ad26) in an attempt to avoid those problems. They’ve announced a Phase III trial starting this month that looks like the largest in the field (up to 60,000 patients) in locations all around the world. They’ve also been signing deals for reserving hundreds of millions of doses, should things work out, and continue to expand their manufacturing capacity. From what I can see, they’re the only ones at present who are not running a booster-shot trial, which could be an interested logistical advantage for them.

Gamaleya Research Institute: This one is a two-shot dosing program, but one of them is an Ad5 vector and the other is an Ad26. This is the Russian vaccine that made so many headlines not long ago, and for the moment, I have no more to say than I said at the time: its “approval” in Russia was nothing more than a publicity stunt.

Reithera: This one is a gorilla adenovirus, for the same immune-evading reasons as the other unusual vectors above. The company has announced that the first human volunteer was dosed late in August in an Italian Phase I trial, and that it hopes to go into Phase II/III by the end of the year.

Altimmune (ALT): This is another adenovirus vector, but this time administered intranasally (which can be a real logistic advantage over injections). The company also says that it expects the candidate to be storable at room temperature, another real advantage given what we’ve been hearing recently, but we’ll see how that holds up. The company and its partners at Alabama-Birmingham have announced what look like solid results in mouse models, but it’s obviously behind the more highly publicized vaccine candidates when it comes to human dosing.

Merck (MRK)/Themis: This is the first non-adenovirus vector candidate on this list – it uses the measles virus, actually. The company has said that it plans to start human trials in this quarter, which means this month, but we have very little data otherwise. Merck’s Roger Perlmutter has said, though, that with this one and the IAVI candidate (next paragraph), they’re trying for a one-dose vaccine rather than a booster shot regimen.

Merck/IAVI: The vector in this case is VSV, the virus used in the Ebola vaccine (which, as mentioned above, is the only one so far in humans that uses this viral vector delivery idea). This one is said to be going into humans by the end of the year. The hope is that this one could be orally administered in a “swish-and-swallow” manner, which would certainly be an advantage.

Vaxart (VXRT): This company has also announced work on an oral coronavirus vaccine candidate, but information has been very hard to come by since then. I cannot find any data, nor any idea of when a trial might start. What I do find is lots of fans of the stock – not necessarily the company’s fault, because coronavirus therapy stocks have, of course, been an insane circus all year long, but it does make the signal/noise rather poor. We’ll see if some solid information appears eventually.

Washington University: A recent paper in Cell describes this chimpanzee adenovirus candidate. Interestingly, while an immune response was certainly induced in mice when the vaccine was given by injection, but an even more robust protective effect was seen when it was given intranasally. You have to wonder if the eventual coronavirus vaccine that people will take routinely will be a nasal one, but it’s for sure that whatever rolls out in the next few months will not be.

MediciNova (MNOV): This Japanese company has an influenza virus vector platform that it’s also using to try to develop an intranasal coronavirus vaccine. It has announced some mouse model data; we’ll see if this one can make a place for itself in human trials.

Genetic Vaccines

These take DNA or RNA coding for coronavirus proteins and inject that directly into the bloodstream (all of the ones below are mRNA, except for Inovio (INO), Genexine (GNXCF), Zydus Cadila (CDLYY), and AnGes (AMGXF)). “Directly” isn’t quite the right word, though – for these things to work, they have to be formulated and modified to survive destruction in the blood, to be taken up through cell membranes, and to be used for protein production once they’re inside. There have been extensive experiments in animal models over the years, but this is another category where no existing human vaccine uses the technology (yet!) Advantages include fast development and (possibly) ease of manufacture, depending on how exotic the final form turns out to be, and lack of an existing immune response to the vaccine itself (as seen with some of the viral vectors above). The big disadvantage is, well, once again, no one has taken these things into humans yet. Another one is that it looks like the ones under development will need to be stored under rather stringent cold-chain conditions.

Moderna (MRNA): Well, you can’t open up a news site without reading something about Moderna. So, I’ll highlight that the company has released some data on its vaccine candidate’s performance in older patients (looks good). The company says that it is on target to complete enrollment in its Phase III trial by the end of this month, and (in response to some worries) is now publishing data on the diversity of its patient population. Like all the front-runners, we are waiting on efficacy data, and everything we have to say now will be outweighed by what those numbers tell us.

Pfizer (PFE)/BioNTech (BNTX): This one is also on track to complete enrollment late this month, and the company continues to stick with its optimistic timelines. Pfizer CEO said today that they might have results in October, but that means the very end of October, surely.

Inovio: I have been searching, but I have no new science results to talk about with this DNA vaccine candidate. It’s a stock market fight, and another short-selling firm just came out with a very pessimistic report. And sure, that’s what short-sellers do, but they’re not always wrong, either. I have never been optimistic about these folks, and I have seen no reason to change my opinion. Hammer me for it, fanboys.

CureVac (CVAC): The company has a Phase I trial underway in Germany and Belgium, and it’ll be interesting to compare its data to Moderna and Pfizer/BioNTech when it completes. The company is already negotiating with the EU about supplying its candidate if it works, and says that its timeline would put that in the middle of next year.

Imperial College: I believe that this is the leading self-amplifying mRNA candidate left, after Pfizer and BioNTech dropped theirs. It has shown good results in mice, and a Phase I trial is underway in England, with reports of trials starting in Uganda by the end of the year. An advantage of the self-amplifying platform is (as you’d figure) that it takes lower dosages, but it’s not something that (to my knowledge) has been tried in humans until now.

Arcturus (ARCT)/Duke-NUS: Here’s the other self-amplifying candidate that I’m aware of, which went into humans just a couple of weeks ago in Singapore. Arcturus has both an mRNA platform and a lipid-based delivery platform, which have come together under the current conditions to get into the clinic very quickly indeed.

Sanofi (SNY)/Translate Bio (TBIO): Some slides have emerged in a regulatory filing that show immune responses in animal models. No idea when this one is going into humans, although it’s supposed to be soon.

Zydus Cadila: This DNA candidate has been through phase I, and early in August, received approval to go into Phase II trials. To the best of my knowledge, though, we have no data other than the company’s statement that it was well-tolerated in Phase I. The CEO has said that they hope to launch the vaccine itself next March.

Genexine: This DNA vaccine candidate has now been into primate models, and is approved to start clinical trials in Korea – but I can’t find a firm date when that’s supposed to happen.

AMMS/Abogen/Walvax: This one (China’s lone mRNA candidate, from what I can see) has been approved for human trials, but other than that, details are very hard to come by. I don’t even know if it’s been dosed yet or what the timeline is.

AnGes/Osaka/Takara Bio (TKBIF): This is a Japanese collaboration on another DNA vaccine candidate, which has begun recruiting for human trials. This one combines a DNA plasmid with a skin-penetrating jet injection device, so it’ll be a more complicated development to get through.

Recombinant Protein Vaccines

Here, we get to a technique that really is used for human vaccines. The previous two categories force your own cells to make viral antigen proteins, but here, you’re making those proteins industrially and just injecting them directly. The advantage can be that such protein production can be accomplished in many different ways and is already done on a large scale. That said, every new protein is a new project, with its own idiosyncrasies. A disadvantage is that this technique sometimes does not produce enough of a robust immune response by itself (at reasonable doses of protein, anyway), and needs added “adjuvants” as part of the vaccine formulation. These are substances that increase immunologic reaction – through mechanisms that honestly have not always been so well-understood over the years (more here), and you’ll see these in the entries below.

Novavax (NVAX): This company seems to be the leader in this area at the moment. It has just published results from its Phase I/II trials, and the antibody responses look good after the second dose of the company’s adjuvant-containing vaccine. The results were, in fact, quite similar in the 5-microgram and 25-microgram dosage groups, which highlights the work that the adjuvant is doing. CD4+ T cells were also induced (Th1 phenotype, as in the other vaccines that have reported so far), but there were no data on CD8+. It looks like this one will be handled under standard refrigerator temperature shipping and storage. The safety profile looks good so far as well. So, like the others in human trials, we’re going to have to wait for the key efficacy numbers to sort things out – in an interesting development, though, Novavax is the only vaccine developer (so far) to explicitly say that it would be willing to take the FDA up on Commissioner Hahn’s recent proposal to have companies file for approval before their Phase III trials are complete.

Sanofi/GlaxoSmithKline (GSK): Coming up fast now is this Big Pharma competitor. The companies have announced today that they’ve started a Phase I/II trial at 11 sites across the US, with a Phase III to start in December. This one is using GSK’s adjuvant technology, which is already in human vaccines, and will also be shipped and stored at refrigerator temperatures (and not freezers or worse, like the mRNA candidates).

Clover Biopharmaceuticals: This company has already been in human trials for a while now, but there’s absolutely nothing new to report, from what I have seen. Not sure what’s going on here, and I hope to see some results soon.

Queensland/CFL/GSK: This one has been in human trials since back in July (no word yet). A preclinical animal study has been done in hamsters, though. It’s worth noting that this one uses a so-called “molecular clamp” technique to try to keep the viral protein in a more antigenic conformation, which is different from the other candidates in this area.

Zydus Cadila: This Indian company is also in human trials.

Vaxine: This Australian company has partnered with Oxford Expression Technologies to try out recombinant Spike protein with Vaxine’s proprietary adjuvant. Phase II trials are supposed to begin this month.

Medigen: This is a Taiwan-based company with yet another mixture of Spike proteins and adjuvant from Dynavax (DVAX). A human trial is set to begin this month.

Adimmune: Another Taiwan effort with a Spike protein, and this one has already begun human dosing there.

UBI: Still another Taiwan protein vaccine, but this one (from what I can see) is a mixture of several antigens. It has just received permission from Taiwan’s regulatory authorities to start human dosing.

Zhifei Biological Products: As far as I can see, there’s been nothing substantial about this one since the announcement of Phase II trials back in early July.

Stabilitech: No updates on this one, either, that I have been able to find.

Attenuated Virus Vaccines

This is another well-precedented vaccination technique. It involves producing a weakened form of the actual infectious virus – one that is not capable of causing damage but can still set off the immune system. There are several ways to do this, and it’s a bit of an art form involving taking the virus through a huge number of replications in living cells as you select for variants that are less and less harmful. An advantage is that such vaccines can be quite effective at raising a response – ideally, the immune system reacts exactly as it would to the real pathogen, except you avoid all the getting sick part. A disadvantage is that part about it being an art form: balancing the lack of harm with immunogenicity is not something that can always be achieved. Some viruses have a wider window for this sort of thing than others, and it’s not easy (or possible, really) to know if this is a feasible pathway upfront. That may well be one reason why (at the moment) I know of only one company pursuing this route.

Meissa Vaccines: This small company announced back earlier in the summer that it had had a pre-IND meeting with the FDA about its attenuated coronavirus program and was doing preclinical studies. If there has been more news since then, I have not been able to track it down.

Inactivated Virus Vaccines

This is also a technique that’s been used in medical practice for many years, and it’s another inactivation step beyond the attenuated viruses. Heat or chemical agents are used to damage the virus to the point that it can no longer infect cells at all, but the plan is for there to be enough of the viral material left unaltered to still raise an immune response. Not the most high-tech approach, but it can definitely work. Many times, though, vaccines of this kind don’t provide enough of a response in a single shot, so you will very likely looking at a booster vaccine schedule. Interestingly, the Chinese groups seem to have this field to themselves; I’m not aware of any inactivated-virus vaccine for the pandemic that’s in serious development anywhere else.

SinoPharm (SHTDF)/Wuhan Institute of Biological Products: This candidate was the subject of a recent publication on a Phase I human trial, and that (while a bit light on details) was notable for a rather mild side-effect profile. We’ll wait on efficacy data. This one is current being tested in the UAE.

SinoPharm/Beijing Institute: This one has sometimes been hard to distinguish from the other SinoPharm candidate, and I have been unable to locate any new information on it.

Sinovac Biotech (SVA): No new scientific data on this one, from what I can find. It’s in Phase III trials in Brazil and Indonesia, but that hasn’t stopped the Chinese government from authorizing its use in high-risk groups of government employees. Both governments have signed agreements to purchase the vaccine if it continues to show good clinical data.

Institute of Medical Biology (China): Nothing new on this one since it was said to be entering clinical trials in June.

Bharat Biotech: This candidate is currently in Phase I/II trials at several locations in India, and the company has also received permission to conduct a separate trial with intradermal dosing (which should, in theory, use less vaccine per dose). What we’re not seeing is any more of the craziness back in July that would have had the vaccine theoretically launched two weeks ago, which is a relief.

Virus-Like Particles

Here’s yet another category, which can be thought of as a “stripped virus”. A VLP has most or all of the surface proteins of the real virus, but doesn’t have the genetic payload inside, and therefore, cannot replicate. But the immune response that develops to the surface antigens is still available. This technique is already used for vaccines against HPV and Hepatitis B, so it’s proven that it can work well. You have several options for preparing such VLPs, mixing and matching material from the natural virus (or more than one natural virus) and recombinant proteins.

Mitsubishi-Tanabe/Medicago: This is a plant-based candidate, coming from tobacco leaves (see the July post linked in the first paragraph today for more). Some plant-derived proteins can have very different immunogenic profiles than the “same” protein produced by other methods (different glycosylation patterns, generally). They’re currently in Phase I, with plans (I typed “plants” the first time) to go on to Phase II/III in October. They’re using adjuvants from both GSK and from Dynavax to go along with their proteins.

Kentucky BioProcessing: This is another tobacco-leaf protein production company, from R.J. Reynolds. I’m not sure whether to put it here in the VLPs or up in the recombinant protein section, but I’ll leave it here next to Medicago for convenience. The company has completed preclinical testing on its candidate and is awaiting FDA approval to go into human trials.

Oxford/SpyBioTech: Here’s a new one, based on a protein engineering system known as “Spytag/Spycatcher“. Molecular biology aficionados will know this one already – it’s an efficient protein conjugation method, with these two domains engineered to form a new covalent bond to each other when you express them in your desired targets and let them mix. That’s been used to put Spike antigen proteins (the RBD part) onto a known VLP called mi3, a technique that was already being investigated before the coronavirus epidemic even showed up. Mice given the RBD itself raised a detectable but not very strong immune response, but when the RBD was conjugated to the mi3 particles, that construct set off a much more potent and wide-ranging antibody response. I don’t know if this can get into human trials in time to help, but it looks quite interesting.

Wrap-up

Dang, that’s a lot of vaccine candidates. And as you can see, it’s a long-tail distribution – there are some big ones that everyone knows about, but a lot of people are bringing a lot of technologies to bear on the problem. This makes me think that we’re going to have a multichapter story, in the end. There will be the first vaccines approved, then the second wave, then the improvements on those, until we have (with luck, hard work, skill, and lots of money) tossed this virus out of the human population and back to the bats, pangolins, or whoever had it in the first place.

An excellent side effect is that vaccine technology will never be the same after this – it’s going to be like aircraft design before and after World War II, and for many of the same reasons. This whole pandemic has been awful, in many different ways, but we’re going to come out of it stronger and more capable than when we went in.

Disclosure: None.

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Editor’s Note: The summary bullets for this article were chosen by Seeking Alpha editors.





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Sweden adopted a controversial approach to tackling the coronavirus. Here’s how it plans to save Christmas


Sweden’s strategy to tackle the pandemic is singular: avoid lockdowns to keep the economy going and encourage herd immunity from the virus.


Pontus Lundahl/Agence France-Presse/Getty Images

If Anders Tegnell is right, with a bit of holiday magic Swedes may be able to swap strict social distancing for a slightly more normal Christmas with family and friends this year.

Sweden’s state epidemiologist told SVT, the state broadcaster, that the country may soon be ready to ease the isolation of the elderly in time for the winter holiday season as the country hopes the coronavirus pandemic is under control.

If Sweden loosens its public health recommendations for the elderly, who are at high risk for the coronavirus, it would signal another distinctive move from a country with a controversial approach to the pandemic.

As coronavirus cases continue to climb in the United States by tens of thousands per day, and public debate rages over what, if any, restrictions should be imposed, all eyes are on how Sweden fares. Can this snowy Nordic country save Christmas for its citizens?

Read this: Sweden didn’t impose a lockdown, but its economy is just as bad as its neighbors

The strict social distancing recommendations for people over 70 are currently being investigated, Tegnell said, but as long as the trend remains positive in Sweden, families and friends should be able to get together at Christmas as long as they think it through properly and keep some distance.

The epidemiologist said that the existing recommendations would remain in place for the elderly and very ill in nursing homes. 

Also: Sweden embraced herd immunity, while the U.K. abandoned the idea — so why do they both have high COVID-19 fatality rates?

Sweden’s strategy to tackle the pandemic is singular: avoid lockdowns to keep the economy going and encourage herd immunity from the virus. Herd immunity is achieved when enough of the population has been infected by the virus that collective immunity prevents further spread. 

Tegnell has also rejected the need for people to wear face masks to prevent the spread of the virus, against the advice of the World Health Organization.

Watch: School returns in Wuhan

Nearly 1.4 million students returned to class in Wuhan, China, this week. WSJ’s Jonathan Cheng explains how schools reopened in the city where the coronavirus first emerged and what’s at stake for Beijing if they have to close again. Photo: Aly Song/Reuters

The coronavirus infection rate in Sweden dropped below 1,000 cases per day in late June and has remained at about 150 cases per day this week.

Sweden’s approach is controversial because many people have already died and it remains to be seen how effective striving for herd immunity is in the long-run.

Read more: Sweden is developing herd immunity, some of the country’s experts claim, but the figures say otherwise

As it stands, 5,832 people have died from the virus in Sweden, which has a population of over 10.2 million people. This compares with its Scandinavian neighbours, Denmark and Norway, which both have a population of about half of Sweden’s and a combined 890 deaths between them.

Sweden has a coronavirus death rate of 57.15 per 100,000, which is the tenth highest in the world, according to Johns Hopkins University. Denmark and Norway have a death rate of 10.80 and 4.97 per 100,000, respectively.



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Asymptomatic children who contract COVID-19 may ‘shed’ coronavirus for weeks


Should families double down on social distancing now that their kids are going back to school?

A new study published in JAMA Pediatrics suggests that children can spread SARS-CoV-2, the virus that causes COVID-19, even if they never develop symptoms or even long after symptoms have cleared. It found a significant variation in how long children continued to “shed” the virus through their respiratory tract and, therefore, could potentially remain infectious. 

While the virus was detectable for an average of about 2.5 weeks in the entire group, a significant portion of the children —about a fifth of the asymptomatic patients and about half of the symptomatic ones — were still shedding virus at three weeks, meaning they were releasing it into the environment. The researchers also found that the duration of COVID-19 symptoms also varied widely, from three days to nearly three weeks. 

A recent systematic review estimated that 16% of children with a SARS-CoV-2 infection are asymptomatic, but evidence suggests that as many as 45% of pediatric infections are asymptomatic, according to the U. S. Centers for Disease Control and Prevention. The signs and symptoms of COVID-19 in children are similar to other infections and noninfectious processes, including influenza, according to the CDC

Such research comes at an important time for communities. Under pressure from the teachers union to delay the start of the school year.

While children infected with SARS-CoV-2 are less likely than adults to develop severe illness or complications, they are still at risk of becoming ill. “Recent COVID-19 hospitalization surveillance data shows that the rate of hospitalization among children is low (8 per 100,000 population) compared with that in adults (164.5 per 100,000 population),” the CDC said.

Such research comes at an important time for families and communities. Under pressure from the teachers union to delay the start of the school year, New York City Mayor Bill de Blasio announced Tuesday that in-person classes will be pushed back until Sept. 21, 11 days later than planned. Remote learning, also originally slated to start on Sept. 10, will now commence on Sept. 16.

Other countries have not fared so well with school reopenings. Israel, which also reopened schools this week, had less success when it reopened schools on May 17 amid high temperatures that made it difficult for students to wear masks, full classrooms that made social distancing near-impossible and, perhaps, the illusion that the virus had been vanquished, creating a false sense of security.

The risk, as Israel discovered, is providing an environment where children unwittingly spread the virus to each other, which can lead to community transmission. That’s particularly worrying for those who have underlying conditions, and the elderly, who are more vulnerable to the most severe effects of the virus. Community transmission also makes contact tracing more difficult.

A school outbreak can lead to community spread, hence the need for staggered school reopenings, social distancing and reduced class sizes. “If we find a certain number of symptomatic people testing positive, we expect the same number of asymptomatic carriers that are much more difficult to identify and isolate,” said Enrico Lavezzo, a professor in the University of Padua’s department of molecular medicine, who coauthored a study released in June of a quarantined town in Italy.

Children may shed virus for weeks

The latest study in the peer-reviewed JAMA Pediatrics focused on 91 pediatric patients at 22 hospitals in South Korea. “Unlike in the American health system, those who test positive for COVID-19 in South Korea stay at the hospital until they clear their infections even if they aren’t symptomatic,” said Roberta DeBiasi, chief of the Division of Infectious Disease at the Children’s Hospital in Washington, D.C.

The patients were identified for testing through contact tracing or after developing symptoms. About 22% never developed symptoms, 20% were initially asymptomatic but developed symptoms later, and 58% were symptomatic at their initial test. The hospital staff tested them every three days on average, providing a picture of how long viral shedding continues over many weeks.

Among the important findings from the study: Children, a group widely thought to develop mostly mild disease that quickly passes, can shed virus for weeks, DeBiasi and Meghan Delaney, chief of the Division of Pathology and Lab Medicine at the Children’s National Hospital in Washington, D.C., wrote in a commentary piece to accompany the study in JAMA Pediatrics. 

There were a large number of asymptomatic children: About one-fifth of the group of children studied across 22 South Korean hospitals.

Other key points: Even asymptomatic children continued to shed coronavirus after testing positive, making them potential key vectors. In this study at least, there were a large number of asymptomatic patients: About one-fifth of the group in South Korean hospitals. Researchers said the study provides important insight on the role children might play in the spread of COVID-19.

But the study also had obvious limitations. One of these relates to the link between testing and transmission. A “positive” or “negative” result may not necessarily mean that a child is infectious, “with some positives reflecting bits of genetic material that may not be able to make someone sick,” or, on the other hand, “negatives reflecting low levels of virus that may still be infectious.”

Researchers may have tested different parts of the respiratory tract and different testers may yield different results. It’s unclear whether symptomatic children shed different quantities of virus than symptomatic patients. They tested for the active virus — not antibodies — excluding those who may have had and cleared an asymptomatic or mild infection, an important factor for understanding herd immunity.

However, DeBiasi said studies such as these can add to the knowledge of public-health efforts being developed and refined to bring COVID-19 under control. “Each of these pieces of information that we, our collaborators and other scientists around the world are working to gather is critical for developing policies that will slow the rate of viral transmission in our community,” she said.

Coronavirus update

As of Thursday, COVID-19 had infected 26,118,288 people worldwide, which mostly does not account for asymptomatic cases, and killed 864,801. The U.S. still has the world’s highest number of COVID-19 cases (6,131,344), followed by Brazil (3,997,865), India (3,853,406) and Russia (1,006,923), according to data aggregated by Johns Hopkins University.

Cases keep rising in the U.S. with California becoming the first state in the country to surpass 700,000 confirmed cases; infections hit 721,281 there as of Thursday with 13,317 COVID-related deaths. New York has recorded 436,218 infections and the highest number of deaths in the U.S. (32,972). COVID has killed 186,293 people in the U.S.

AstraZeneca AZN, -1.10% , in combination with Oxford University; BioNTech SE BNTX, -5.61% and partner Pfizer PFE, -2.40% ; GlaxoSmithKline GSK, -1.61% ; Johnson & Johnson JNJ, -1.23% ; Merck & Co. MERK, -0.31% ; Moderna MRNA, -2.41% ; and Sanofi SAN, -1.34% are among those currently working toward COVID-19 vaccines.

The Dow Jones Industrial Index DJIA, +0.75%, the S&P 500 SPX, +0.75% and the Nasdaq Composite COMP, +1.39% were trading lower Thursday. Doubts about traction for further fiscal stimulus from Washington may be one factor discouraging investors who have been betting on Republicans and Democrats striking a deal to offer additional relief to consumers and businesses.



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