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Wednesday, January 27, 2021

Those Covid-19 variants? ‘Don’t worry yet,’

On Tuesday, Paul Offit, the vaccine developer and a professor of pediatrics at Children’s Hospital of Philadelphia, dropped by, virtually, for a conversation with STAT+ subscribers. During the discussion, he addressed a question on everyone’s mind: How worried should we be about new variants of SARS-CoV-2, the virus that causes Covid-19?

Offit — who, overall, believes “we’re going to turn the corner,” with the help of vaccines — had plenty of worries. A rare side effect of the vaccines could emerge and scare people away from them, even when the benefits far outweigh its risks. It could take a long time to fix vaccine distribution and manufacturing problems.

But he said his biggest concern is that a new variant of the SARS-CoV-2 virus will learn to evade the vaccines. He also explained, at length, why he doesn’t think it’s time for you to worry yet. The transcript of that explanation follows; it has been edited for clarity and length.

Offit: So this is a bat coronavirus — it’s not a human coronavirus — that made its debut in the human population in November 2019. It will adapt to growth in humans, and when it adapts, it will create variants. It created a variant the minute it left Wuhan, the so-called 614 variant, which was somewhat more contagious. Since then, it’s created at least four variants that we know of — the U.K. variant, the South African variant, the Brazilian variant and then, just in the last few days, the California variant.

So the critical question is not are variants being produced. Of course they’re going to be produced. The critical question is do these variants make the virus more contagious, more virulent, and most importantly, far and away most importantly, have these variants evaded recognition by vaccine-induced immune response? That’s the critical question.

Here’s what I would say. It looks like the U.K. variant is somewhat more contagious. The good news is it’s still spread by small droplets, so masking and physical distancing still work. I don’t think there’s good evidence that the U.K. variant is more virulent. If you look at people who are hospitalized in the U.K., you are no more likely to die if you’re hospitalized with a variant strain or not. That may change over time.

The critical question is, have these viruses mutated away from the vaccine? The way you’re going to know that, the proof for that, is when you see people who have gotten two doses of vaccine who are then hospitalized and who are shown to be infected with a variant strain. That’s the proof. Everything else that we’re looking at is just a way to predict whether or not that happens. And the predictions are not perfect.

So, for example, if you look at the U.K. variant, both Pfizer and Moderna have taken serum from people who were immunized with their vaccines and shown that those sera neutralize the U.K. variant in the same manner that they neutralize the non-variant viruses. So therefore one should be reassured.

But if you look at the South African variant, it looks like when the companies take the sera from people who were immunized with their vaccines and see whether you can neutralize that South African variant in the laboratory, it shows that there’s a decreased capacity of those antibodies that are obtained from people who are immunized to neutralize that virus. Now, it’s unclear what that means. Just because you have a lesser capacity to neutralize that virus doesn’t mean that you’re not still protected. Because we don’t really know the level of neutralizing antibodies that’s associated with protection. Even though it’s a lesser response, that doesn’t mean it’s still not an adequate response.

The second thing is you’re just looking at one aspect of the immune system, which is neutralizing antibodies. There are other aspects of your immune system that are associated with protection. One is called T-helper cells, which are a kind of T cells that actually help your B cells make antibodies. And those are much more broadly cross-reactive. The second thing is so-called cytotoxic T cells, which are T cells that kill virus-infected cells. All three of those parts of the immune system are important for protection or at least amelioration of disease. And we’re only looking at neutralizing antibodies when we’re doing these studies.

So I would say, don’t worry yet. We don’t really have any evidence that people who have been given two doses of these vaccines are at greater risk. We’ll see what happens with the South African strain. Interestingly, studies of unapproved vaccines are being done now in South Africa. So we’ll see whether or not people who get those vaccines in South Africa are relatively protected against this strain. We’ll know this over time. But I would say don’t worry yet.

https://www.statnews.com/2021/01/27/those-covid-19-variants-dont-worry-yet-vaccine-expert-says/

EU eyes tighter COVID-19 vaccine exports as access gets ugly

 The EU has hit back at AstraZeneca’s plan to provide fewer doses of its COVID-19 vaccine than expected, saying it wants to see exactly where supplies have been delivered so far.

Moreover, it plans to rush through legislation requiring that all companies producing vaccines against COVID-19 in the EU have to notify the Commission when they want to export to third countries, according to Commissioner Stella Kyriakides, who is in charge of the EU vaccine rollout.

That would include the Pfizer/BioNTech vaccine – which is made in Belgium – and has sparked concerns that supplies of that vaccine destined for the UK could be held back as a retaliatory move.

In a statement, Kyriakides said AZ’s responses to enquiries “have not been satisfactory so far”, and another meeting of EU27 member states has been scheduled for Wednesday to discuss the matter further.

On Friday, AZ told the Commission it was falling behind on its supply targets because of production delays, following in the footsteps of Pfizer/BioNTech, which has also had to reduce supplies due to capacity constraints at the Belgian plant.

To recap, the AZ vaccine – developed in conjunction with Oxford University – hasn’t yet been approved in the EU, although the Commission says that should occur “by the end of this week”.

The EU has ordered 300 million doses and has an option on 100 million more, but a Reuters report says first-quarter deliveries to the EU could be 60% lower than expected at around 31 million.

The combative stance taken by the EU has led some to suggest it is diverting attention from criticism of a much slower-than-expected rollout of vaccines, a process which is being managed centrally by the Commission, by some member states including Germany.

Other countries, including Australia and Thailand, have also been informed of a reduction in supply of the AZ shot, according to the BBC, which suggests that problems at a plant in Belgium run by one of AZ’s manufacturing partners is at the root of the issue, although other reports point to spoiled batches and problems sourcing some raw materials.

A spokesperson for AZ said: “While there is no scheduled delay to the start of shipments of our vaccine should we receive approval in Europe, initial volumes will be lower than originally anticipated due to reduced yields at a manufacturing site within our European supply chain. We will be supplying tens of millions of doses in February and March to the EU, as we continue to ramp up production volumes.”

The EU’s target is to vaccinate 70% of the adult population of EU countries by the summer, which looks unlikely if supply issues persist. The UK government has said it is confident the supply of vaccines will not be disrupted by the EU’s export plans.

Meanwhile, AZ has also been forced to defend its vaccine after an unsourced report in German financial newspaper Handelsblatt claimed that it only has efficacy of 8% in people aged over 65.

The company says that is “completely incorrect. In the UK, the JCVI [Joint Committee on Vaccination and Immunisation] supported use in this population and MHRA included this group without dose adjustment in the authorisation for emergency supply.”

It goes on: “In November, we published data in The Lancet demonstrating that older adults showed strong immune responses to the vaccine, with 100% of older adults generating spike-specific antibodies after the second dose.”

Moderna takes on new strains

Moderna meanwhile has said that its vaccine seems to be effective against the emerging UK and South African variants of SARS-CoV-2, but appears less effective against the latter when it comes to stimulating the production of antibodies.

The company it is starting a trial of a new vaccine against the B1351 variant, which is more transmissible and may also be associated with higher mortality, saying it wants to make sure that a shot will be available in the next few months as a precautionary measure.

The current shot produces antibodies that are six-fold lower against the SA variant than the original form of SARS-CoV-2, but are still at levels expected to be protective, said the US biotech.

https://pharmaphorum.com/news/eu-eyes-tighter-covid-19-vaccine-exports-as-access-gets-ugly/

2nd prophylaxis win for Covid-19 antibodies

 Like Lilly, Regeneron reckons its antibodies can be used to prevent Covid-19 infection. Now comes the hard part.


Regeneron has matched Lilly in showing that it has a viable approach to preventing Covid-19 infection with an antibody. Both companies’ MAbs carry US emergency use authorisation as Covid-19 treatments, and clinical data suggest that they could soon become available in the prophylactic setting too.

The focus will now turn to logistics. Unless such antibodies are made significantly more convenient and quicker to administer at home the positive results might not count for much, and the respective treatments risk going down as little more than scientific curiosities.

The data Regeneron released today relate to an interim analysis of Study 2069, testing casirivimab plus imdevimab versus placebo in households where one or more individuals is infected with Covid-19. This is subtly different from Lilly’s reported passive immunisation data on bamlanivimab in Blaze-2, a trial in nursing homes.

Bamlanivimab is given via a 60-minute IV infusion, while the Regeneron combo was given as a subcutaneous injection said to be “more convenient and efficient for patients and overburdened healthcare providers and facilities”. Just how convenient this kind of drug must be to allow widespread outpatient use is the big question.

Impressive results

The data, however, are impressive. Regeneron says the first 409 subjects randomised into Study 2069 showed a 50% reduction in confirmed Covid-19 infections, the trial’s co-primary endpoint. Specifically, there were 23 infections among the 223 placebo recipients versus just 10 in the 186 given Regeneron’s combo of casirivimab plus imdevimab.

The company offered no statistical analyses, but noted that the trial has enrolled over 2,000 patients, and according to clinicaltrials.gov it has a recruitment target of 2,450. However, even if the numbers are still too small to yield statistical significance, the numerical benefit is clear.

Further analyses, most strikingly concerning symptomatic infections, paint an even more positive picture. None of the actively treated patients developed symptomatic Covid-19, Regeneron said, while eight of the 23 infections in placebo recipients were symptomatic.

Moreover, in the treated group the infections showed a shorter average duration of viral shedding (nine versus 44 weeks), and infected placebo recipients showed peak viral loads more than 100-fold higher than those infected in the active cohort.

There was also a reduction in infection duration – three to four weeks for placebo, versus a week or less for casirivimab plus imdevimab. Again there were no statistics provided, and some will criticise Regeneron for cherrypicking data, but merely reducing Covid-19 severity is still seen as a real benefit.

For its part Lilly last week said bamlanivimab cut risk of developing symptomatic Covid-19 by 57% versus placebo among nursing home residents and staff, and by 80% among residents (Lilly Blazes a trail in Covid-19 prevention, January 21, 2021). Unlike Regeneron the company provided no absolute infection numbers, but did cite odds ratios and p values, which were highly positive.

Selected prevention studies with Covid-19 antibodies
ProjectDosingCompanyTrialSettingData?
Bamlanivimab (LY-CoV555)*IVLilly/AbcelleraBlaze-2Prevention in nursing home residents and staffOdds ratio for infection 0.43 (p=0.00021) for treatment vs placebo in all 965 initially Covid-19 -ve subjects; 0.20 (p=0.00026) among 299 -ve residents
Casirivimab + imdevimab (REGN-COV2)SCRegeneronStudy 2069Prevention in household contacts of Covid-19 patients10/186 treated subjects infected (0 symptomatic) vs 23/223 infections (8 symptomatic) for placebo
AZD7442IMAstrazenecaProvent"Pre-exposure prophylaxis"Due H1 2021
IMStorm Chaser"Post-exposure prophylaxis"
*Trial also includes combo with LY-CoV016 in treatment. Source: clinicaltrials.gov & EvaluatePharma.

Lilly and Regeneron both say they want to discuss the prevention data with regulators with a view to broadening their MAbs’ EUAs.

If Regeneron’s combo has a convenience advantage over Lilly’s MAb then it shares this with a third competitor, Astrazeneca. The UK group has not yet reported prevention data with AZD7442, a MAb dosed intramuscularly.

The stage is now set for dosing convenience and logistics to be an increasingly important consideration as companies try to get these types of passively immunising antibodies into domestic settings at scale. The risk is that there will be no contest against the more typical vaccination already being rolled out globally.

https://www.evaluate.com/vantage/articles/news/trial-results/second-prophylaxis-win-covid-19-antibodies

J&J tight-lipped ahead of next week's Covid-19 vaccine data

 Pivotal data on Johnson & Johnson’s one-shot Covid-19 vaccine candidate failed to materialise alongside the company’s annual results today, but the world does not have long to wait, with the readout promised for early next week. In the meantime, executives gave away little, other than to express optimism based on encouraging early data. Questions on durability, the need for a booster and efficacy against new variants were also rebuffed, with J&J's chief executive, Alex Gorsky, saying it would be “inappropriate to speculate” on the outcome given the proximity of hard data. Poor efficacy would be a huge disappointment, particularly given Merck & Co’s exit from the vaccine queue yesterday, and considering the huge quantities of product that J&J would be able to supply. On this subject, execs said they were “very comfortable” that firm purchase commitments could be met this year – a nod to news that Astrazeneca has joined Pfizer/Biontech in facing supply problems in Europe. J&J also reiterated its pledge that the shot would not cost more than $10, adding that the final price would depend on demand, which in turn depends on the data. The final countdown begins.

J&J's pivotal trials of vaccine candidate Ad26.COV2-S
TrialDetailsReadout 
Ensemble Testing single-dose regimen; target recruitment 60,000w/c Feb 1, 2021 
Ensemble 2 Testing two-dose schedule, target recruitment 30,000 Q4 2021
Source: company statements. 

https://www.evaluate.com/vantage/articles/news/snippets/jj-tight-lipped-ahead-next-weeks-covid-19-vaccine-data

Anthem Expects Covid-19 Pandemic to Hurt 2021 Earnings

 Anthem Inc. said it expects the Covid-19 pandemic, including the one-year increase in Medicare physician rates brought on by the passage of the Consolidated Appropriations Act, to hurt its 2021 earnings by 50 cents a share to 70 cents a share.

The health insurer on Wednesday said it expects full-year earnings of more than $23.51 a share, including about 99 cents a share in net unfavorable items. Excluding those items, the company sees adjusted earnings of more than $24.50 a share. Anthem reported 2020 earnings of $17.98 a share, or $22.48 a share on an adjusted basis.

The company said it expects operating revenue to rise almost 12% in 2021 over the prior year to $135.1 billion, and for premium revenue to rise to between $114.5 billion and $115.5 billion.

Anthem said it sees a medical-loss ratio, or the share of premiums the insurer pays out in claims, of 88%, compared with 84.6% in 2020.

By the end of 2021, it expects medical enrollment of 44.1 million to 44.7 million, compared with 42.93 million in 2020.

https://www.marketscreener.com/quote/stock/ANTHEM-INC-18740543/news/Anthem-Expects-Covid-19-Pandemic-to-Hurt-2021-Earnings-32286588/

Glaxo to move malaria vaccine production to India's Bharat Biotech

 

Britain's GSK will shift production of the world's first effective malaria vaccine to Indian COVID-19 vaccine developer Bharat Biotech, as part of global efforts to battle the deadly fever, the drugmakers said on Wednesday.

The agreement includes transfer of manufacturing of the protein part of the vaccine, RTS,S/AS01, while GSK will continue to supply Bharat Biotech with the adjuvant or vaccine booster for the shot, the joint statement said.

The vaccine, developed by GSK for over three decades and with nonprofit group PATH since 2001, is currently being administered under a special World Health Organization-backed scheme in Ghana, Kenya, and Malawi.

Malaria is caused in humans by five types of parasites transmitted through the bite of a certain variety of infected female mosquitoes.

Two of these parasite variants, including Plasmodium falciparum, against which the GSK vaccine was developed, pose the greatest threat.

"Helping secure the long-term future of the only vaccine available by working with an established leader like Bharat Biotech is vital for the continued fight against this devastating disease," said Thomas Breuer, the chief medical officer for vaccines at GSK.

There were 229 million cases of the disease worldwide in 2019, with 94% of the malaria cases and deaths occurring in Africa, according to the WHO.

London-listed GSK has committed to donate up to 10 million doses of the vaccine to WHO's pilot program, and supply up to 15 million doses annually until 2028 if recommended for wider use by the U.N. agency.

Hyderabad, India-based Bharat Biotech has been supplying vaccines to the Indian region, vaccine alliance GAVI and UNICEF, and currently manufactures 17 licensed vaccines including those for typhoid and polio.

It is expected that Bharat Biotech will be the sole supplier of the malaria vaccine by 2029 at the latest, with GSK continuing to supply the adjuvant to them, the companies said.

https://www.marketscreener.com/quote/stock/GLAXOSMITHKLINE-PLC-9590199/news/GSK-to-move-malaria-vaccine-production-to-India-s-Bharat-Biotech-32287091/

Abbott Laboratories Sees Larger-Than-Expected 2021 Profit

 Abbott Laboratories on Wednesday projected that its full-year adjusted profit will be higher than analysts had previously forecast, as demand for Covid-19 testing continues to drive strong sales.

The Abbott Park, Ill.-based health-products company said it expects full-year earnings of at least $3.74 a share in 2021. Excluding one-time items such as acquisition and amortization expenses, the company's adjusted profit will be at least $5 a share, the company projected.

Analysts surveyed by FactSet had been forecasting a full-year adjusted profit of $4.24 a share.

The company's role in Covid-19 diagnostic testing has been a boon to its revenue, contributing $2.4 billion in sales in the fourth quarter.

https://www.marketscreener.com/quote/stock/ABBOTT-LABORATORIES-11506/news/Abbott-Laboratories-Sees-Larger-Than-Expected-2021-Profit-32287902/