AstraZeneca PLC (AZN)

[Lootman]

Still, AZN and Oxford are a set of duckeggs especially when they knew mid year that there was a trial problem.

They were given instructions on how to set out the trials and they seem to have deviated and not followed them....double duckeggs!

Having found that the incorrect vaccination regime was not being followed, they very sensibly decided to continue with that regime to obtain their conclusions. If you look at the RNS it is obvious that there are many trials in progress. What we do not know except by speculation in the press is how the initial lower dose came about. That is immaterial if it is found to give a superior result. The important thing is that a properly conducted trial was carried out to its conclusion and gave the results quoted.

It is still a problem though, and not just with perception:

1) The wrong dose was administered, which creates a concern about competence.

2) There needs to be at least a partial do-over of the trials, which will cause a delay in approval, at least in the important US market.

3) The two other vaccines that are this advanced, from Pfizer and Moderna, have higher rates of effectiveness no matter which of AZN's numbers you take. Whilst AZN's 90% effectiveness number was based on a trial group with nobody over age 55.

4) AZN cannot explain why a lower dose is more effective when common sense indicates the opposite would be the case. If a half dose is better than a full dose, then maybe a quarter dose is better again? It all feels a bit random.

5) AZN's one advantage is that it is cheaper, but does cost matter that much here? Moderna's vaccine costs ten times as much, at about 30 quid a pop, but who wouldn't pay that to get a jab that is both more effective and will be available sooner? Heck, I would pay 300 quid if I could get it tomorrow. And AZN basically giving it away for free is noble, but won't make them any money.

[scrumpyjack]

A few comments

I think I read somewhere that the incorrect dose was due to a manufacturing error so they thought they were giving the intended dose but doses had been manufactured incorrectly. It is being manufactured at something like 20 locations round the world by various companies. Nevertheless it obviously reduces AZN's credibility and does raise doubts about quality control.

The inventor of the vaccine (Sarah Gilbert) has been quoted as suggesting a number of perfectly plausible reasons why the lower initial dose appeared to be more effective. They are investigating further.

Their news management has been very bad. It would have been better to be perfectly open in the announcement and set out all the facts clearly rather than having journalists dig it up bit by bit and put their own spin on it.

Nevertheless 70% is well above the 50% effectiveness sought, and this vaccine seems to be the only hope for many many countries. Orders for it are many times the level of order for the other vaccines.

[Lootman]

Nevertheless 70% is well above the 50% effectiveness sought, and this vaccine seems to be the only hope for many many countries. Orders for it are many times the level of order for the other vaccines.

70% is certainly "good enough" in general for a vaccine. But if given the choice I think most people would choose a vaccine that is 95% effective over it. Better for society as a whole as well.

AZN's product will prove popular in the developing world, partly because of the low price point and partly because of the easier supply chain as it doesn't need to be super-frozen, which may be impossible in some poorer countries. But even so, where is the profit there given that AZN is providing this at cost? AZN may garner some goodwill but can I take that to the bank?

[scrumpyjack]

Depends what you mean by 'cost'. there are direct costs but overheads, depreciation, other expenses written off etc etc. So I suspect it will help the bottom line but won't be presented that way. There is a lot of scope for presenting results in the way the directors want, and drug companies have been stretching that to limit in the past with the concept of 'Core' profits and obscuring all the inconvenient costs that come up every year.

Their pledge is to sell it at cost 'to developing countries' and not to turn a profit on it during the pandemic. But the 'costs' may well cover all the costs of building up a large vaccines business, which will continue to generate value after the pandemic is over.

[Bouleversee]

Wasn't the reason the half plus full dose was more successful that it didn't overstimulate the immune system?

I really can't see where 70% average is at all meaningful. The double dose was only 62% successful; the half plus one was 90% but only tried on under 55s. I should imagine it will take some time to conclude the trial of the latter and even if it works to the same degree on a broader spectrum of ages, I doubt if it will get approved in time for the first roll-out. Who would want to settle for 62% if they could get 95%?

I find the thought of a manufacturing error even more frightening than a treatment error. I'd like to know where that batch was manufactured.

[seekingbalance]

The reason 70% or even 62% is “good enough” is for the same reasons all action around virus transmission are centred around reducing incidence. This is not about one person, it is about society.

If even 25% of the population is “immune” it slows transmission, because 1 in 4 people in society can’t “get it”. If 70% can’t catch it then the chances of transmission from a single infected person goes way down, which has a severe knock on effect in reducing transmission.

A good example in reverse is Measles. For decades the world had almost no transmission of measles because almost every child was vaccinated against it. Then came Andrew Wakefield, and now in some areas of the western world less than 50% of kids are vaccinated against it, so we have had some major outbreaks - measles is massively more transmissible than Coronavirus with an unchecked r rate of as high as 18, compared to Covid’s 3. The U.K. as a whole is at about 85% child coverage at age 5 for measles with kids having the second MMR jab. Yet we do not have massive outbreaks across the country, despite this and the high r number, because while 85% is not good for a disease with such high transmission, it is not bad, and creates such a reduced susceptible population it is relatively easy to isolate breakouts.

With a much lower unchecked transmission rate, Covid incidence would dramatically fall if 70% of the population was immune, simply because there are so fewer people in your vicinity that will have it at any one time.

That massively reduces the strain on the healthcare system - which to be clear is essentially the whole reason behind all these Covid measures - and allows countries to get back to firefighting outbreaks with track and trace.

Of course 95% is better, but once you only go down that road you will get a substantial portion of the original naysayers (not quite anti-vax, at least in their own minds, but that is kind of what they are) starting to say “ooh, 95% is not enough, I want a 97%, or a 99% effective vaccine”. This is not true - they don’t want the vaccine at all, but equally they don’t want to be seen as anti-science, and anti-society so they pretend they are “just sayin’”. Therein lies the death of humanity - we need people to stop letting perfect be the enemy of good.

Do we just not bother with seatbelts? They save a lot of lives, but people in car crashes still die while wearing them. Not 100% effective, so why should I wear one, right? Do we stop going out, ever, because there is a change of getting run over, abducted, murdered, mugged? Yes, some very few of us do, but in the main we don’t, yet it is not 100% safe. Do people with cancer refuse any treatment because they are only 20, 30, 50, 80% effective? No - people with cancer fight tooth and nail for treatment that is only 5% effective!

[Bouleversee]

Well, I do want a vaccine jab a.s.a.p. and will getting one p.d.q. and am glad it wiĺl be one which is 95% successful and has apparently been tested on the elderly and highly vulnerable. However, I am sure AZN will soon catch up and their product will be more suited to many locations.

[ADrunkenMarcus]

A good example in reverse is Measles. For decades the world had almost no transmission of measles because almost every child was vaccinated against it. Then came A**** W******* [redacted], and now in some areas of the western world less than 50% of kids are vaccinated against it, so we have had some major outbreaks

I regard that man's name as a swear word! The enormous damage he did, as you rightly point out... Sadly, there's a growth industry of moronic pseudo-science.

Best wishes

Mark.

[ADrunkenMarcus]

AZN's product will prove popular in the developing world, partly because of the low price point and partly because of the easier supply chain as it doesn't need to be super-frozen, which may be impossible in some poorer countries. But even so, where is the profit there given that AZN is providing this at cost? AZN may garner some goodwill but can I take that to the bank?

I'll need to check, but my memory is AZN is only supplying at cost until July 2021 - or had only committed to that, in any case. If COVID-19 does not 'go away' then regular vaccines will presumably be needed which means a recurring revenue stream for pharmaceutical companies.

Best wishes

Mark

[idpickering]

Astra Vaccine Is Effective But Leaves Questions in Older Ages

A vaccine developed by the University of Oxford and AstraZeneca Plc provided protection against severe Covid-19 in a peer-reviewed study, though more analysis will be needed to see how well it works in older people, among those at highest risk in the pandemic.

The 10 cases of hospitalization seen in the trial all occurred among those given a placebo, suggesting the shot prevents the worst symptoms, according to the results published Tuesday in The Lancet medical journal. Yet the vaccine’s efficacy couldn’t be assessed in older age groups because there weren’t enough infections, the data show.

Because older adults were recruited to the studies later than younger ones, “they’ve had less time for cases to accrue in those age groups and for us to be able to measure an efficacy signal,” said Andrew Pollard, director of the Oxford Vaccine Group. “The evidence we have so far on the immune response very much suggests that it’s likely to be similar levels of protection across the ages.”

https://www.bloomberg.com/news/articles ... older-ages

Further to the above, this from AstraZeneca;

Interim analysis showed vaccine is effective at preventing COVID-19, with no severe cases and no hospitalisations more than 21 days after first injection

https://www.astrazeneca.com/content/ast ... ancet.html

[monabri]

https://www.telegraph.co.uk/business/20 ... m-alexion/

"AstraZeneca is buying rare diseases specialist Alexion Pharmaceuticals in a cash-and-shares deal worth $39bn (£31.5bn), the FTSE 100 giant announced on Saturday.

Alexion shareholders will receive $60 in cash and 2.12 AstraZeneca shares, valuing the target at $175 a share." Alexion shares ended at $121 in New York on Friday and started the year at just under $108.

[Dod101]

Not an insignificant purchase. Announcing it on a Saturday? Amazing.

Dod

[idpickering]

Trixeo Aerosphere approved in the EU for COPD

AstraZenecaÕs Trixeo Aerosphere (formoterol fumarate/glycopyrronium bromide/budesonide) has been approved in the European Union (EU) for maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid (ICS) and a long-acting beta2-agonist (LABA), or a combination of a LABA and a long-acting muscarinic antagonist (LAMA).

The approval by the European Commission was based on positive results from the ETHOS Phase III trial in which Trixeo Aerosphere, a triple-combination therapy, showed a statistically significant reduction in the rate of moderate or severe exacerbations compared with dual-combination therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (budesonide/formoterol fumarate) over 52 weeks.1 The approval was also supported by efficacy and safety data from the KRONOS Phase III trial.2

https://www.investegate.co.uk/astrazene ... 00095161I/

[idpickering]

AstraZeneca to acquire Alexion Pharmaceuticals Inc

AstraZeneca and Alexion Pharmaceuticals, Inc. (Alexion) have entered into a definitive agreement for AstraZeneca to acquire Alexion.

Alexion shareholders will receive $60 in cash and 2.1243 AstraZeneca American Depositary Shares (ADSs) (each ADS representing one-half of one (1/2) ordinary share of AstraZeneca, as evidenced by American Depositary Receipts (ADRs)) for each Alexion share. Based on AstraZeneca's reference average ADR price of $54.14, this implies total consideration to Alexion shareholders of $39bn or $175 per share.

The boards of directors of both companies have unanimously approved the acquisition. Subject to receipt of regulatory clearances and approval by shareholders of both companies, the acquisition is expected to close in Q3 2021, and upon completion, Alexion shareholders will own c.15% of the combined company.

Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "Alexion has established itself as a leader in complement biology, bringing life-changing benefits to patients with rare diseases. This acquisition allows us to enhance our presence in immunology. We look forward to welcoming our new colleagues at Alexion so that we can together build on our combined expertise in immunology and precision medicines to drive innovation that delivers life-changing medicines for more patients."

https://www.investegate.co.uk/astrazene ... 00064619I/

[idpickering]

Whether or not the sp movement of AZN this morning, it's down 6.0% as I type, is because of the above announcement, that move seems excessive imho. Either way, such short term movements won't cause me to sell my AZN shares. Having said that, I'm in no rush to top up my holdings either.

Ian.

[Bouleversee]

Whether or not the sp movement of AZN this morning, it's down 5.6% as I type, is because of this announcement, that move seems excessive imho. Either way, such short term movements won't cause me to sell my AZN shares.

Ian.

It could be because according to an article in TT today headed "Astra 'needs to sweeten Alexion bid'" this deal is one of the largest ever takeovers by a UK company and the largest takeover of a US company this year and as your linked announcement stated, it is subject to shareholder approval which the article suggests may not be forthcoming; analysts at SVB Leerink suggest that Astra may have to increase the offer to $200 p.s. to stisfy Alexion shareholders. There may also be counter bids so not in the bag yet. It says the deal carries a $1bn. break fee. It also mentioned speculation that Soriot might be thinking of leaving, "though the right deal might persuade him to stay".

Quite a lot to make us shareholders jumpy.

[idpickering]

Whether or not the sp movement of AZN this morning, it's down 5.6% as I type, is because of this announcement, that move seems excessive imho. Either way, such short term movements won't cause me to sell my AZN shares.

Ian.

It could be because according to an article in TT today headed "Astra 'needs to sweeten Alexion bid'" this deal is one of the largest ever takeovers by a UK company and the largest takeover of a US company this year and as your linked announcement stated, it is subject to shareholder approval which the article suggests may not be forthcoming; analysts at SVB Leerink suggest that Astra may have to increase the offer to $200 p.s. to stisfy Alexion shareholders. There may also be counter bids so not in the bag yet. It says the deal carries a $1bn. break fee. It also mentioned speculation that Soriot might be thinking of leaving, "though the right deal might persuade him to stay".

Quite a lot to make us shareholders jumpy.

Thanks for that Lorna. I get what you’re saying, but I’m staying put with my AZN shares, and thinking longer term than just today.

Ian.

[Bouleversee]

Glad to hear it, Ian. So am I.

[idpickering]

Imfinzi new dose receives positive EU CHMP opinion

AstraZeneca's Imfinzi (durvalumab) has been recommended for marketing authorisation in the European Union (EU) for an additional dosing option, 1,500mg fixed dose every four weeks, in the approved indication of locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on at least 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy (CRT).

This new dosing option is consistent with the approved Imfinzi dosing in extensive-stage small cell lung cancer (ES-SCLC) and once approved, will be available to patients with locally advanced, unresectable NSCLC weighing more than 30kg.

https://www.investegate.co.uk/astrazene ... 00086753I/

[monabri]

https://www.fool.co.uk/investing/2020/1 ... xion-deal/

Errr, let's hope not !!

(I'm surprised that no one at The Fool picked up on the AZN price)