What are they waiting for ?

[ikahan]

Dr Brian Koffman made available to us a very powerful article written by Dr Adrian Warnock about prophylactic mAbs given to those that did not respond to the vaccines

bloodcanceruncensored.com/i...

[Jm954 Administrator]

Apparently, 'they' are waiting for the results of trials. It seems that the impression is that the UK government is delaying accepting monoclonals for some political reason. We haven't seen any evidence that this is the case.

It may be that the AZ trial results have not been as successful on immune compromised patients as had been hoped, but the company is being very tight lipped about it. They've said that they will publish results as soon as they can, but have given no date. In any case, it would still need to go for approval, so it would not be a solution in the short term.

In February the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients who test positive for SARS-CoV-2 and who are at high risk for progressing to severe COVID-19. The authorized use includes treatment for those who are 65 years of age or older or who have certain chronic medical conditions.

In a clinical trial of patients with COVID-19 at high risk for disease progression, a single intravenous infusion of bamlanivimab and etesevimab administered together significantly reduced COVID-19-related hospitalization and death during 29 days of follow-up compared to placebo. The safety and effectiveness of this investigational therapy for use in the treatment of COVID-19 continue to be evaluated.

NOTE: Bamlanivimab and etesevimab are not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19. Treatment with bamlanivimab and etesevimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.

There is a lot more to know and understand about these treatments and how they should be best deployed to support vulnerable patients. If you need treatment there may be a monoclonal antibody clinical trial available to you.

Jackie

[mrsjsmith in reply to Jm954]

Thank you for your clear response Jackie.

Colette

[DebKat999 in reply to Jm954]

I would also like to thank you for this very informed response Jackie.

Debbie

[ikahan in reply to Jm954]

Dr Warnock is saying that we should start using these mAbs prophylactically, before exposure to COVID, for immunocompromised patients who did not respond to the vaccine. He argues that this is the right thing to do and will save lives, even though the clinical trials on pre-exposure prophylaxis with immunocompromised patients have not yet been completed.

…”the RECOVERY trial reported crucial and encouraging results. It shows that the Regeneron man-made monoclonal antibodies against COVID19 saves lives in infected patients who have not made antibodies themselves. A reduction in mortality in hospitalised patients of a fifth is VERY worth having.

This result is NOT unexpected and to be honest I personally would have argued that this study was unethical to perform as the data already strongly suggested this would be the outcome a year ago as this review I wrote last June shows. Although the data then suggested EARLY use was more important. This is because the data suggests that giving this to outpatients before they get sick enough to go into hospital is MUCH MORE effective.”

This article has given some hope that there is a way out of this interminable lockdown for CLL patients without Covid protection from Abs.

[Justasheet1 in reply to ikahan]

ika,

You do know that Dr Warnock is the one and only AdrianUK, who used to be a frequent poster on this forum.

Jeff

[Newdawn Administrator in reply to ikahan]

I think it’s important to point out that Adrian (who was a member on here for several years and is a CLL patient) stresses on his site that he doesn’t write in a medical capacity. He’s not a haematologist and gives his view from an informed patient’s perspective not as a medical advisor. This may be his strong view but as Jackie has explained, ‘the safety and effectiveness of this investigational therapy for use in the treatment of COVID-19 continue to be evaluated.’

Newdawn

[Jm954 Administrator in reply to ikahan]

I would like to see some longitudinal studies to establish how effective the antibody is over a period of time before this is adopted. Most people who have ivig have it every month or every other month so I'm not sure how long these antibodies would last and be effective. It would be wrong to give people the hope and illusion that they were protected when they were not.

As many of the posts here have stated, antibodies are only one element of immunity and these infused antibodies do nothing to develop a T cell response which is also very important.

I'm not saying the antibodies are not worth having but that we don't know yet. I think Adrian is extrapolating and perhaps offering false hope, when in fact we simply don't know. Is there a negative to receiving these antibodies? Again, we don't know, I'm just trying to keep an open mind and some balance to the discussions.

Jeff has also pointed out that these antibodies are not effective against the new variants.

Jackie

[ikahan in reply to Jm954]

The Astrazeneca AZD 7442 is long lasting , they say one year.

Also my husband who has developed zero Abs to the Moderna vaccine had a positive T detect test. So just b/c you don't have Abs doesn't mean you did not get a T cell response

[AussieNeil Partner Administrator in reply to ikahan]

I take that long lasting mention is in respect to how long the AZD 7442 remains circulating in the blood stream, not how long it remains effective against COVID-19, more specifically against variants that probably weren't present a year ago. Per:

healthunlocked.com/cllsuppo... "The Office of National Statistics (ONS) is one of the most reliable and independent sources of data we have in the UK. Each week they randomly sample a proportion of the population and make an estimate of the prevalence of infection. The latest is that more than 150,000 people across the UK contracted Covid -19 in the week ending 19th June. This is the highest figure since the easing of lockdown restrictions in April. Ninety five percent of cases are of the delta variant first identified in India."

I'd be thrilled if access to monoclonal antibodies freed us from our current restrictions from social involvement, but we need to be sure that they work with current variants, or we risk vulnerable people falsely assuming they are protected and sadly we know how that can end .

Per: en.wikipedia.org/wiki/SARS-... the delta variant "was first detected in India in late 2020.[2][3] The World Health Organization (WHO) named it the Delta variant on 31 May 2021."

In the UK, the delta variant was only reclassified from a Variant of Interest to a Variant of Concern by Public Health England (PHE) on 7th of May this year, barely 2 months ago:

gov.uk/government/news/conf...

"VUI-21APR-02 reclassified as a Variant of Concern (VOC)

Following a rise in cases in the UK and evidence of community transmission, PHE has reclassified VUI-21APR-02 (B.1.617.2, classified as a Variant Under Investigation (VUI) on 28 April) as a Variant of Concern (VOC), now known as VOC-21APR-02."

Neil

[bennevisplace in reply to AussieNeil]

"AZD7442 is a combination of two LAABs derived from convalescent patients after SARS-CoV-2 infection. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the LAABs were optimised by AstraZeneca with half-life extension and reduced Fc receptor binding. The half-life extended LAABs should afford six to 12 months of protection from COVID-19. The reduced Fc receptor binding aims to minimise the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease." astrazeneca.com/media-centr...

[Jm954 Administrator in reply to ikahan]

That's exactly what I was saying about the T cells etc.

I'm not sure how they can say the Astrazeneca AZD 7442 lasts over a year when it hasn't even been around that long! As I said, we need more studies to establish some scientific and medical facts and information.

[bennevisplace in reply to Jm954]

I am in the AZ Provent trial and back in April the study medic was hinting that they were nearly there. So either JM954 is right, AZ is sitting on the data, or the final few cases they needed to see didn't materialise as soon as they anticipated because of the success of the vaccine programme - including in many of the trial participants!

[ikahan in reply to bennevisplace]

The Provent trial is of uncertain relevance to CLL patients. Subjects in the Provent trial have not had the vaccine. The intervention group will get the monoclonal antibodies, but this won’t provide the potential T cell response that the vaccine confers, so it’s not clear if the monoclonal antibody will be as effective as the vaccine. Also, I wouldn’t be surprised if a significant number of people in both the intervention and placebo groups went and got the vaccine. I would….

For CLL patients who haven’t had an antibody response to the vaccine, the hope is that the monoclonal antibodies will give them antibody protection for up to a year, while the vaccine will give a T cell response even in the absence of an antibody response.

I would imagine that a clinical trial is being planned to look at the effectiveness of monoclonal antibodies as pre-exposure prophylaxis in patients who didn’t respond to the vaccine.

[bennevisplace in reply to ikahan]

When invited for vaccination, participants in the Provent trial were permitted to unblind. I imagine most of those on placebo went ahead and got vaccinated. I did.

For immunocompromised, it's not a question of either mAbs or vaccine. My choice would be a shot of Moderna, another of the modified AZ vaccine, a shot of AZ's mAb and another of GSK-VIR's. And see you this time next year.

[ikahan in reply to bennevisplace]

Yes, for immunocompromised that did not respond to the vaccine the mAb cocktails will hopefullybe used to supplement the Covid vaccines

[bennevisplace in reply to Jm954]

See my reply to Neil above.

[JigFettler Volunteer in reply to Jm954]

Thank you Jackie - very helpful explanations.

I have one niggling concern - and dont know if it is known...

BUT

Would the use of monoclonal Covid antibodies used prophylacticly negate or in anyway impede the effect of a Covid vaccine used subsequently?

Jig

[Jm954 Administrator in reply to ikahan]

"the data suggests that giving this to outpatients before they get sick enough to go into hospital is MUCH MORE effective.”

This poses an ethical dilemma too. How do doctors know which patients are likely to end up in hospital. There would need to be a validated way of assessing and predicting which patients will progress and targeting treatment at them as it would be completely unaffordable to give it to everyone . Is there any harm that can come from the antibodies themselves?

Even being a CLL patient does not mean that you will be hospitalised and we have had reports on this site of asymptotic covid infected CLL patients.

That is why more data and information is needed before even EAMS will consider it as a therapeutic intervention.

[bennevisplace in reply to Jm954]

Your italicised quote above is supported by very recent evidence, see healthunlocked.com/cllsuppo...

I don't see the ethical dilemma though.

Given the evidence that anti-Covid mAbs are generally more effective

1. in seronegative, compared with seropositive in-patients

2. when given to outpatients or exposed pre-symptomatics, compared with in-patients

and given the evidence that blood cancer patients and other immunocompromised people are at much higher risk of dying if infected,

it's reasonable to assume that this identifiable antibody-deficient group is the stand-out candidate for mAbs in early intervention or prophylaxis. The main problem as I see it is the paucity of direct evidence for the assumed benefit.

Perhaps someone else has cost info for REGEN-COV2?

For AZD7442 it was reported that the US government ordered 1/2 million doses, total value $205 million. From which we can guess that a substantial NHS order (per earlier reports of UK government commitment to 1 million doses) would work out at £250-300 per dose. In the scheme of things not prohibitive. But government would have to be sure it's money well spent. Like they did with Test n Trace 😂

[AussieNeil Partner Administrator in reply to bennevisplace]

I would say that the effectiveness of Test and Trace has been well and truly proven in Australia and New Zealand, with just 910 and 26 deaths from COVID-19 infections respectively. It was a confirmation failure in Test and Trace that led to Australia having 820 (90%) of those 920 deaths in the state of Victoria with just 26% of the country's population.

covid19data.com.au/states-a...

Due to the exponential nature of infection growth, a government has to act extremely quickly to introduce a targeted lock-down when infection numbers rise faster than the test and trace team can manage. That lock-down only needs to be for a week or two, providing time for the test and trace team to catch up and limited to the infected area(s) - again determined by test and trace team. Victoria needed a very long hard lock-down of 112 days to regain control. Getting this process working well isn't easy. Very few countries have managed it.

Unfortunately the increased infectiousness of the delta variant is proving extremely challenging to test and trace. Australia now has a record number of new cases per day. Will targeted lock-downs and state border closures work this time? The Australian public thinks no, with toilet paper aisles again stripped bare! It's also widely acknowledged that Australian governments were too complacent with their roll outs of vaccinations and now we may be about to pay the price.

covid19data.com.au/vaccines

Neil

[Justasheet1 in reply to Jm954]

Jackie,

Bam and Estes are no longer being infused in the US due to the new variants.

Jeff

[bennevisplace in reply to Jm954]

Jackie, I'm with you on the first part of your reply and will add to that below.

Just to point out though, "The U.S. government will pause distribution of the monoclonal antibodies bamlanivimab and etesevimab, authorized for high-risk COVID-19 outpatients, citing poor performance against variants, health officials announced on Friday". medpagetoday.com/infectious...

Sorry point covered by Jeff above.

[bennevisplace]

Yes, it's clinical data we are really waiting for, and for drug companies to apply to the UK regulator. AFAIK none has.

The UK does have a scheme granting early access to medicines, EAMS.

"The scheme was introduced by the MHRA to make it possible for promising unlicensed drugs or treatments to be made available to patients sooner, before the marketing approval stage. These medicines may be part of ongoing research, so there is a chance the medication could have unknown side effects or may not be effective. The full results from the Phase III trial of the medicine may also not be known at this stage.

The scheme requires drug companies with promising compounds to apply for a two-stage process, during which the drug must be designated as a ‘Promising Innovative Medicine’ based on available preclinical and clinical data, and obtain ‘Scientific Opinion’ on the risk:benefit balance based mainly on Phase III data (or Phase II in exceptional circumstances)". mndassociation.org/app/uplo...

And some temporary relaxations are in place to streamline applications gov.uk/guidance/mhra-regula...

It's all very well to demand MONOCLONALS NOW! But personally I think RECOVERY doesn't make a strong enough case to sway 'Scientific Opinion' and realistically all we can ask of UK government at this point is to (re)affirm its commitment to funding NHS use of Covid-targeted monoclonal antibodies in immunocompromised patients IF they become available. I'm not sure we're ever going to see Regen-Cov2 here. Sovotrimab, AZ7442 - maybe at some stage.

[Jm954 Administrator in reply to bennevisplace]

Agreed

[Luap001]

Let’s also not discount treatments that can save lives of those who become COVID infected. I first heard of Invermectin in this context from a study in Australia over a year ago! And now a meta analysis out of The UK earlier this year:

researchgate.net/publicatio...

And soon to take place is a study of Invermectin at Oxford.

Some of you have heard me extol my experience using Hesperidin in prior posts which I continue to rely upon as a prophylactic (started in February of last year). There is a study evaluating it as a treatment that has recently been completed in Canada. Hopefully it will be published. I take 500mg 3x daily whereas the study used 500mg twice daily.

Anyway, you have choices besides vaccines and these can be overlooked given the commingling of politics and science. And these choices are especially good news if you cannot mount an antibody response. I hope the prophylactic use of antibodies will also become part of our arsenal. But for those who don’t want (or cannot afford) to wait…