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GPs to handle referrals for ‘promising’ new IV treatment for Covid


health body replaces PHE


GPs could soon begin referring Covid-positive patients for a ‘promising’ new IV treatment designed to reduce the risk of severe illness and death, NHS England has said.  

In a letter to integrated care systems last week (15 June), NHS England said neutralising monoclonal antibodies have now been identified as a ‘potentially promising treatment’ against Covid, and that these laboratory-produced drugs could be offered to patients ‘as early as summer 2021’.

ICSs will therefore need to set up Covid monoclonal antibody delivery units (CMDUs), with contact and booking arrangements going through ‘referrals mainly from general practice and NHS111’, according to the letter.

The units may be ‘a mixture of community outreach, Covid positive hospital outpatient capacity or use of Covid assessment centres or other clinic facilities’, it said. 

The services will need to be able to deliver the drug to adults and ‘potentially’ children aged over 12, and initial treatments will need to be based on IV administration, as most of the research has been based on this method, it added. 

Monoclonal antibodies, which are artificially produced in laboratories, are injected directly into patients and are designed to mimic the immune system’s ability to fight off harmful antigens such as viruses. 

The UK RECOVERY trial recently found that REGEN-COV drug – a combination of two antiviral monoclonal antibodies – reduces the risk of death from Covid by a fifth in people who are unable to mount a natural antibody response of their own. In its study of 9,785 patients who were hospitalised due to Covid, it found that roughly a third did not have natural antibodies. 

The NHS England letter said: ‘Neutralising monoclonal antibodies have now been identified as a potentially promising treatment. Marketing authorisation by the MHRA and a clinical commissioning policy have not yet been determined but there is a potential for nMABs to be offered as a treatment to prioritised cohorts within the NHS as early as Summer 2021. 

‘Integrated care systems (ICSs) are by this letter therefore now being asked to identify intravenous (IV) infusion service options and plan capacity to meet potential demand ahead of a potential roll out of neutralising monoclonal antibodies as a treatment for Covid-19.’

In terms of funding, NHS England said: ‘Local systems are asked to identify resources to deliver this activity from within local funding envelopes, in line with other Covid response activity’.

NHS England chief executive Sir Simon Stevens repeated the call for health services to prepare to deliver monoclonal antibody treatments in the coming months while speaking at the NHS Confederation conference on Tuesday.

He said: ‘Today, I’m asking the health service to gear up for what is likely to be a new category of treatments – so-called self-neutralising monoclonal antibodies, which are potentially going to become available to us in the next several months. 

‘We are setting out our set of asks around how to bring that about in each integrated care system so that as and when those treatments become available to us, they can immediately begin to be deployed.’

He added that patients will be infused with the treatment ‘before they are hospitalised – typically within a three day window from the date of infection’. 

Earlier this year, the Government announced that Tocilizumab – an anti-inflammatory monoclonal antibody usually used for treating rheumatoid arthritis – would be used to treat patients hospitalised due to Covid-19, after the RECOVERY trial showed it could help reduce mortality by 14% and time spent in hospital.

In April, the Government launched a bid to identify antiviral drugs that patients can take at home when they have been diagnosed with, or exposed to, Covid.

READERS' COMMENTS [2]

Richard Mitchell 22 June, 2021 3:13 pm

All smells like tamiflu to me!

Keith M Laycock 22 June, 2021 6:33 pm

The bottom-line is being unable determine the truth: – Attached is a medical news article from the Canadian HealhCare Network commenting on the Recovery trial & the REN-GOV drug combo (casirivimab & imdevimab). The added comments / questions (in brackets) were previously entered to share with other colleagues.

Statements extracted from the article: –
a. ‘not authorised for use in patients who hosptalised’
b. ‘may be associated with worse clinical outcomes when administered to hospitalised patients’

In the setting that: – Only those who are sick enough to require hospitalisation (whether they are admitted or not) are at risk of death and those at risk of death (as per RECOVERY) do not benefit – only those who are ‘mildly or moderately’ unwell are ‘questionably’ benefitted.

Canadian HealthCare Network Article: – June 2021.

https://www.canadianhealthcarenetwork.ca/monoclonal-antibody-combination-approved-mildmoderate-covid-19?oly_enc_id=9453D6024034E0S

Monoclonal antibody combination approved for mild/moderate COVID-19
Health Canada grants interim authorization to Roche’s casirivimab and imdevimab.

Health Canada has issued an Interim Order authorization for casirivimab and imdevimab for the treatment of mild to moderate COVID-19 in adults and adolescents (≥ 12 years of age, weighing at least 40 kg) who are at high-risk for progressing to hospitalization and/or death.1,2

(??????? – and why does a mild viral infection need any treatment??? and why would a mild attack be ‘high-risk ???)

Interim authorization for the monoclonal antibody combination was granted pending the results of trials to verify the clinical benefits of this therapy. Early clinical trial results suggest that the drug combination reduces the rate of COVID-19-related hospitalization or death by about 70%.2

(70% of what number? and ‘trials not complete to verify benefits ????)

Patients considered to be at high risk of contracting severe COVID-19, and therefore potential candidates for casirivimab and imdevimab, include those with one or more of the following risk factors:

≥ 50 years of age, irrespective of comorbidities …..
(so that must mean that all over 50 yrs ‘are at high- risk of hospital or death – which is, of course, not true)

≥ 18 years of age and one of the following comorbidities: obesity, cardiovascular disease (including hypertension), chronic lung disease, diabetes, chronic kidney disease, chronic liver disease, or immunosuppression.2

Casirivimab and imdevimab are not authorized for use in patients who are hospitalized due to COVID-19, those who require oxygen therapy due to COVID-19, or patients on chronic oxygen therapy (due to underlying non-COVID-19 related comorbidity) who require an increase in baseline oxygen flow rate due to COVID-19.

(Just think about that in the overall context of the information – the flawed thinking is obvious)

Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.2
(!!!!!! ??????)

Action Casirivimab and imdevimab are two recombinant human monoclonal antibodies that target the spike protein of SARS-CoV-2. Casirivimab and imdevimab bind to the spike protein and block its interaction with angiotensin-converting enzyme 2 (ACE2), leading to inhibition of infection of host cells.2

(but if you have a diagnosis of Covid – which is the disease, not asymptomatic SARS2 infection – the host cell has already been breached by the Spike protein route)

Dosage Casirivimab and imdevimab are administered together by intravenous (IV) infusion. The combination should be given as soon as possible after the onset of symptoms and after a positive result is obtained using a direct SARS-CoV-2 validated testing method to confirm the diagnosis of COVID-19.2
The recommended dosage for adults and adolescents (≥ 12 years of age, weighing at least 40 kg) is 1200 mg of casirivimab and 1200 mg of imdevimab given together as a single IV infusion (after dilution in a 250 mL bag of 0.9% sodium chloride injection). The infusion is administered over at least one hour (maximum infusion rate 270 mL/hr).2
Adverse effects Serious hypersensitivity reactions, including anaphylaxis, have been reported. Patients should be monitored during the infusion and for at least one hour after the infusion ends. Signs and symptoms of infusion-related reactions may include fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash (including urticaria), pruritus, myalgia, dizziness, fatigue and diaphoresis. If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care. The monoclonal antibody combination should only be administered in settings where there is immediate access to medications to treat a severe infusion reaction or anaphylaxis.2
(That should help you feel better especially when you weren’t feeling all that bad in the first place – the majority)
Product information for casirivimab and/or imdevimab warns that circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies.2

(And we told that the variants have taken over anyway – of course, the neither patient nor the doc has any idea which one they have unless all patients are sequenced which, even if logistically possible, would hardly fit the criterium of give ’as soon as possible’)

Drug interactions No interaction studies have been performed. However, casirivimab and imdevimab are not renally excreted or metabolized by CYP450 enzymes. As a result, interactions are unlikely to occur with concomitant medications that are renally excreted or that are substrates, inducers or inhibitors of CYP450 enzymes.2

You can read the rest if you want……… K

Supplied/Storage Casirivimab and imdevimab are expected to be available from Hoffmann-La Roche in July 2021. They will be supplied in cartons containing two single-dose vials per package: one vial of 1332 mg/11.1 mL of casirivimab and one vial of 1332 mg/11.1 mL imdevimab, or one vial of 300 mg/2.5 mL of casirivimab and one vial of 300 mg/2.5 mL imdevimab. Both products should be stored in the refrigerator (2°C to 8°C) in the original carton to protect from light.2
Other monoclonal antibodies approved or under consideration for COVID-19
Bamlanivimab for injection (Eli Lilly), an anti-SARS-CoV-2 spike protein monoclonal antibody, received interim authorization by Health Canada on Nov. 20, 2020. It is indicated for the treatment of adults and adolescents (≥ 12 years of age, weighing 40 kg or more) with mild to moderate COVID-19, who are at high risk of progressing to severe COVID-19 illness and/or hospitalization.3
In late April 2021, Health Canada issued an advisory warning about the potential risk of bamlanivimab treatment failure due to circulation of resistant SARS-CoV-2 variants. The drug showed reduced in vitro activity against SARS-CoV-2 variants with the E484K (e.g., South Africa or Brazil origin) and L452R (e.g., California origin) mutations. As a result, healthcare professionals are advised to take the epidemiology of variants into consideration before empiric use of bamlanivimab as single monoclonal antibody therapy, and to use bamlanivimab only in regions where there is a known or confirmed low prevalence of lineages containing E484K and/or L452R SARS-CoV-2 variants.4
Other monoclonal antibodies currently under consideration for approval by Health Canada include regdanvimab (Celltrion HealthCare), leronlimab (CytoDyn), bamlanivimab and etesevimab (Eli Lilly) and sotrovimab (GlaxoSmithKline).5 More detailed information on some of these monoclonal antibodies is freely available from The Medical Letter.6
References
1. Hoffmann-La Roche Ltd. Health Canada grants Interim Order authorization for casirivimab and imdevimab for the treatment of mild to moderate COVID-19. https://www.newswire.ca/news-releases/health-canada-grants-interim-order-authorization-for-casirivimab-and-imdevimab-for-the-treatment-of-mild-to-moderate-covid-19-812156971.html (accessed June 17, 2021).
2. Hoffmann-La Roche Ltd. Casirivimab and imdevimab for injection (casirivimab and imdevimab) product monograph. Mississauga, ON; June 9, 2021. https://pdf.hres.ca/dpd_pm/00061474.PDF (accessed June 17, 2021).
3. Eli Lilly Canada Inc. Bamlanivimab for injection product monograph. Toronto, ON; April 14, 2021. https://pdf.hres.ca/dpd_pm/00060539.PDF (accessed June 17, 2021).
4. Health Canada. Bamlanivimab – potential risk of treatment failure due to circulation of resistant SARS-CoV-2 variants. https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2021/75503a-eng.php (accessed June 17, 2021).
5. Health Canada. Drug and vaccine authorizations for COVID-19: list of applications received. https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/authorization/applications.html (accessed June 17, 2021).
6. Anon. Drugs for COVID-19. Med Lett Drugs Ther 2021; June 17. https://secure.medicalletter.org/drugs-for-covid-19 (accessed June 17, 2021)

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