{"id":38051,"date":"2020-06-01T07:43:02","date_gmt":"2020-06-01T07:43:02","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=38051"},"modified":"2023-10-11T16:31:35","modified_gmt":"2023-10-11T16:31:35","slug":"mhra-approves-remdesivir-for-expanded-access-in-the-uk","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/38051","title":{"rendered":"UK access to remdesivir approved: but MHRA criteria exclude some who could benefit"},"content":{"rendered":"<p class=\"HTBsubhead3authorcredit\"><strong><span lang=\"EN-US\"><img loading=\"lazy\" decoding=\"async\" class=\" alignright\" src=\"https:\/\/i-base.info\/wp-content\/uploads\/2020\/03\/COVID-19-graphic.png\" width=\"231\" height=\"142\" \/>Simon Collins, HIV i-Base<\/span><\/strong><\/p>\n<p class=\"HTBBODYFIRST\"><strong><span lang=\"EN-US\">On 26 May 2020 the Medicines and Healthcare products Regulatory Agency (MHRA) issued a press release and guidelines to outline criteria for UK access to remdesivir, the first drug to be approved in the US to treat COVID-19. [1]<\/span><\/strong><\/p>\n<p class=\"gmail-HTBBODYtext\"><span lang=\"EN-US\">However, some people who could benefit are not included. Also, ongoing COVID-19 studies should also now include remdesivir as part of the new standard of care. This is a principle from community engagement in HIV research.<\/span><\/p>\n<p class=\"gmail-HTBBODYtext\"><span lang=\"EN-US\">Access to remdesivir\u00a0will use a programme that allows people with life-threatening illnesses to have early access to medicines that already have proven benefits but that are still going through full approval.<\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">To reach this stage an advisory group (the Commission on Human Medicines) has reviewed the available evidence and recommended that remdesivir is both effective and safe enough for early access. [2, 3]<\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The UK indication is for:<\/span><\/p>\n<ol>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">The treatment of adults and adolescents aged \u2265 12 years and weighing at least 40 kg hospitalised with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease.<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Severe disease is defined as an SpO2 \u2264 94% on room air or requiring supplemental oxygen or requiring non-invasive or invasive ventilation or extracorporeal membrane oxygenation (ECMO). <\/span><\/li>\n<\/ol>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">However the document then suggests than remdesivir should be more effective in earlier infection but also this should benefit those at higher risk, and that includes criteria for access. [4]<\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The criteria are listed below.<\/span><\/p>\n<p class=\"HTBBODYtext\"><b><span lang=\"EN-US\">Early access criteria<\/span><\/b><\/p>\n<ul>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Age 12 years or older on the date of starting treatment.<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Weight \u226540kg on the date of starting treatment.<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Creatinine clearance above 50 mL\/min (upper level defined).<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">AST\/ALT below 5 times upper limit of normal and no history of chronic liver disease <\/span>defined as Child-Pugh C.<\/li>\n<\/ul>\n<p class=\"HTBBODYtext\"><b><span lang=\"EN-US\">Risk score<\/span><\/b><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Access dependent on having at least four of the following factors (or three <\/span>if the radiographic severity score threshold is reached).<\/p>\n<ul>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Radiographic severity score &gt;3.<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Male gender.<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Non-white ethnicity. <\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Diabetes.<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Hypertension.<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Neutrophils &gt;8.0 10 \/L. <\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Age &gt;40 years.<\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">CRP &gt;40 mg\/L.<\/span><\/li>\n<\/ul>\n<p><b><span lang=\"EN-US\">Diagnostic criteria<\/span><\/b><\/p>\n<ul>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Less than 10 days from onset of symptoms <\/span><\/li>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">Hospitalised with SARS-CoV-2 infection confirmed by PCR collected in preceding 72 hours <\/span><\/li>\n<\/ul>\n<p class=\"HTBBODYindent\"><b>Illness severity and organ support criteria <\/b><\/p>\n<ul>\n<li class=\"HTBBODYindent\">Discussion about the eligibility for escalation to critical care including invasive mechanical ventilation, multi-organ support and CPR should be considered through shared decision making in line with the NICE guidance <a href=\"https:\/\/www.nice.org.uk\/guidance\/ng159\" rel=\"noopener noreferrer\">NG159 (using the Clinical Frailty Score)<\/a>. [5]\u00a0Some people not eligible for escalation may be suitable for access to remdesivir as determined by mutildisciplinary assessment.<\/li>\n<li class=\"HTBBODYindent\">Patient who require FiO2 \u2265 0.4% to maintain O2 sats &gt;94% with standard oxygen therapy (Hudson mask) measured on two occasions at least 1 hour apart; OR who are within 24h of commencing CPAP or HFNO2 to maintain O2 sats &gt;94% and have not been previously mechanically ventilated for treatment of COVID-19<\/li>\n<li class=\"HTBBODYindent\">Not requiring invasive mechanical ventilation, ECMO, cardiovascular support (pressor, inotrope or mechanical) at the time of drug initiation. Those starting on the drug should continue if they subsequently need invasive mechanical ventilation. The evidence of benefit has not been demonstrated for those on ventilation. There may be some patients just starting on ventilation in the early phase of the infection who may be suitable for access to remdesivir as determined by mutildisciplinary assessment.<\/li>\n<\/ul>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Reporting safety and outcome data is a requirement for use of remdesivir.<\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Logistic details are outlined for each UK country but trusts will be allocated stock upfront. They will be able to preorder supplies based on caseload and expected need.<\/span><\/p>\n<h3 class=\"HTBcommenttitle\"><span lang=\"EN-US\">comment<\/span><\/h3>\n<p class=\"HTBBODYtext\"><strong><span lang=\"EN-US\">The early access to remdesivir is important. It should immediately improve the outcomes for many people who are ill with COVID-19. Even though the protocol requires people to be hospitalised, it should encourage people with confirmed COVID-19 to seek hospital treatment earlier.<\/span><\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong><span lang=\"EN-US\">Remdesivir has the potential to save lives and earlier access will improve the chance of better outcomes.<\/span><\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong>So whilst the data clearly show benefit of remdesivir in hospitalised patients, especially for those requiring supplemental oxygen therapy, there remains an issue of supply of remdesivir and therefore the need to prioritise sickest and \u2018most at risk\u2019 patients, and exclude patients likely to have poor outcomes.<\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong>The current criteria are justifiably stringent in this regard, and will, hopefully become less stringent, as supplies improve over the coming months (and cases hopefully reduce). \u00a0<\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong>There are, however, two criteria that deserve immediate attention. \u00a0<\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong>Patients who are thought unsuitable for \u2018escalation\u2019 or Intensive Care are excluded, unless an MDT decides that they are suitable. \u00a0Actually, this is exactly the group most likely to benefit, if there was a reasonable short to medium term prognosis from a general health point of view, since remdesivir could prevent both progression and the need for ventilatory support.<\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong>The second group that should be reconsidered is patients presenting beyond 10 days of symptom onset. \u00a0These people would also benefit from added anti-inflammatory therapy, however as the ACTT-1 trial showed, time from onset of symptoms was not an important factor for achieving primary outcome.<\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong>For patients needing mechanical ventilatory support\/ECMO there is clearly a need for added anti-inflammatory therapy.<\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong>Finally, all future studies of antiviral and anti-inflammatory or immunomodulatory therapy now need to consider remdesivir as the new \u2019standard of care\u2019 for comparison. <\/strong><\/p>\n<p class=\"HTBBODYtext\"><strong>Rapidly responding to advances in the standard of care was a basic principle of community engagement with HIV research and it is just as important for COVID-19.<\/strong><\/p>\n<p><strong>STOP PRESS: As this issue of HIV and COVID-19 was being finalised for distribution, Gilead issued a press release on the <b>SIMPLE-Moderate study. Top-line results showed that in moderate COVID-19 disease \u2013 those with pneumonia who do not require supplemental oxygen \u2013 a 5-day course of remdesivir led to greater clinical improvement than standard of care alone. [6]<\/b><\/strong><strong>\u00a0<\/strong><\/p>\n<p class=\"HTBreferences\"><span lang=\"EN-US\">References<\/span><\/p>\n<ol>\n<li class=\"HTBreferences\"><span lang=\"EN-US\">MHRA. <\/span>MHRA issues a scientific opinion for the first medicine to treat COVID-19 in the UK. (26 May 2020).<br \/>\n<b><\/b><a href=\"https:\/\/www.gov.uk\/government\/news\/mhra-supports-the-use-of-remdesivir-as-the-first-medicine-to-treat-covid-19-in-the-uk\" rel=\"noopener noreferrer\"><span lang=\"EN-US\">https:\/\/www.gov.uk\/government\/news\/mhra-supports-the-use-of-remdesivir-as-the-first-medicine-to-treat-covid-19-in-the-uk<\/span><\/a><\/li>\n<li class=\"HTBreferences\"><span lang=\"EN-US\">MHRA. Early access to medicines scheme (EAMS) scientific opinion: remdesivir in the treatment of patients hospitalised with suspected or laboratory-confirmed SARS-CoV-2 infection who meet the clinical criteria. <\/span>(26 May 2020).<br \/>\n<b><\/b><a href=\"https:\/\/www.gov.uk\/government\/publications\/early-access-to-medicines-scheme-eams-scientific-opinion-remdesivir-in-the-treatment-of-patients-hospitalised-with-suspected-or-laboratory-confirme\" rel=\"noopener noreferrer\"><span lang=\"EN-US\">https:\/\/www.gov.uk\/government\/publications\/early-access-to-medicines-scheme-eams-scientific-opinion-remdesivir-in-the-treatment-of-patients-hospitalised-with-suspected-or-laboratory-confirme<\/span><\/a><\/li>\n<li class=\"HTBreferences\"><span lang=\"EN-US\">Product information for healthcare professionals.<br \/>\n<\/span><a href=\"https:\/\/www.gov.uk\/government\/publications\/early-access-to-medicines-scheme-eams-scientific-opinion-remdesivir-in-the-treatment-of-patients-hospitalised-with-suspected-or-laboratory-confirme\" rel=\"noopener noreferrer\"><span lang=\"EN-US\">https:\/\/www.gov.uk\/government\/publications\/early-access-to-medicines-scheme-eams-scientific-opinion-remdesivir-in-the-treatment-of-patients-hospitalised-with-suspected-or-laboratory-confirme<\/span><\/a><span lang=\"EN-US\"> (web page)<\/span><span lang=\"EN-US\"><br \/>\n<a href=\"https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/887275\/EAMS__11972_0002__TP__HCP_Solution.pdf\" rel=\"noopener noreferrer\">https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/887275\/EAMS__11972_0002__TP__HCP_Solution.pdf<\/a> (PDF direct link) <\/span><\/li>\n<li class=\"HTBreferences\">COVID-19 Therapeutic Alert. Early Access to Medicines Scheme for remdesivir in the treatment of COVID-19. Implementation of the scheme and management of supply. CEM\/CMO\/2020\/025 Issue date: 26 May 2020<br \/>\n<a href=\"https:\/\/www.cas.mhra.gov.uk\/ViewandAcknowledgment\/ViewAlert.aspx?AlertID=103046\" rel=\"noopener noreferrer\">https:\/\/www.cas.mhra.gov.uk\/ViewandAcknowledgment\/ViewAlert.aspx?AlertID=103046<\/a> (web link)<br \/>\n<a href=\"https:\/\/www.cas.mhra.gov.uk\/ViewandAcknowledgment\/ViewAttachment.aspx?Attachment_id=103580\" rel=\"noopener noreferrer\">https:\/\/www.cas.mhra.gov.uk\/ViewandAcknowledgment\/ViewAttachment.aspx?Attachment_id=103580<\/a> (PDF download)<\/li>\n<li class=\"HTBreferences\">NICE. COVID-19 rapid guideline: critical care in adults.\u00a0<span class=\"prod-title\">NICE guideline [NG159].<\/span><wbr \/>\u00a0(<span class=\"published-date\">Last update\u00a0<time datetime=\"2020-04-29\">29 April 2020).<br \/>\n<\/time><\/span><a href=\"https:\/\/www.nice.org.uk\/guidance\/ng159\" rel=\"noopener noreferrer\">https:\/\/www.nice.org.uk\/guidance\/ng159<\/a><\/li>\n<li>Gilead press statement. Gilead announces results from phase 3 trial of remdesivir in patients with moderate COVID-19. (1 June 2020).<br \/>\n<a href=\"https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2020\/6\/gilead-announces-results-from-phase-3-trial-of-remdesivir-in-patients-with-moderate-covid-19\" rel=\"noopener noreferrer\">https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2020\/6\/gilead-announces-results-from-phase-3-trial-of-remdesivir-in-patients-with-moderate-covid-19<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Simon Collins, HIV i-Base On 26 May 2020 the Medicines and Healthcare products Regulatory Agency (MHRA) issued a press release and guidelines to outline criteria for UK access to remdesivir, the first drug to be approved in the US to &hellip;<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[286,278],"tags":[],"class_list":["post-38051","post","type-post","status-publish","format-standard","hentry","category-covid-19-treatment-access","category-covid-19"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38051","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=38051"}],"version-history":[{"count":2,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38051\/revisions"}],"predecessor-version":[{"id":46532,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38051\/revisions\/46532"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=38051"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=38051"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=38051"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}