Coronavirus Notebook: UK Rolls Out Ronapreve To Hospitalized Patients, Drug Safety Unit Reviews mRNA Vaccine Heart Inflammation Link
Executive Summary
Pressure is growing on richer countries to share their excess vaccine doses, and the European Parliament has passed legislation intended to strengthen the EU’s health security framework and make joint vaccine procurement more transparent.
The UK is this week beginning the rollout of Roche Holding AG/Regeneron Pharmaceuticals, Inc.’s monoclonal antibody (MAb) combination, Ronapreve (casirivimab and imdevimab), initially for patients in hospital who have not mounted an antibody response to COVID-19, either through exposure to the virus or from vaccination.
Ronapreve was granted a conditional marketing authorization (CMA) by the UK regulator, the MHRA, in August, as the first combination MAb product for use in the treatment and post-exposure prophylaxis of acute COVID-19 infection in the UK. (Also see "UK Approves Regeneron/Roche MAb Cocktail For COVID-19" - Pink Sheet, 20 Aug, 2021.)
The government said it had secured enough Ronapreve to meet patient needs in the four nations of the UK, and that guidance was being sent to clinicians so that they could “begin prescribing the treatment as soon as possible.”
Ronapreve will be used to treat patients without antibodies to the SARS-CoV-2 virus who are aged either 50 years or over or who are aged 12 to 49 and considered to be immunocompromised – for example, those who have certain cancers or autoimmune diseases. Antibody testing will first be used to determine which patients are seronegative and will therefore receive the treatment, according to the department of health and social care.
Paul McManus, COVID-19 lead at Roche Products Ltd, said Ronapreve was “the first dedicated medicine developed for COVID-19 to receive marketing authorization from the MHRA, representing a significant milestone in how the NHS [National Health Service] is able to fight this disease.”
He said Roche would “continue to collaborate with partners to identify and investigate multiple options that may help different groups of patients.”
The CMA was based mainly on results from two Phase III randomized, double-blinded, placebo-controlled clinical trials, according to the Ronapreve product information. COV-2067 evaluated Ronapreve for the treatment of subjects with COVID-19 who were not hospitalized, and COV-2069 studied the combination product for the prevention of COVID-19 in household contacts of individuals infected with SARS-CoV-2 (index case).
The safety profile of IV administration of Ronapreve was primarily based on the pooled safety data analysis of the COV-2067 study, while for the subcutaneous route, it was based mainly on the COV-2069 study results. Expanded analysis has also been performed on safety data from supportive studies (COV-20145 and HV-2093).
Reported adverse drug reactions identified from the clinical development program related mainly to hypersensitivity reactions including infusion-related reactions and injection site reactions.
UK Safety Unit Reviews Vaccine Heart Inflammation Link
On the vaccine front, the UK’s independent Drug Safety Research Unit has reviewed the available data on heart inflammation following the administration of COVID-19 vaccines and concluded that while the condition is “very rare and generally mild,” further monitoring and study are needed.
The DSRU compared data from the UK, the US and Europe on the rates of myocarditis and pericarditis reported after vaccination with the mRNA vaccines from
Pfizer Inc./BioNTech SE and Moderna, Inc.. It found that these events were very rare and most cases were mild, with vaccinees making “a full recovery.”
In the UK, as of 4 August 2021, there were 165 reported myocarditis events and 140 pericarditis events after the Pfizer/BioNTech vaccine, and two of these events were fatal, the DSRU noted. “This equates to approximately 7.93 cases of myocarditis and 6.73 cases of pericarditis per million vaccinees who had received at least one dose of the Pfizer/BioNTech vaccine.”
Among those who received the Moderna vaccine, there were 29 reports of myocarditis and 25 reports of pericarditis, none of which were fatal. “This equates to 2.07 cases of myocarditis and 1.79 cases of pericarditis per million vaccinees.”
The results echo previous findings that men and people under 30 years of age were more likely to experience myocarditis or pericarditis after being given one of these vaccines, according to the DSRU.
However, only data from spontaneous reporting are available so far, which means that cases might be missed or misdiagnosed, and “there is little extra information to help researchers and doctors understand who is more at risk,” it said. “In addition, it’s not possible to gauge incidence rates of these events by relying exclusively on spontaneous reporting.”
While passive spontaneously reported information is very good for detecting signals, “like all pharmacovigilance methods, it has limitations,” said the DSRU’s Saad Shakir, who led the study. “With proactive research, we can understand who is at greater risk and why. And we can introduce measures to protect them.”
Only mRNA vaccines have been approved for use in children from 12 years of age, and “as vaccination programmes around the world progress into younger age groups, rates of myocarditis and pericarditis need to be monitored,” the unit added.
‘Share Those Vaccines’
On the global stage, pressure is growing on wealthier countries to share their excess vaccines with low- and middle-income countries (LMICs) before they expire.
In advance of the virtual COVID-19 summit to be convened by US president Joe Biden on 22 September on the fringes of the United Nations General Assembly, former UK prime minister Gordon Brown said a plan was needed to distribute these vaccines quickly.
He said he had sent Biden and other G7 leaders a copy of research by the scientific information and analytics firm Airfinity showing that 100 million vaccines currently being stockpiled in wealthier countries risked reaching their expiry data in December without ever being used.
"It would be a profound and collective political tragedy if this summit misses the opportunity to act with doses transferred immediately to poorer countries" – former UK prime minister Gordon Brown
Brown, who has just been appointed the World Health Organization's Ambassador for global health financing, said it would be “a profound and collective political tragedy if this summit misses the opportunity to act with doses transferred immediately to poorer countries."
The medical NGO, Médecins Sans Frontières, said that with nearly five million lives lost because of COVID-19, high-income governments must “urgently do three things so we can turn a corner on this pandemic.”
For one thing, these countries had to “immediately redistribute their excess COVID-19 vaccines well before these doses expire” to LMICs that are dramatically lagging behind in vaccination coverage via the global COVAX Facility or regional procurement bodies, MSF said.
They must also “use all their power to compel pharmaceutical corporations to share mRNA technology and know-how with the World Health Organization’s COVID-19 mRNA Vaccine Technology Transfer Hub in South Africa, and to share technology and know-how to produce monoclonal antibody treatments."
Finally, MSF declared, all governments must support the proposed TRIPS waiver, which would “allow all governments to remove intellectual property barriers and increase supply and availability of COVID-19 treatments, diagnostics and vaccines during the pandemic, so that many more lives can be saved.”
More generally, the NGO said it was high time to examine the root causes of the access crisis during the pandemic: the “structural inequality in the global health system which concentrates decision-making power and ownership of lifesaving health technologies in the hands of a few powerful nations and their pharmaceutical corporations.”
It said that any mechanism aimed at improving the current pandemic response and future pandemic preparedness and response “should not repeat the mistakes made during COVID-19 to date, and be firmly rooted in multilateral cooperation with clear accountability for high-income governments and pharmaceutical corporations in particular.”
EP OKs Legislation On Future Health Threats
The need to prepare for future health emergencies has also been emphasized by the European Parliament, which last week said it was ready to negotiate with the EU member states to strengthen the bloc’s disease prevention and control framework and work jointly on tackling cross-border health threats.
The parliament adopted two pieces of draft legislation put forward by the European Commission that are intended to build up a new health security framework, which itself is part of an effort to create a European Health Union.
One of the legislative proposals would extend the mandate of the European Centre for Disease Prevention and Control (ECDC), and was adopted by the parliament with 598 votes in favor, 84 against and 13 abstentions.
Members of the parliament (MEPs) said that the EU member states should “develop national preparedness and response plans, and provide timely, comparable and high quality data.” They also wanted to make sure that the ECDC’s mandate was extended beyond communicable diseases to cover major non-communicable diseases such as cardiovascular and respiratory diseases, cancer, diabetes and mental illness.
The second legislative proposal would strengthen the EU’s crisis prevention, preparedness and response when addressing future serious cross-border health threats, and was adopted with 594 votes in favor, 85 against and 16 abstentions.
MEPs said the COVID-19 crisis had shown that further work at EU level was needed to support cooperation between member states, in particular the border regions. The adopted text also calls for clearer procedures and more transparency for EU joint procurement activities and related purchase agreements for vaccines and other medical products.
MEP Véronique Trillet-Lenoir said that the aim of “One Health” in European policies “must guide our entire crisis anticipation and management system. The COVID-19 crisis shows how a public health issue can affect the proper functioning of every part of European society.”
She said she fully supported moves to ensure that a joint purchasing procedure for medical products became standard practice. “As far as negotiating with industry is concerned, the EU is stronger when it speaks with one voice, on behalf of all member states,” she added.
Member state health ministers are due to discuss the EU's preparedness for and response to future health threats, as well as the availability of and access to medicines, at an informal videoconference on 12 October.