Coronavirus Notebook: WHO Backs MAb Combo, EMA Assessing Moderna Booster Jab
Executive Summary
The COVID Moonshot project has received new funding for the open-source development of new candidate therapeutics, with results expected by the end of the year.
The prospects for using monoclonal antibodies as a treatment for people with SARS-CoV-2 infection in lower-income countries have received a boost after the World Health Organization gave its backing to the Regeneron Pharmaceuticals, Inc./Roche Holding AG combination product, casirivimab + imdevimab (REGN-COV2).
The WHO also suggested that the companies share the technology on the product to allow cheaper biosimilar versions to be produced.
In an update to its “living guideline” on COVID-19 therapeutics, published on 24 September, the WHO says the combination should be reserved for patients with non-severe infection who are at the highest risk of hospitalization, such as unvaccinated individuals or those who were older or immunosuppressed.
In non-severe patients, “casirivimab and imdevimab probably reduces the risk of hospitalization and duration of symptoms,” the guideline says, adding that the combination is “unlikely to have serious adverse effects, including allergic reactions.”
High Cost, Low Availability
In a statement, the WHO said that in view of “the high cost and low availability of the combination therapy,” the global health agency Unitaid was negotiating with Roche, “which is currently manufacturing the drug, for lower prices and equitable distribution across all regions, especially in low- and middle-income countries.”
The WHO said it was also in discussions with Roche for donation and distribution of the drug through the children’s charity UNICEF, in line with the organization’s allocation criteria. “WHO also calls for the sharing of technology to allow for the manufacturing of biosimilar versions so all patients who may need this treatment have access to it,” it added.
“In routine care of those with non-severe COVID-19, there is a lack of tools to reliably identify those at highest risk of hospitalization” – World Health Organization
But there are challenges associated with distribution of the combination product. The WHO’s guideline notes that “in routine care of those with non-severe COVID-19, there is a lack of tools to reliably identify those at highest risk of hospitalization.”
It said this clinical complexity, “combined with the limited availability of the drug and need for parenteral administration route for a group of patients who are typically cared for in the community, present a range of challenges for care that need to be addressed by health care systems.”
In order to scale up production of the combination antibody therapy, the WHO has issued a call for expressions of interest (EOIs) from manufacturers who might be interested in producing it under its prequalification process. The call was included in its fourth invitation for EOIs for COVID-19 therapeutics, which also covers products such as dexamethasone, tocilizumab and sarilumab, and was published on 21 September.
The organization also noted that partners in the Access to COVID-19 Tools (ACT) Accelerator were working with it on an equitable access framework for recommended COVID-19 therapeutics.
“Broader access commitments are needed from industry to ensure that pricing and supply conditions enable this product to reach all people” – Unitaid
Unitaid, which is hosted by the WHO, welcomed the updated guideline on casirivimab + imdevimab, saying that “the need to have effective treatments for COVID-19 has never been greater, with many countries around the world facing case surges driven by Delta and other variants. These surges are having a particularly devastating impact on low- and middle-income countries, which continue to have limited access to vaccines.”
Global, equitable access to new tools against COVID-19 was “crucial if we are to ensure that hard-won developments in the fight against the pandemic can reach all those who may benefit” in all settings, including in low- and middle-income countries, it declared.
In view of the challenges noted above, Unitaid said the WHO allocation criteria would be “critical in helping identify people who may benefit from this treatment.”
A proposed initial donation from Roche/Regeneron, to be managed by UNICEF, “could help meet immediate needs and ensure casirivimab/imdevimab reaches people who could benefit,” Unitaid declared.
“However, a limited donation – on its own – is not enough to ensure equitable, global access to lifesaving COVID-19 treatments,” it said. “Broader access commitments are needed from industry to ensure that pricing and supply conditions enable this product to reach all people regardless of where they live.”
The casirivimab + imdevimab combination and other MAb-based products are currently under rolling review at the European Medicines Agency, with opinions from its human medicines committee, the CHMP, expected for at least some of them by the end of October. (Also see "EU Decision Imminent On Comirnaty Booster, Data Expected On Use In 5-11 Year Olds" - Pink Sheet, 24 Sep, 2021.)
EMA Assessing Moderna Booster Dose
On the vaccines front, the EMA has begun evaluating a second application to approve a booster dose of an authorized COVID-19 vaccine, this time for Moderna’s Spikevax. The booster jab would be given at least six months after the second dose in people aged 12 years and older.
The CHMP will carry out an accelerated assessment of data on Spikevax submitted by Moderna, including results from an ongoing clinical trial. “Based on this review, the CHMP will recommend whether updates to the product information are appropriate,” the agency said, noting that it would “communicate the outcome of the assessment in due course.”
Earlier this month the EMA said it expected the CHMP to make a recommendation on whether to OK a booster dose of the Pfizer/BioNTech vaccine, Comirnaty, again for use at least six months after completion of the initial vaccination course. The agency is also expecting data on the use of Comirnaty in children aged five to 11 years. (Also see "EU Decision Imminent On Comirnaty Booster, Data Expected On Use In 5-11 Year Olds" - Pink Sheet, 24 Sep, 2021.)
Booster doses are designed to be administered to people who have completed their primary vaccination to restore immunological protection after it has waned. But their use is controversial given the fact that people in many countries around the world have still received either no vaccine or only the first dose.
The EMA and the European Centre for Disease Prevention and Control (ECDC) recently issued a statement saying that they “do not consider the need for COVID-19 vaccine booster doses to be urgent in the general population.” (Also see "Coronavirus Notebook: ‘No Urgent Need’ For Booster Vaccines, But EU & UK Advise Additional Doses In Immunocompromised" - Pink Sheet, 2 Sep, 2021.) Nonetheless, the EMA said it was evaluating booster applications “to ensure evidence is available to support further doses as necessary.” The EMA and ECDC also acknowledged that there was a case for giving additional vaccine doses to people with severely weakened immune systems who might not mount a sufficient response after the initial vaccination course.
Advice on how vaccinations should be given remains the prerogative of the national immunization technical advisory groups guiding the vaccination campaigns in each EU member state, the EMA noted.
COVID Moonshot Gets Cash Injection
The pharmaceutical industry’s development of COVID-19 vaccines and therapeutics may rely on work carried out in, or in partnership with, the academic or non-profit sectors, as evidenced by research on the AstraZeneca PLC/Oxford University vaccine, Vaxzevria.
Now an international open-access collaborative initiative that began in 2020 has received new funding to help it discover and develop new candidate compounds for COVID-19 that could be easily produced by any interested manufacturer.
The COVID Moonshot project, a non-profit, open-science consortium of scientists from around the world, aims to identify preclinical molecules by the end of 2021. They will be “simple to manufacture in the form of pills and which will exert an antiviral effect via potent inhibition of the main protease (MPro) of the SARS-CoV-2 virus,” say the partners in the project.
Moonshot has just received £8m ($11m) in funding from the UK-based charitable foundation, the Wellcome Trust, on behalf of the COVID-19 Therapeutics Accelerator (CTA), a philanthropic collaboration that works with the ACT Accelerator.
“Faced with global vaccine inequality and the rapid spread of variants of concern, the need for easily accessible antiviral therapeutics to treat people with COVID-19 is as pressing as ever, especially in low-and middle-income countries,” said Annette von Delft, translational scientist at the University of Oxford and the National Institute for Health Research’s Oxford Biomedical Research Centre.
More than 150 scientists have joined Moonshot to crowdsource ideas for molecular compounds, model them and evaluate them in vitro for anti-SARS-CoV-2 activity, with the aim of finding a “globally affordable, not-for-profit oral treatment for COVID-19 and related viral pandemics,” according to the Moonshot partners.
They include academic and industrial groups such as the UK’s national synchrotron Diamond Light Source, Israel’s Weizmann Institute of Science, the Nuffield Department of Medicine at the University of Oxford (UK), the Memorial Sloan Kettering Cancer Center (US), various drug discovery consultants, and the international Drugs for Neglected Diseases initiative (DNDi), which is “taking the lead in coordinating the Wellcome-funded drive towards the clinic.”
“We want to develop one or more novel pan-coronavirus antiviral molecule for future outbreaks” – Nir London, Weizmann Institute of Science
The project is “based firmly in an open science environment and prioritized simplicity of synthesis of the future drugs, in order to facilitate manufacturing by any interested producer,” said Ben Perry, discovery open innovation leader at DNDi.
All the discovery scientific data and the general learnings of the project will be put in the public domain, the partners say. “Moonshot data is already available online to enable others to freely build on its work – the project has already generated over 50% of known structural information on the main protease, a key protein in SARS-CoV-2. The first clinical trials are expected in 2022.”
“In addition to addressing this current pandemic, which is not showing signs of slowing, we want to develop one or more novel pan-coronavirus antiviral molecule for future outbreaks,” commented Nir London, senior scientist at the Weizmann Institute of Science. “We also want to provide an open platform to accelerate the response time when new pandemics arise.”