Regdanvimab

EMA’s Emergency Task Force (ETF) has cautioned that monoclonal antibodies currently authorised for COVID-19 are unlikely to be effective against emerging strains of SARS-CoV-2. These monoclonal antibodies are designed to neutralise the virus by binding to the spike protein on its surface. However, emerging strains have mutations in this protein which can reduce the ability of the antibodies to bind to them. Recent laboratory studies show that monoclonal antibodies targeting the spike protein are poorly effective at neutralising Omicron strains BA.4.6, BA.2.75.2 and XBB. The data also show that these monoclonal antibodies do not significantly neutralise BQ.1 and BQ.1.1, which are expected to become the dominant strains in the EU in the coming weeks. Although it is not yet known to what extent the reduced neutralising activity translates into reduced benefits for patients, healthcare professionals will need to consider alternative treatments, especially if subvariants such as BQ.1 and BQ.1.1 become prevalent. Antiviral treatments such as Paxlovid (nirmatrelvir / ritonavir) and Veklury (remdesivir), which have different mechanisms of action, are expected to retain their activity against the emerging strains. These treatments are approved in the EU for patients with COVID-19 who do not require supplemental oxygen and are at increased risk of their disease progressing to severe COVID-19. The ETF therefore encourages EU Member States to ensure that healthcare professionals have access to these antiviral treatments for patients at increased risk of severe COVID-19. The ETF, along with the European Centre for Disease Control and Prevention (ECDC), will continue to monitor the epidemiological situation in the EU. The ETF will also consider recommending an update to the product information for individual monoclonal antibodies. More about the medicines A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen). Four authorised monoclonal antibodies attach to the spike protein of SARS-CoV-2 and by doing so prevent the virus from being able to enter the body’s cells. These are Evusheld (tixagevimab / cilgavimab), Regkirona (regdanvimab), Ronapreve (casirivimab / imdevimab) and Xevudy (sotrovimab). EMA has issued advice on the use of a fifth product (bamlanivimab / etesevimab) under Article 5(3) of Regulation 726/2004. These monoclonal antibodies are used for treating COVID-19 in patients at increased risk of their COVID-19 disease becoming severe and who do not require supplemental oxygen. Some monoclonal antibodies are also approved for preventing COVID-19. The ETF statement does not refer to RoActemra, another monoclonal antibody, which does not target the virus but acts as a modulator of the immune response and is used with a corticosteroid medicine in patients who require extra oxygen or mechanical ventilation (breathing assisted by a machine). More information about other medicines authorised for treating COVID-19, including Paxlovid and Veklury, is available on EMA’s COVID-19 treatments page.

With the rise of Omicron last year, there have been a few subvariants introduced — especially BA.2 and BA.5 in the US. Now, there’s another one but it’s mostly confined to India. BA.2.75, first discovered in late May/early June in India, is yet another subvariant of Omicron. Primarily dominant in India, samples have been found in Nepal, Japan, Australia, and other countries such as New Zealand and the US in low amounts. Nicknamed “Centaurus,” the variant has concerned a few scientists. Tom Peacock, a virologist at Imperial College London, told Science that the new variant does not look like a new Omicron variant — rather an entirely new variant in part to some major genomic changes. “This looks exactly like Alpha did, or Gamma or Beta,” Peacock added. Former Harvard Medical School professor William Haseltine wrote in an article at Forbes that an initial study looking at BA.2.75 indicated that only three treatments could be effective against the new subvariant if it becomes dominant: Celltrion’s regdanvimab, GSK and Vir’s sotrovimab, and tixagevimab, half of AstraZeneca’s Evusheld. A study from the New England Journal of Medicine published yesterday noted that the dominant Omicron subvariant right now is less susceptible to Evusheld. However, some people think that the subvariant will not catch on as the dominant variant of expression on the global/Western stage. As Scripps Research Translational Institute founder and director Eric Topol tweeted out: South Africa’s CERI (Center for Epidemic Response and Innovation) director Tulio de Oliveira concurred. BA.5 is currently the dominant variant in the US, making up more than 50% of all Covid-19 cases. BA.2 used to be more dominant in early 2022, as one of the treatments for it, GSK and Vir’s sotrovimab, was pulled from the market in April due to the lost efficacy. While the pair hasn’t given up on sotrovimab — looking to file for full FDA approval this year — several therapies in the US armamentarium in the fight against Covid-19 have been rendered less effective against BA.2. Shionogi’s Covid-19 oral treatment did not win approval for emergency use. A report from Reuters indicated that Shionogi’s treatment failed to get the nod from a health ministry panel — leading the biotech’s share price to initially fall 15% before slowing coming back up. The panel voted to wait for more data from ongoing clinical trials and continue discussions on the drug, according to Reuters . The report also noted that the Japanese biotech was looking to have the third oral pill approved in the country to treat Covid-19 — behind Pfizer’s Paxlovid and Merck’s Lagevrio. The biotech announced a year ago that it was starting clinical trials, putting itself months behind the two Big Pharma competitors. The report also noted that Shionogi had signed an agreement to sell close to a million doses to the Japanese government, pending the drug’s approval. This delay was also not the first delay for the biotech — as Reuters noted, “Last month a health ministry panel postponed a ruling on the drug because of uncertainty over its effectiveness, as well as animal studies showing it could pose a risk to pregnancies.”