Coronavirus Update: J&J Shows Promise Against Omicron, UK Nod For Paxlovid
Plus Comirnaty Touted For Teens
Executive Summary
The FDA authorized Comirnaty as a booster shot for 12- to 15-year-olds, as J&J's vaccine has shown effectiveness as a booster in Omicron-dominant settings. Meanwhile, Pfizer's Paxlovid won approval in the UK, and Novavax submitted the final data for its vaccine to the FDA.
J&J Booster Effective Against COVID-19 Hospitalization
Johnson & Johnson’s COVID-19 vaccine booster has demonstrated 85% effectiveness against COVID-19-related hospitalization according to preliminary data from a study by the South African Medical Research Council.
The Phase IIIb Sisonke trial showed the booster shot reduced the risk of hospitalization from COVID-19 in South African healthcare workers after Omicron became the dominant variant of concern (VOC). During the months studied, the Omicron frequency rose from 82% to 98% of COVID-19 cases in the country, GISAID reported.
Furthermore, a separate analysis of immune response to different vaccine regimens by Beth Israel Deaconess Medical Center (BIDMC) showed a J&J booster jab in people who had initially received Pfizer Inc. and BioNTech SE’s Comirnaty (BNT162b2) caused a 41-fold increase in neutralizing antibody responses after four weeks and a five-fold increase in CD8+ T-cells to Omicron in two weeks.
Since the Omicron VOC has been shown to escape neutralizing antibodies, the observed effectiveness against severe COVID-19 disease and hospitalization could be explained in part by the increase in CD8+ T-cells, the US major claimed. The data are yet to be published in a peer-reviewed journal.
“This adds to our growing body of evidence which shows that the effectiveness of the Johnson & Johnson COVID-19 vaccine remains strong and stable over time, including against circulating variants such as Omicron and Delta,” said R&D head Mathai Mammen.
UK Nod For Pfizer’s COVID-19 Oral Treatment
Paxlovid, Pfizer Inc.’s oral antiviral treatment for COVID-19 that patients can take at home has been cleared for use in the UK. The government and the National Health Service (NHS) will confirm how the drug will be given to patients in due course.
The treatment – a combination of PF-07321332 and ritonavir - is already approved for use under emergency provisions in several other countries, including the US, Israel and South Korea. It is under rolling review in the EU and the European Medicines Agency recently issued advice on the drug’s use to support member states who may decide on its early uptake. (Also see "US FDA Authorizes Pfizer's Paxlovid, In The Nick Of Time" - Scrip, 22 Dec, 2021.)
It is the second such home-use COVID-19 treatment to be approved in the UK, the other being another oral antiviral, Lagevrio (molnupiravir), developed by
Ridgeback Biotherapeutics LP and MSD. (Also see "UK Approval For MSD's COVID-19 Pill Molnupiravir Is A World First" - Pink Sheet, 4 Nov, 2021.)
Supply and availability of Paxlovid remain an issue due to high demand for the product. Pfizer has an agreement with the UK government to supply 2.75 million treatment courses during 2022. This is in addition to the 250,000 treatment courses previously agreed in October 2021. The company said it would begin delivering the first treatment courses in Great Britain in early 2022.
The drug's UK approval by the Medicines and Healthcare products Regulatory Agency was made possible via two different authorization routes - covering Great Britain and Northern Ireland - and comes as the country is dealing with a huge surge in COVID-19 cases driven by the more contagious Omicron variant.
Paxlovid has been awarded a conditional marketing authorization that is valid in Great Britain only. It has also been granted an emergency use authorization covering Northern Ireland. “Both authorizations were made on the basis of the same rigorous evaluation,” the MHRA said.
The treatment is authorized for use in people aged 18 and above who have mild to moderate COVID-19 infection and at least one risk factor for developing severe illness. Such risk factors include obesity, older age (>60 years), diabetes mellitus, or heart disease.
As Paxlovid gets deployed, “we will monitor its effectiveness and safety in the real-world, including any drug interactions, as we do with all medicines,” said Sir Munir Pirmohamed, chair of the Commission on Human Medicines.
The UK has also authorized other COVID-19 therapeutics, specifically monoclonal antibodies - Xevudy (sotrovimab) from GlaxoSmithKline plc and
Vir Biotechnology, Inc., and Ronapreve (casirivimab/imdevimab) from Regeneron Pharmaceuticals, Inc./Roche Holding AG.
Ronapreve Gets Thumbs Up From Swiss Regulator
Swiss regulator Swissmedic has approved Roche Holding AG and Regeneron Pharmaceuticals, Inc.’s antibody cocktail Ronapreve (casirivimab/imdevimab) for the treatment of COVID-19 if oxygen therapy or hospitalization are not needed and there is a high risk of developing severe disease and as a COVID-19 prophylactic in certain cases.
Ronapreve was already available for COVID-19 treatment in Switzerland based on Annex 5 of the COVID-19 Ordinance 3 but it is now the first medicine in the country that can be used to prevent the disease in people who cannot produce an adequate immune response to vaccination due to other diseases or treatments. No data on efficacy against the Omicron variant were submitted for the filing.
Ronapreve was approved by European Commission to treat non-hospitalized COVID-19 patients and for prophylaxis of the disease last month. The antibody cocktail has emergency use authorization from the US Food And Drug Administration but is yet to gain full US approval.
Pfizer/BioNTech Enter Winter With Flurry Of New Comirnaty Nods
The FDA has granted a new emergency use authorization to Pfizer/BioNTech's Comirnaty as a booster shot for adolescents aged 12-15. In addition, amendments to the existing EUA allow a third primary dose for certain immunocompromised children aged 5-11 and, for individuals aged 12 and older, reduce the amount of time to wait for a booster after completing the primary two-shot vaccination series from six months to five.
The flurry of new authorizations again place Comirnaty ahead of the pack in terms of the scope of use for the vaccine, which was already the first to win full FDA approval as well as EUAs allowing use in individuals as young as 5. The vaccine has similar authorization in the European Union, while a study in infants and children aged 6 months to 4 years is ongoing.
That’s on top of the EUA the agency gave Pfizer’s oral antiviral drug combination Paxlovid (nirmatrelvir/ritonavir) on 22 December, just as the more transmissible Omicron variant of SARS-CoV-2 has rapidly become dominant, and antibody treatments like Regeneron’s Ronapreve/REGEN-COV and Eli Lilly & Co. bamlanivimab/etesevimab appear mostly ineffective against it. (Also see "US FDA Authorizes Pfizer's Paxlovid, In The Nick Of Time" - Scrip, 22 Dec, 2021.) Another oral treatment, Merck & Co. Inc./Ridgeback Biotherapeutics LP’s molnupiravir, received an EUA the day after Paxlovid, but that followed a mixed advisory committee vote. (Also see "Divided US FDA AdComm Backs Molnupiravir Authorization But Wants More Studies" - Pink Sheet, 30 Nov, 2021.)
Comirnaty has rapidly achieved mega-blockbuster status, with Pfizer’s third quarter 2021 guidance forecasting full-year sales of $36bn for the vaccine. (Also see "Comirnaty Gives Booster Shot To Pfizer Q3 Sales" - Scrip, 2 Nov, 2021.) Analysts likewise expect double-digit billions in sales for Paxlovid, with Mizuho Securities’ Vamil Divan anticipating the drug combination will generate $24bn in revenue in 2022 and $16bn in 2023.
Meanwhile, Moderna, Inc.’s mRNA-1273 vaccine remains limited to an EUA covering adults. The US Centers for Disease Control and Prevention advised against using J&J’s vaccine. However, more recent data have indicated that the J&J vaccine is effective as a booster against COVID-19 hospitalization due to Omicron.
Novavax Readies EUA Request, But Is It Too Late?
A long-awaited player in the US COVID-19 vaccine market is getting its shot at an EUA as Novavax, Inc. said 31 December that it had submitted its final data package, including the chemistry, manufacturing and controls (CMC) module, for NVX-CoV2373. The company said it would submit a request for an EUA after one month, in accordance with FDA guidance.
While the protein-based vaccine has shown rates of efficacy comparable to those of Pfizer/BioNTech and Moderna’s messenger RNA vaccines, the need to submit CMC data caused multiple delays in its market debut, particularly in the US. Meanwhile, it received a conditional marketing authorization from the European Commission on 20 December, under the brand name Nuvaxovid. (Also see "Nuvaxovid COVID-19 Vaccine Wins EU Approval" - Pink Sheet, 20 Dec, 2021.) Around the same time, it received an emergency use listing from the World Health Organization, while the company also filed for approval in Japan. (Also see "Coronavirus Update: Novavax Vaccine Listed By WHO, Filed In Japan" - Scrip, 20 Dec, 2021.) Novavax and the Serum Institute of India received an emergency use authorization for India on 28 December.
But despite those advances, and the likelihood of an EUA from the FDA, the emergence of the Omicron variant has sparked concerns about whether NVX-CoV2373 can remain competitive, especially if the new strain proves sufficiently capable of evading immunity from the vaccine. Investors had hoped that it could be a genuine rival to the mRNA vaccines given that its high efficacy came with a good safety profile and standard storage requirements. (Also see "Omicron Clouds Novavax’s Delayed COVID-19 Vaccine Debut" - Scrip, 3 Dec, 2021.) Indeed, Novavax had already signaled that it anticipated that NVX-CoV2373 would mostly play a niche role as a booster shot in markets outside of the US. (Also see "Novavax Pins COVID-19 Hopes On Ex-US, Booster Markets" - Scrip, 6 Aug, 2021.)
However, on 22 December, Novavax said that the two-dose primary vaccination series of NVX-CoV2373 showed cross-reactive immune responses against Omicron and other variants, while a third booster shot resulted in increased immune responses comparable to or exceeding the levels seen in Phase III studies, with IgG titers increasing from more than fivefold to more than ninefold and ACE2-inhibition titers increasing from sixfold to nearly twentyfold.