Global regulators agree on key principles on adapting vaccines to tackle virus variants
On 30 June, regulators from around the world discussed emerging evidence to support adaptation of COVID-19 vaccines as the SARS-COV-2 virus continues to evolve during a workshop co-chaired by the EMA and the US FDA under the umbrella of the International Coalition of Medicines Regulatory Authorities (ICMRA). The meeting focused on identifying key principles to support the adaption of COVID-19 vaccines to better match Omicron variants of concern, and on ensuring global regulatory alignment.
- ICMRA members and WHO agreed that authorised COVID-19 vaccines continue to offer protection against severe disease, hospitalisation and death and encouraged their use, where available, both as primary series and as booster doses.
- Global regulators also acknowledged that the continuous evolution of SARS-CoV-2 reduces the protection offered by the approved vaccines against infection and mild disease.
- Although the Omicron BA.4 and BA.5 subvariants seem to be taking over in many parts of the world, experience has shown that new variants may emerge rapidly and replace the currently circulating ones after short-lived waves.
- Preliminary data indicate that adapted mRNA vaccines, which incorporate an Omicron variant strain, can increase and extend protection, when used as a booster.
- Additionally, according to emerging data, a bivalent mRNA vaccine targeting two strains of SARS-CoV-2, one of which should be an Omicron strain, may provide some advantages in widening the immune response. Bivalent vaccines could be considered initially for use as boosters. Their use for primary vaccination might be supported in the future when further data become available.
- Vaccines which include other variants, for example the beta variant, might also be considered for use as boosters if clinical trial data demonstrate an adequate level of neutralisation against Omicron and other variants of concern.
Status of administered COVID-19 doses across the globe
As of 30 June, 66.4% of the world population has received at least one dose of COVID-19 vaccine. 12.07 billion doses have been administered globally and 5.35 million are now administered each day.
Only 17.4% of the people in low-income countries have received at least one dose.
COVID-19 vaccines approved and in clinical trials globally
This site (link below) provides some very basic but useful information on the global progress with clinical trials for vaccines for COVID-19. You can also view information on vaccine approvals by country.
As of 29 June, the situation is as follows:
- No of vaccines in Phase I trials = 53
- No of vaccines in Phase II trials = 72
- No of vaccines in Phase III trials = 80
- No of approved vaccines = 39
More information on the regulatory status of vaccines or medicines is available here.
EFPIA and Vaccines Europe express disappointment at decision taken by the World Trade Organisation at the Ministerial Conference (MC12) to endorse a TRIPS waiver for COVID-19 vaccines
Speaking about the waiver, EFPIA Director General, Nathalie Moll said. “The decision is a serious retrograde step in our collective ability to tackle the COVID-19 pandemic and future global health threats. The last two years have underlined that the only effective response to pandemics is grounded in research, development and innovation. That ability to respond is built on having a solid IP framework.”
The decision at MC12 sends a dangerous signal not only to the pharmaceutical industry but to all innovative sectors. Dismantling the very framework that has brought solutions to tackle COVID-19 and facilitated the unprecedented number of partnerships, voluntary licensing, and knowledge-sharing taking place during this pandemic in record breaking time, can have ripple effects for the future.
PRAC finds no link between mRNA COVID-19 vaccines and absence of menstruation
The PRAC concluded that there is insufficient evidence to establish a causal association between the COVID-19 vaccines Comirnaty and Spikevax and cases of absence of menstruation (amenorrhoea).
Absence of menstruation may be defined as no bleeding for a period of 90 days or more.
PRAC assessed all the available data, including findings from the literature and cases of amenorrhea reported to EudraVigilance following the administration of Comirnaty and Spikevax.
Overall, the PRAC considered that the available data does not support causal association and an update of the product information for either vaccine.
The committee will continue to carefully monitor this issue and has requested the marketing authorisation holders to include it in the next periodic safety update reports (PSURs) for Comirnaty and Spikevax.
Source: European Medicines Agency
Potential delay for Novavax jab EUA in the US
Earlier this week, the Novavax shot appeared close to its long-awaited approval, as an independent FDA advisory panel voted 21-0 to recommend it for authorisation. However, now the FDA says that it will have to sign off on changes Novavax recently made to its manufacturing process for the vaccine. The company informed the agency of these changes last Friday, four days before the agency’s expert panel reviewed the application.
On Thursday, Novavax confirmed the June 3 submission, saying that it has shared relevant information with the FDA since applying for emergency use authorisation back in January.
According to a company spokesman, “the data is a part of the standard process improvements that have been made since submission.”
Draft texts on WTO response to pandemic, IP response sent to ministers for decision
Negotiators in Geneva finalised their work on two draft texts setting out a WTO response to the COVID-19 pandemic, including an intellectual property (IP) response. The two texts will now be sent to trade ministers attending the organization’s 12th Ministerial Conference (MC12) for review and possible approval.
The draft text on the WTO response to the pandemic sets out a series of trade-related pledges and objectives in order to support increased resilience to COVID-19 and future pandemics. These include general as well as specific provisions relating to trade facilitation, regulatory cooperation, intellectual property, services, food security and aspects of future work.
Trials of new Moderna Covid vaccine raise hopes of once-a-year booster
An updated version of Moderna’s Covid vaccine (the first “bivalent” formulation to combine protection against Omicron and the original strain of coronavirus) produces an eightfold increase in antibody levels against the Omicron variant, according to early trial results, raising hopes for a once-a-year booster to protect against the disease. It is the company’s leading candidate for upcoming autumn booster programmes.
Dr Paul Burton, Moderna’s chief medical officer, said the new vaccine raised antibody levels to such a degree that one booster a year could be enough, unless a substantially different variant calls for the vaccine to be redesigned again.
Source: The Guardian
EMA press briefing on COVID-19 and monkeypox
Here is a link to the briefing of 2 June.
Swissmedic vigilance news – successful re-exposure to COVID-19 mRNA vaccination at a reduced dosage in a patient with clinically suspected pericarditis/myocarditis
In the Swissmedic Vigilance-News Edition 28 of May 2022, is a report of a successful re-exposure to COVID-19 mRNA vaccination at a reduced dosage of the vaccine tozinameran (Comirnaty®) in a 24 year old male patient with clinically suspected pericarditis/myocarditis after a first dose of COVID-19 vaccine elasomeran (Spikevax®).
Three shots of low-dose vaccine generates ‘strong immune response’ in kids under 5, says Pfizer
Pfizer and BioNTech said they will ask the US FDA to authorise a three-shot regimen of their Covid-19 vaccine for children under five years of age, citing promising clinical trial results, offering hope for parents wanting to vaccinate their young children after months of delays following disappointing trial results for two doses.
Three doses of Pfizer and BioNTech’s Covid-19 vaccine produced a “strong immune response” in children under five, according to results from a clinical trial, the companies announced today.
The trial, which has not yet been peer reviewed or published and was conducted at a time when omicron was the predominant variant, assessed a third dose in 1,678 children after trial results found two doses insufficient and regulators requested more information.
WHO and MPP announce agreement with NIH for COVID-19 health technologies
On 12 May, WHO’s COVID-19 Technology Access Pool (C-TAP) and the Medicines Patent Pool (MPP) finalised a licensing agreement with the United States National Institutes of Health (NIH) for the development of several innovative therapeutics, early-stage vaccines and diagnostic tools for COVID-19.
The licences, which are transparent, global and non-exclusive, will allow manufacturers from around the world to work with MPP and C-TAP to make these technologies accessible to people living in low- and middle-income countries and help put an end to the pandemic.
The 11 COVID-19 technologies offered under two licences include the stabilised spike protein used in currently available COVID-19 vaccines, research tools for vaccine, therapeutic and diagnostic development as well as early-stage vaccine candidates and diagnostics. The full list of the NIH COVID-19 technologies covered in the agreement is available here.
Source: Medicines Patent Pool
14.9 million excess deaths associated with the COVID-19 pandemic in 2020 and 2021
According to new estimates released from the World Health Organization (WHO) on 5 May, the full death toll associated directly or indirectly with the COVID-19 pandemic (described as “excess mortality”) between 1 January 2020 and 31 December 2021 was approximately 14.9 million (range 13.3 million to 16.6 million).
Excess mortality is calculated as the difference between the number of deaths that have occurred and the number that would be expected in the absence of the pandemic based on data from earlier years.
Excess mortality includes deaths associated with COVID-19 directly (due to the disease) or indirectly (due to the pandemic’s impact on health systems and society). Deaths linked indirectly to COVID-19 are attributable to other health conditions for which people were unable to access prevention and treatment because health systems were overburdened by the pandemic. The estimated number of excess deaths can be influenced also by deaths averted during the pandemic due to lower risks of certain events, like motor-vehicle accidents or occupational injuries.
Most of the excess deaths (84%) are concentrated in South-East Asia, Europe, and the Americas. Some 68% of excess deaths are concentrated in just 10 countries globally. Middle-income countries account for 81% of the 14.9 million excess deaths (53% in lower-middle-income countries and 28% in upper-middle-income countries) over the 24-month period, with high-income and low-income countries each accounting for 15% and 4%, respectively.
The estimates for a 24-month period (2020 and 2021) include a breakdown of excess mortality by age and sex. They confirm that the global death toll was higher for men than for women (57% male, 43% female) and higher among older adults. The absolute count of the excess deaths is affected by the population size. The number of excess deaths per 100,000 gives a more objective picture of the pandemic than reported COVID-19 mortality data.
ICER final evidence report and policy recommendations on outpatient treatments for COVID-19
On 10 May, the Institute for Clinical and Economic Review (ICER) released a Final Evidence Report assessing the comparative clinical effectiveness and value of the following outpatient treatments for COVID-19:
- molnupiravir (Merck)
- PF-07321332/ritonavir (Paxlovid™, Pfizer)
- fluvoxamine (Investigator initiated)
Information on monoclonal antibody treatments sotrovimab and REGEN-COV2 is included in supplemental documents to the report due to the fact that at the time of this final report, these treatments no longer had active emergency use authorisation (EUA) from the Food and Drug Administration (FDA) for use in any U.S. region.
Voting on Clinical Effectiveness and Contextual Considerations
A majority (11-2) found current evidence is not adequate to demonstrate a net health benefit when molnupiravir is compared to symptomatic care alone.
All panelists (13-0) found that current evidence is adequate to demonstrate a net health benefit when Paxlovid is compared to symptomatic care alone.
A slight majority (7-6) found that current evidence is adequate to demonstrate a net health benefit when fluvoxamine is compared to symptomatic care alone.
During their deliberations, panel members also weighed the therapies’ other potential benefits, disadvantages, and contextual considerations. Discussion highlighted the following potential benefits of effective outpatient treatments for COVID-19 beyond those of health improvement for individual patients:
Effective outpatient treatments for mild-moderate COVID-19
- may help reduce population spread of COVID-19.
- may reduce the number of hospitalised patients enough to increase capacity to treat non-COVID-19-related conditions.
- will help address the disparate burden of the pandemic in disadvantaged communities.
- may help provide psychological reassurance allowing for broader opening of schools and workplaces.
Molnupiravir cannot be used in people who are attempting to conceive or who are pregnant.
Paxlovid has many drug-drug interactions that may limit the number of patients who can use it.
Fluvoxamine affects a different phase in COVID-19 pathophysiology and therefore it may be possible to combine its use with other agents.
You can view the report at a glance here.
Chair says WTO meeting on COVID vaccine rights waiver went very well
The first World Trade Organization meeting to discuss a draft agreement to temporarily waive intellectual property rights for COVID-19 vaccines went “very well”, its chair said on Friday, although some members voiced reservations.
The WTO’s 164 members on Friday discussed the “outcome document” that stems from months of negotiations between the main parties – the United States, the European Union, India and South Africa – in an effort to break an 18-month deadlock over the issue.
Ambassador Lansana Gberie from Sierra Leone, who chairs the council tasked with finding an agreement on the waiver, told Reuters after the closed-door meeting that the meeting went “Very well since no member rejected the outcome as completely unacceptable. Most said this could be developed into a negotiating text and that’s the trajectory we have to follow.”
The waiver idea, proposed by India and South Africa in October 2020, is supported by the majority of members of the global trade body, but some wealthy countries including Britain and Switzerland have in the past raised objections on grounds that it could harm pharmaceutical research.
The new draft deal, which has unresolved areas, must pass by consensus and any member of the organisation has the right to a veto.
EMA Press Briefing on COVID-19 related activities
Here is a link to the EMA press briefing of 5th May.
FDA Limits Use of Janssen COVID-19 Vaccine to Certain Individuals
After conducting an updated analysis, evaluation and investigation of reported cases, the FDA has determined that the risk of thrombosis with thrombocytopenia syndrome (TTS), a syndrome of rare and potentially life-threatening blood clots in combination with low levels of blood platelets with onset of symptoms approximately one to two weeks following administration of the Janssen COVID-19 Vaccine, warrants limiting the authorized use of the vaccine.
The FDA has therefore limited the authorized use of the Janssen COVID-19 Vaccine to individuals 18 years of age and older for whom other authorized or approved COVID-19 vaccines are not accessible or clinically appropriate, and to individuals 18 years of age and older who elect to receive the Janssen COVID-19 Vaccine because they would otherwise not receive a COVID-19 vaccine.
Study finds that cognitive impairment from severe COVID-19 is equivalent to 20 years of ageing.
Cognitive impairment as a result of severe COVID-19 is similar to that sustained between 50 and 70 years of age and is the equivalent to losing 10 IQ points, say a team of scientists from the University of Cambridge and Imperial College London.
There is growing evidence that COVID-19 can cause lasting cognitive and mental health problems, with recovered patients reporting symptoms including fatigue, ‘brain fog’, problems recalling words, sleep disturbances, anxiety and even post-traumatic stress disorder (PTSD) months after infection.
While even mild cases can lead to persistent cognitive symptoms, between a third and three-quarters of hospitalised patients report still suffering cognitive symptoms three to six months later.
To explore this link in greater detail, researchers analysed data from 46 individuals who received in-hospital care, on the ward or intensive care unit, for COVID-19 at Addenbrooke’s Hospital, Cambridge. The individuals underwent detailed computerised cognitive tests an average of six months after their acute illness. Their data were compared against matched controls.
COVID-19 survivors were less accurate and with slower response times than the matched control population, with deficits still detectable when the patients were following up six months later. The effects were strongest for those who required mechanical ventilation. By comparing the patients to 66,008 members of the general public, the researchers estimate that the magnitude of cognitive loss is similar on average to that sustained with 20 years ageing, between 50 and 70 years of age, and that this is equivalent to losing 10 IQ points.
The findings are published in the journal eClinicalMedicine.
Professor David Menon from the Division of Anaesthesia at the University of Cambridge, the study’s senior author, said “We followed some patients up as late as ten months after their acute infection, so were able to see a very slow improvement. While this was not statistically significant, it is at least heading in the right direction, but it is very possible that some of these individuals will never fully recover.”
Source: Cambridge university website