Moderna’s highly-anticipated COVID-19 vaccine candidate has shown promise in a key early trial, producing antibodies in all participants tested.

The interim analysis of the phase 1 study of the candidate, mRNA-1273, evaluated a two-dose vaccination schedule of the shot given 28 days apart across three dosages – 25, 100, 250 µg – in 45 healthy adults aged 18-55 years. The initial results from participants who received both doses showed mRNA-1273 produced rapid and strong immune responses against SARS-CoV-2, the virus which causes COVID-19.

Despite producing a promising immune response in all patients, the vaccine also caused side effects, including mild to moderate fatigue, chills, headache and muscle pain.
In addition to those milder side effects, 40% of participants in the middle-dose group experienced a fever after the second vaccinations, with three of the 14 patients in the high-dose group experiencing severe side effects.

However, the high dose is no longer being used in the next, large-scale trials, with Moderna deciding that the prime dose level of 100µg will be used in later studies based on these early results.

Following two doses with the vaccine, neutralising antibodies’ levels among participants were similar to those seen in individuals who had tested positive and recovered from COVID-19. Although high levels of neutralising antibodies are not definitive proof that a vaccine is effective, they are still considered an important indicator of efficacy in early clinical trials.

The presence of such a promising immune response could signal that Moderna’s vaccine candidate will have the ability to protect against the virus later down the development line. Moderna will continue to evaluate the durability of the immune response in the phase 1 participants, who will be followed for one year after the second vaccination, with scheduled blood collections throughout that period.

The company has completed enrolment of two cohorts – healthy adults aged 18-55 years and older adults aged 55 years and above – in its phase 2 study of the vaccine. Study protocol for a phase 3 study has been also reviewed by the US Food and Drug Administration (FDA) and aligns with the agency’s recent guidance on clinical trial design for COVID-19 vaccine studies.

In new data released detailing the efficacy of Gilead’s investigational antiviral remdesivir, the drug reduced the risk of death by 62% in severely ill COVID-19 patients.

The additional remdesivir data, presented at the Virtual COVID-19 Conference last week, includes new comparative analysis from the phase 3 SIMPLE-Severe trial and a real-world retrospective cohort of patients with severe COVID-19. In this analysis, remdesivir demonstrated an improvement in clinical recovery and an impressive 62% reduction in the risk of death when compared with standard of care.

Analyses from separate subgroups investigated in the trial also included an evaluation of safety and efficacy of remdesivir across different racial and ethnic patient subgroups. Results from these analyses found that ‘traditionally marginalised racial or ethnic groups’ treated with remdesivir experienced similar outcomes to the overall patient population in the study.

Gilead also revealed new analyses from its compassionate use programme, which demonstrated that 83% of paediatric patients and 92% of pregnant and postpartum women with a broad spectrum of disease severity recovered by day 28 of treatment.

Some analysts have taken issue with the validity of the data, given that the source of the analysis is not from a randomised, placebo-controlled clinical trial, but rather compares clinical trial data to non-clinical trial data.

However, given the urgency of the pandemic, drug developers are releasing any data which may show a benefit against the disease as the need for treatments grows increasingly critical. This fact has been acknowledged by Gilead – its chief medical officer Merdad Parsey commented on the release of this data last week: “To address the urgency of the continuing pandemic, we are sharing data with the research community as quickly as possible with the goal of providing transparent and timely updates on new developments with remdesivir,” he said in a statement.

“The data presented at the Virtual COVID-19 Conference shed additional light on the use of remdesivir in specific patient populations, including those that may be susceptible to higher rates of COVID-19 infection, as well as others that are particularly vulnerable, including children and pregnant and postpartum women,” he added.

Former US Food and Drug Administration (FDA) commissioner Scott Gottlieb also said that rigorous confirmation is needed to further support the data, tweeting that ‘this is very encouraging but needs to be confirmed in a prospective trial’.

‘It appears to be a retrospective analysis of the phase 3 data using historical matched controls, suggesting a survival benefit in severe COVID-19 patients,’ he added.

After global deaths caused by COVID-19 topped over half a million, the World Health Organization (WHO) held a virtual summit last week tracking the progress of COVID-19 research and development.

Researchers, developers and funders from across the globe attended the two half-day virtual summit on 1 and 2 July to examine the progress made so far in the development of effective health tools that can be used to improve the global response to the coronavirus pandemic.
As part of that effort, the group reviewed the most recent data from the WHO Solidarity Trial of four potential COVID-19 treatment options, as well as other completed and ongoing trials evaluating other treatments. That included detailed data on hydroxychloroquine, lopinavir/ritonavir, remdesivir and dexamethasone. The consensus reached by the group is that overall, more trials are needed to test antivirals, immunomodulatory drugs, anti-thrombotic and combination therapies at different stages of disease progression.

The WHO also took the decision to discontinue the Solidarity Trial’s hydroxychloroquine and lopinavir/ritonavir arms following a review of evidence obtained at the interim analysis.
These results showed that neither hydroxychloroquine nor lopinavir/ritonavir significantly reduced the mortality rate of hospitalised COVID-19 patients when compared to standard of care. There were also some associated safety signals in clinical laboratory findings of the add-on Discovery trial associated with each drug.

On top of the discussions surrounding the research into potential COVID-19 therapies, the group also analysed 15 vaccine trial designs from a number of developers, as well as the criteria for conducting robust trials to assess safety and efficacy of vaccine candidates.
That included taking a look at the use of global, multi-country, adaptive trial design with a common data safety monitoring board and clear criteria that would allow candidates to advance seamlessly through various stages of trials.

The group also identified that most internationally funded research projects have tended to favour high-income countries, with few projects funded in low- and middle-income countries so far.
They noted that this disparity highlights the ongoing need for the WHO’s ACT-Accelerator Initiative, which aims to accelerate the development and equal access of COVID-19 therapeutics and health tools.

“We must act in the interests of global solidarity and our shared humanity. We have a shared responsibility to ensure that all people have access to the tools to protect themselves, especially those who are most at risk,” said WHO director-general Tedros Adhanom Ghebreyesus at a media briefing.

The US Food and Drug Administration (FDA) has awarded fast-track designations to two of Pfizer and BioNTech’s investigational COVID-19 vaccine candidates.

The two candidates, BNT162b1 and BNT162b2, are the most advanced investigational vaccines in Pfizer/BioNTech’s BNT162 mRNA-based vaccine programme, and are currently being evaluated in ongoing phase 1/2 clinical studies.

The FDA fast-track status was granted based on preliminary data from phase 1/2 studies that are currently ongoing in the US and Germany, as well as findings from animal immunogenicity studies. Initial clinical data for BNT162b1 demonstrated that the experimental vaccine was both well tolerated and generated dose-dependent immunogenicity.

The preliminary clinical data evaluated 24 subjects who received two injections of 10µg and 30µg, and nine subjects who received two doses of placebo control, 21 days apart. In addition to the participants who received two doses, another group received a single dose of 100µg.

The BNT162 programme is evaluating at least four experimental vaccines, each of which represents a unique combination of messenger RNA (mRNA) format and target antigen. Both BNT162b1 and BNT162b2 are nucleoside modified RNAs, formulated in lipid nanoparticles. BNT162b1 encodes an optimised SARS-CoV-2 receptor-binding domain (RBD) antigen. BNT162b2 encodes an optimised SARS-CoV-2 full-length spike protein antigen.

An FDA fast-track designation expedites the review of new drugs and vaccines that are intended to treat or prevent serious conditions and have the potential to address an unmet medical need. According to Pfizer, it expects to start a phase 2b/3 trial as soon as later this month, and is anticipating enrolling up to 30,000 subjects in the large-scale study.

Subject to efficacy and regulatory approval, Pfizer and BioNTech expect to manufacture up to 100 million doses of the successful vaccine candidate by the end of 2020 and potentially more than 1.2 billion doses by the end of 2021.

Pfizer and BioNTech were selected to join the US Department of Health & Human Services’ Operation Warp Speed in June, which aims to deliver 300 million doses of a safe and effective COVID-19 vaccine by January 2021, as part of a broader strategy to accelerate the development, manufacturing and distribution of COVID-19 vaccines, therapeutics and diagnostics.