J&J vaccine nears US approval
The FDA is likely to approve a third COVID-19 vaccine within the next week with the added bonus that it can be administered by a single injection.
The imminent availability of Johnson & Johnson’s Ad26.COV2.S, which will be discussed by experts at an advisory committee meeting on Friday, should therefore help to accelerate the US vaccination programme, and those in other countries once approved by other global regulators.
The question is how vaccines like Ad26.COV2.S, which the FDA has confirmed shows overall efficacy of 66% at preventing COVID-19 infection, are perceived in the long-term against the more efficacious mRNA vaccines.
Like AstraZeneca’s AZD1222, the effectiveness of Ad26.COV2.S at preventing severe disease and hospitalisation is higher, even against more severe variants of COVID-19. In the near term at least this will likely be sufficient to allow these vaccines play a key role in bringing the pandemic under control.
Real world vaccine data impresses
On this front, encouragement is provided by early results showing that both AZD1222 and BioNTech’s and Pfizer’s mRNA vaccine Comirnaty are performing as well in a real world-setting as they did in clinical studies. This includes new data from a large real-world analysis of over a million participants from Israel, half of whom had received vaccination with Comirnaty, which was published this week in the New England Journal of Medicine (NEJM)
These results show that Comirnaty prevented 94% of symptomatic COVID-19 seven days after a second dose and 92% of severe cases. Comirnaty was also shown to prevent 66% of symptomatic COVID-19 and 80% of severe disease three-to-four weeks after one dose.
Late last week, data from a UK study showed that one dose of Comirnaty or AstraZeneca’s vaccine AZD1222 reduced COVID-19 hospitalisation by 85% and 94%, respectively. More UK data from a separate analysis showed that a single dose of Comirnaty was shown to be 72% effective at preventing symptomatic and asymptomatic COVID-19, rising to 86% seven days after a second dose.
mRNA developers gear up to tackle variants
One argument is that use of vaccines which prevent a high proportion of severe cases and hospitalisations but have lower overall efficacy will allow COVID-19 to remain in higher circulation and possibly give rise to the emergence of new variants. In a worst case scenario, this could allow the virus to mutate sufficiently to evade immunisation altogether.
That said, fully to what extent existing or new COVID-19 variants shape future vaccine development remains unclear at this point but looks certain to be one of the key factors (in tandem with how frequently vaccination is required) that will determine the size of the future COVID19 vaccine market.
By comparison, near term vaccine revenues are guaranteed to be significant with Moderna announcing on Thursday that it expects to book revenues in excess of $18 billion this year.
This week the FDA issued guidance for the development of new versions of existing vaccines or boosters designed to combat variants, confirming that new large scale clinical studies will not be necessary. On Thursday the EMA provided similar guidance, indicating that small bridging studies will be required for modified vaccines developed against novel variants.
Tweaking existing vaccines in such a way may favour those which use mRNA technology, experts suggest, which could cement this approach as the gold standard. On cue, Moderna announced on Wednesday that it has manufactured the initial batch of an updated version of its COVID-19 vaccine designed to better protect against the B.1.351 variant of SARS-CoV-2 first identified in South Africa. Doses of this new candidate have been shipped to the US National Institute of Allergy and Infectious Diseases for testing in a Phase I clinical trial pending a green light from the FDA. Booster shots could also require smaller doses meaning that more vaccine can be produced over time, Moderna believes.
On Thursday BioNTech and Pfizer announced that they have begun to evaluate the safety and immunogenicity of a third dose of Comirnaty to understand its effect on immunity against COVID-19 caused by circulating and potential newly emerging SARS-CoV-2 variants. Pfizer says there is some real-world evidence to suggest that people previously infected with COVID-19 experience a greater immune response when vaccinated with Comirnaty. Use of a three-dose regimen may replicate this effect.
Merck acquires Pandion
Merck & Co. will pay $1.85 billion to acquire Pandion Therapeutics, taking a punt on a novel approach to treating autoimmune diseases by using an engineered IL-2 therapy to target and stimulate an increase in regulatory T-cells (or Tregs).
A handful of other companies are investigating a similar approach, although recently announced top-line Phase I data for lead asset PT101 suggests Pandion’s drug may be particularly effective at increasing Tregs but not natural killer (NK) cells or pro-inflammatory conventional T cells (Tconv) at any dose level. Analysis here
Pandion plans to initiate a Phase 1b/2a clinical trial for PT101 in patients with ulcerative colitis in mid-2021 and a Phase 2 clinical trial in patients with systemic lupus erythematosus in the second half of the year.
Will Xeljanz safety concerns cast doubt on all JAKs?
Our new survey of rheumatologists suggests that final data from the ORAL Surveillance outcomes study (assessing Pfizer’s JAK inhibitor Xeljanz versus Humira) could have a bigger impact on the US market than Europe. These outcomes data are concerning with recently announced top-line results showing an increased serious toxicity risk – major cardiovascular events and malignancies – with both the 5-mg and 10-mg versions of Xeljanz.
US rheumatologists we surveyed said that on average they treat around 12% of their RA patients with Xeljanz. Assuming no other major toxicity risks are cited when full data from ORAL Surveillance are presented, they suggest additional label warnings for Xeljanz will pull its share down by around 3 percentage points to 9%.
On the one hand this indicates that sales of Xeljanz are unlikely to fall off a cliff. Our survey also reveals, for example, that despite acknowledgement Xeljanz’s long-term safety profile raises some concerns, the overall risk benefit of using Pfizer's drug leans heavily on its compelling efficacy, oral dosing and is supported by rheumatologists having accumulated nearly a decade's worth of experience using the drug.
More intriguing, however, is the suggestion that any new concerns about Xeljanz's safety profile could have a broader impact on overall use of JAK inhibitors in the US market versus Europe. Feedback from our survey consistently shows that a higher proportion of US rheumatologists are more likely to be concerned about broader JAK use than their European counterparts as a result of new safety data specific to Xeljanz.
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