CureVac fails in pivotal Covid-19 vaccine trial with 47% efficacy

[vmurthy]

Just jumping in to say that the successes of Pfizer/Moderna/AstraZeneca et al may have primed us to think that vaccines are usually successful but the reality is that these are the exceptions (happy ones!) [0] . I can't find the exact source but most clinical trials don't even move to Phase-3. So failures like CureVac - while sad news indeed - happen :(

[0]https://www.centerwatch.com/articles/12702-new-mit-study-put...

[vladimirralev]

I wonder if it's possible that CureVac had to take some extra risks to be competitive this late in the race. With the Pfeizer/Moderna results already in, may be they aimed to deliver a lower dose vaccine with less side effects that would be more desirable, but that didn't pay off.

[itsdrewmiller]

Vaccines usually are successful (like 80% in phase 3 make it out?) - it’s cancer drugs that ruin the averages since they are very common and never work.

[throwaway4good]

Maybe they should include a baseline vaccine (say pfizer biontech) in their trails instead of just placebo and their own vaccine.

That would show whether the result is due to new variants of the virus or just different efficacy of the new vaccine.

[throwaway4good]

You have broad vaccinations already in some parts of the world, presumably that means that the variants that are still spreading are the ones that are less susceptible to the vaccinations.

[tchalla]

Do we have another baseline that was conducted in a variant rich environment? In this trial, out of the 134 cases - 124 were due to variants from at least 13 types.

[throwaway4good]

Maybe I am naive but what is wrong with this idea?

[tchalla]

> The disappointing efficacy of the shot known as CVnCoV emerged from an interim analysis based on 134 COVID-19 cases in the study with about 40,000 volunteers in Europe and Latin America.

The number of people who had Covid-19 cases seem surprisingly low and there were at least 13 variants amongst 124 cases. The real challenge though lies in the interpretation : is the efficacy due to variants or due to vaccine's inability?

https://www.curevac.com/en/2021/06/16/curevac-provides-updat...

[akiselev]

Doesn't matter as much, now that there are other vaccines on the market. Any new vaccine candidates will be compared against the existing ones as a golden standard and any candidate that doesn't improve on the existing options significantly along some dimension is not likely to get approved.

The desperate scramble to reopen the world led to record development and approval times BY A FREAKING MILE. HN discourages caps but it's hard to overstate just how unprecedented these approvals were. The top 10 list of fastest drug approvals is just a list of chemotherapy drugs and the median time for novel vaccine discovery lies somewhere between decades and centuries. Now that the world is returning to normal, the standards for premarketing approval are too.

[rurban]

This question is answered in the press release. The new variants don't explain this low number alone.

The manufacturer tried to explain that away, that 41% is still extremely good, compared to other vaccines. Nobody followed him there

[refurb]

My counter to that question is - does it matter? This is basically a real world test of the vaccine. If it failed to meet it's endpoint for either reason, it's not a suitable vaccine.

[rich_sasha]

Interesting, if I understand correctly this is an mRNA vaccine too, just doesn’t seem to work that well (though I continue to be amazed at how small the sample sizes are).

What are some of the details that make two vaccines work so differently, even if they use the same underlying technology? Production quality, dosage, slight variation in the active ingredients..?

[Vecr]

The other two have lots of fancy things done to the mRNA itself, including pseudouridine substitutions, 3 and 5 prime untranslated regions, and a poly-a tail. The payload comes from the NIH, and is modified by them as well with proline insertions to stabilize the spike in the prefusion form. All current EUA vaccines in the US (BioNTech, Moderna, Jansen), plus NovaVax (code not delivered to the user in that case) use some form of the NIH payload, as far as I can tell.

Edit: I forgot about the proprietary mRNA delivery systems as well, I don't really know much about those.

[nyokodo]

> I continue to be amazed at how small the sample sizes are

”…an interim analysis based on 134 COVID-19 cases in the study with about 40,000 volunteers in Europe and Latin America.”

The sample size is 40000 is it not? That’s as big as they come.

[makomk]

For all we know it's not actually that much worse than the vaccines currently in use since those were tested before the modern variants were in circulation. (The figures for the effectiveness of the other vaccines aren't entirely comparable - they're not from controlled studies and I don't think they cover one of the latest variants that made up a reasonable proportion of infections in this trial.) I wouldn't be surprised if it's still better than the non-mRNA Johnson & Johnson vaccine too...

[phreeza]

A glance at what could have been, showing us how lucky we really got with >3 working vaccines deployed within a year.

[dharma1]

I wonder if CureVac can come back from this, or are they toast?

[rurban]

My bet is on toast, technically. Gov. money (i.e. taxpayers money) will still keep them afloat though, because they love to keep a 2nd local option.

[thehappypm]

Perhaps they can shift gears and start manufacturing or helping to manufacture the more successful mRNA vaccines, their supply chain might be the saving grace.

[throwaway4good]

I think they raised a lot of money an IPO last year.