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"is substantially different" is correct and usable in written English.
You can use it to describe how two things are significantly different from one another. For example, "The climate in Mexico is substantially different from that in Canada."
Exact(60)
However, in the crisis period, the difference in spreads is substantially different.
But for some, the reality is substantially different.
That operating system is substantially different from Apple's.
Now, he said, "the profile of the renters is substantially different".
And it's luck that animates his novel, which is substantially different from the film.
The Hypnotic-Universal contest, the Million Dollar Film Festival, is substantially different.
The sound that comes off Dormeshia Sumbry-Edwards's shoes is substantially different from Dorrance's.
The paper is substantially different to its London namesake and is run independently.
Overall the real picture is substantially different than the one Reagan paints for his audiences.
First, the baseline probability of force in each of the data sets is substantially different.
The construction of low-speed synchronous generators is substantially different from that of high-speed units.
More suggestions(15)
is substantially divergent
is markedly different
is greatly different
is vastly different
is very significantly different
is substantially varied
is significantly different
is dramatically different
is slightly different
is marginally different
is substantially due
is basically different
is widely different
is quite different
is mainly different
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Since I tried Ludwig back in 2017, I have been constantly using it in both editing and translation. Ever since, I suggest it to my translators at ProSciEditing.

Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com