I’m coming to the same conclusion: All reports so far come from users with RME interface and Ryzen systems.
@glueman , unfortunately, fixing this issue depends on getting hold of a system where we can reproduce the issue and debug it. We were not able to reproduce this inhouse so far 
. But the possible Ryzen link is a promising approach.
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Ryzen 5 5600X on MSI MPG B550 Gaming Plus
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That happened to me too, when i started on this system it was rock solid, but than I did multiple updates and installed some third party plugins and the trouble started to become a big problem
Windows 11, Ryzen 9 3900X on MSI B550-A PRO (drivers, bios and windows up to date). Fireface is connected directly to one Mainboard USB-Input, no USB hub in between.
Thanks for still keeping an eye on this issue @Chriss !
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I re-read your previous messages and noticed that you only have issues with Cubase using ASIO, not with other DAWs. I missed that important detail earlier, sorry!
Looking at your motherboard manual, you have several USB ports: 4x USB 2.0 Type-A, 2x USB 3.2 gen 1 Type A(previously 3.0), 1x USB 3.2 Gen 2 Type-A and 1x USB 3.2 Gen 2 Type-C.
According to the manual, all the USB 3.2 ports are connected to the CPU, while only the USB 2.0 ports are connected to the B550 chipset. Ideally, I would connect the RME to one of the CPU ports, but have you tried using the USB 2.0 ports?
You might also consider trying an inexpensive USB 2.0/3.0 powered hub from a reputable vendor. Some interfaces can be very picky about the ports/chipsets they work with. I know it might sound stupid, but I’ve had an old Fireface UC that only worked when connected to a TP-Link USB 3.0 powered hub. While this isn’t directly related to your Cubase issue, it’s worth a try.
If you’re open to spending a bit more, RME recommends using Sonnet USB 3.0 PCIe expansion cards with NEC/Renesas chipset. You’d need to check the forums for the exact model, but it’s one of the older Allegro Pro cards. The idea is to isolate the interface to its own chipset.
I know it might seem irrelevant since other DAWs work fine for you, but until Steinberg sorts you out, it’s worth giving it a try.
@Riggs, I just came back here with a similar idea 
. I discovered a post on the RME forum, which suggests to connect the RME interface to a dedicated USB port. The guy posting is also on a Ryzen system. So you might give Riggs advice a try. The post also links to USBView, which can be a useful tool for the endevor.
Cheers
Chriss
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An update : it’s been at least one week since I stumbled on the “no ASIO activity” issue on my end, which was occuring until recently at Cubase launch. I have started Cubase at least 10 times since, without it.
FWIW, I updated the RME driver to 1.251 (TotalMix 1.95) / Firmware 49 last 16th august and just few days after, a Windows update occured. Worth a confirmation/check, maybe, for all of you who are affected. I’ll post here if I experience again the issue .
Reminder (System/OS) : AMD Ryzen 7 3700X / Asus Prime X470-pro / 32 Gb DDR4 / 2 SSDs - Windows 10 Pro 22H2.
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Just updated everything, but the issue persists. But I’ve always had periods without any problems followed by periods where it just happens all the time and I have to reset or reconnect like 30 times in a row to make it work.
Not good… 
On my end, the issue has simply disappeared : since my last post, I probably have launched Cubase nearly twenty added times and the driver is always making the contact with it, at the start of each session. 
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I fear, it’s a timing issue during the handshake between DAW and interface. If the timing changes, the issue may disappear. I hope for the best.
@jasal82, have you tried another USB port already? This could change the timings of the connection procedure.
After switching to another USB port I had at least 15 Cubase startups without any issue. That’s going in the right direction but I’m not yet convinced that the issue is gone for good.
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From a similar thread on this forum comes a possible solution:
@jojojojojojonas , I know that you still suffer from the sound loss issue. Could you give this a try and let me know if it solves your issues as well? Thanks !
Hi @Chriss thanks for still monitoring this issue! Interesting idea, I will try resetting total mix and see if it solves my problem. I will let you know if it works 
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Hi @Chriss unfortunately the problem is still there. I dit the “total reset” in TotalMix and didn’t touch anything in TotalMix after that. Then I created an empty Nuendo session, created one audio track and inserted one of my external effects → audio engine stopped working 
Thank you for giving it a try, @jojojojojojonas . I still assume that it’s a question of timing, which lets the initial handshake between audio interface and Cubase fail. The timing can vary between USB ports. Do you have a thunderbolt port on your AMD? You could try to a USB port on an external docking station. I have also contacted RME with this issue.
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Hi @Chriss yes your explanation seems plausible based on my limited understanding, especially since the audio engine failure usually occurs with low buffer sizes and rarely with higher buffer sizes. I don’t have any thunderbolt ports but I have two 3.1 ports, I will give them a try!
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So I finally found this thread, after having searched the forum before, but with the wrong terms obviously. I have opened another thread some weeks ago because I faced the same issue with the combination of AMD Ryzen (7950X), RME-Interface (UCX) and Cubase not initializing the ASIO driver seemingly randomly (until doing a reset of the driver in Studio setup). I didn’t know that the buffer size might be involved, too, I have mine at 128 samples.
In the end, I found out that the issue was actually related to the USB port which my UCX was connected to. After doing endless tests with Cubases’ setting, recreating audio connections etc, connecting the UCX to another port seems to have solved the problem. I actually have identified two other ports which work fine (as far as I can remember after so many tests…), one which randomly, but rather reliably makes Cubase stay silent.
In my case it was a port on a “AMD USB 3.20 eXtensible-Hostcontroller”. This was a Hub that had also a mouse, camera and keyboard connected, usually I check that the audio interface is alone on a hub, but it must have slipped one time… not sure if it is relevant.
The port that worked was on a ““AMD USB 3.10 eXtensible-Hostcontroller”, no other devices connected.
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