Istio Ingress Gateway RDS sync state STALE (Never acknowledged)

With istio 1.5 upgrade, when spin up new cluster, everything works fine, but after deploying more applications, we are seeing ingress gateway RDS sync showing STALE (Never acknowledge), with 404 error and response flag as NR when accessing services.

Tried increasing cpu requests for both pilot and envoy, but still no luck.

Any pointers on how to troubleshoot this or suggestions?

stale means that Istiod has sent an update to Envoy but has not received an acknowledgement. This usually indicates a networking issue between Envoy and Istiod or a bug with Istio itself.
See this

May this will helps you.

Appears to be a bug, when any virtual service has regex with negative pattern matching (?!). Created a bug here