Place oven rack in upper third of oven and preheat to 375°F
Cook pasta for 7-8 minutes in salted boiling water then drain and set aside.
While the pasta cooks, melt the butter in a large pot over medium heat. Add flour and whisk to combine into a roux. Stir frequently until light golden brown, about 2 minutes.
Add milk and cream to the roux, and whisk until well combined and there are no lumps. Continue stirring frequently and bring to a low simmer. Cook for 3-4 minutes until the mixture is thickened, then add cheese in batches of 1-2 cups at a time, stirring until each batch is fully melted and smooth.
Season the cheese sauce with salt and pepper, then add cooked macaroni and stir gently until fully combined.
Transfer the macaroni and cheese to a 9x13 baking dish.
To make topping, melt the remaining butter in a microwave-safe dish, then pour over the panko and stir until the crumbs are well coated.
Sprinkle the topping over the macaroni and cheese, then place the baking dish in the oven. Bake uncovered for 15-20 minutes until the topping is lightly browned.