The main challenge a direct sequel faces is that the very selling point of the movie is undone at the end, with Pikachu and Reynolds separating. The film absolutely hinges on the talking Pikachu. Not just because Ryan Reynolds did a fantastic job with the comedy, but also because it allows a Pokémon to be a main character/dialogue partner, and it allows communication with otherwise unintelligible Pokémon via translation. And having all Pokémon talk would be wrong too, even if only the main character could understand them. Putting Reynolds back in the same Pikachu would also be a bit of a jerky move, as the end of the movie implied that the Pikachu in question only "borrowed" Reynolds its body, and that it really is a whole separate sentient being who'd rather be in control of its own body unless it's an absolute emergency. So the problem with making a sequel to the talking Pikachu movie is that by the end, the Pikachu isn't talking anymore. And unless they feature Reynolds's character (which, admittedly, wouldn't be a bad choice considering his character's profession as a detective - you could easily have another Pokémon mystery be the core of the plot), Reynolds is out too, and he was a big selling point. There's also the question of whether "human Reynolds interacting with Pokémon" would be as interesting/marketable as "Reynolds as a Pokémon". So, bit of a tricky spot there.
The other option is to change the concept of the movie entirely for the sequel, telling an entirely different story with different characters, and only keeping the Pokémon setting. In other words, not doing a sequel at all, merely another live action Pokémon movie. At a glance, it is tempting to do what the Anime does and adapt the story of the games, which I would advise strongly against. The games are set up so that a (very long) string of battles and some simple navigation leads you to the end, which would be really repetitive to show on film. Not to mention that you'd necessarily have to cut out a lot, because there's no way one can start with a trainer with a lone starter Pokémon and show the entire journey until they beat the Champion with a six-Pokémon team within the runtime of a movie without skipping over huge chunks of what happened in between. Pokémon Origins tried that, and it had very little character development and showed very little battling. It turns out that what happens along the way is more important than a snapshot of the beginning and the end of the journey, and there's no way it can all be shown in a movie. In a TV series, maybe, but the Anime is already doing that (and what a "fine" job it does with it at that...).
So yeah, a sequel movie would have to accept a radically different premise no matter what happens. Either, they'll have to drop Reynolds or find something else for him to do, and neither of the options seem to have as much promise as the original has. Doing a sort of reboot with Reynolds as a totally different talking Pikachu might be an option too, but a little confusing. It will be interesting to see where they go, though.
The other option is to change the concept of the movie entirely for the sequel, telling an entirely different story with different characters, and only keeping the Pokémon setting. In other words, not doing a sequel at all, merely another live action Pokémon movie. At a glance, it is tempting to do what the Anime does and adapt the story of the games, which I would advise strongly against. The games are set up so that a (very long) string of battles and some simple navigation leads you to the end, which would be really repetitive to show on film. Not to mention that you'd necessarily have to cut out a lot, because there's no way one can start with a trainer with a lone starter Pokémon and show the entire journey until they beat the Champion with a six-Pokémon team within the runtime of a movie without skipping over huge chunks of what happened in between. Pokémon Origins tried that, and it had very little character development and showed very little battling. It turns out that what happens along the way is more important than a snapshot of the beginning and the end of the journey, and there's no way it can all be shown in a movie. In a TV series, maybe, but the Anime is already doing that (and what a "fine" job it does with it at that...).
So yeah, a sequel movie would have to accept a radically different premise no matter what happens. Either, they'll have to drop Reynolds or find something else for him to do, and neither of the options seem to have as much promise as the original has. Doing a sort of reboot with Reynolds as a totally different talking Pikachu might be an option too, but a little confusing. It will be interesting to see where they go, though.