CLEVELAND—A $260 million late-night settlement between four drug companies and two Ohio counties averted a trial here over who is to blame for the opioid crisis, clearing the way for broader talks aimed at resolving thousands of opioid-addiction cases nationwide.

Lawyers for the plaintiffs and companies said the settlement could be an important step toward a multibillion-dollar deal that brings closure to 2,500 lawsuits and sends needed money to communities hard-hit by opioid addiction.

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