LAHAINA, Hawaii — Trade negotiators from the United States and 11 other Pacific nations failed to reach final agreement on Friday, with difficult talks on the largest regional trade agreement ever deadlocking over protections for drug companies and access to agriculture markets on both sides of the Pacific.

Trade ministers, in a joint statement, said late Friday they had made “significant progress” and will return to their home countries to obtain high-level signoffs for a small number of final sticking points on the agreement, the Trans-Pacific Partnership, with bilateral talks reconvening soon.

“There are an enormous number of issues that one works through at these talks, narrowing differences, finding landing zones,” said Michael B. Froman, the United States trade representative. “I am very impressed with the work that has been done. I am gratified by the progress that has been made.”

Still, the breakdown is a setback for the Obama administration, which had promoted the talks here as the final round ahead of an accord that would bind 40 percent of the world’s economy under a new set of rules for commerce.