US Senator John McCain announced his opposition to the latest Republican attempt to replace Barack Obama's signature health care law, likely dooming the repeal effort.

It is the second time in two months that he has defied his party and President Donald Trump over efforts to replace the Affordable Care Act, often referred to as "Obamacare," which has long been in Republicans' sights.

"I cannot in good conscience vote for the Graham-Cassidy proposal," McCain said of the bill proposed by fellow Republican senators Lindsey Graham and Bill Cassidy, adding he believed health reform legislation needed to be a bipartisan effort.

President Trump, speaking in Alabama late Friday, acknowledged the setback but vowed to fight on.

"I have to tell you, maybe - it's a little tougher without McCain's vote," he said at a rally in Huntsville.

"You get knocked down and then the bad ones stay on the stool and they say 'We quit, we quit.' The great ones get up and they end up winning. That's what we are going to do."

In July, McCain made a dramatic return to Washington from Arizona after a brain cancer diagnosis to become one of three Republican senators who helped sink their party's earlier bid to replace Obamacare.

Now, rebels within the party ranks appear set to torpedo what may be the party's last chance to make good on a longstanding Republican goal, and a signature pledge of the president.

With both McCain and the conservative Rand Paul opposed, it would take just one more Republican defector to prevent the bill's passage before a deadline of September 30, the end of the fiscal year. At least two party moderates - Susan Collins and Lisa Murkowski - are known to have serious reservations.

The bill's collapse would be yet another blow to the president and the Republican leadership, who have been unable to move forward on repealing Obamacare despite controlling Congress and the White House.

Source: Khaleej Times