The Senate rejected a scaled-back ObamaCare repeal bill in the early hours of Friday in a shocking vote that marks a major defeat for GOP leaders and the seven-year effort to repeal the healthcare law.

The Senate voted 49-51 against the "skinny" bill, which would have repealed ObamaCare's individual and employer mandates and defunded Planned Parenthood.

Sen. John McCain (R-Ariz.) provided the crucial vote against the bill, alongside GOP Sens. Susan Collins (Maine) and Lisa Murkowski (Alaska).

A succession of Republicans attempted to appeal to McCain, as well as Murkowski, on the Senate floor while the preceding vote was held open long after it usually would have closed.

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Vice President Pence and Sen. Jeff Flake, also of Arizona, were among those who went to talk to McCain.

"We all wanted to try to get to a positive outcome," Murkowski said after the vote. "It's very disappointing that we weren't able to."

McCain, who returned to the Senate this week after learning he had brain cancer last week, said in a statement after the vote that he wanted to go back and use the committee process, while working with Democrats on healthcare.

“We must now return to the correct way of legislating and send the bill back to committee, hold hearings, receive input from both sides of the aisle, heed the recommendations of nation’s governors, and produce a bill that finally delivers affordable health care for the American people,” McCain said in the statement.

Republicans cast the so-called skinny bill as a way to keep their repeal hopes alive and get to negotiations with the House.

Now, it appears that Republican hopes of repealing ObamaCare have been quashed.

In a speech from the Senate floor early Friday morning after the surprise failed vote, Majority Leader Mitch McConnell (R-Ky.) said "it is time to move on."

"What we tried to accomplish for the American people was the right thing for the country," McConnell said. "I think the American people are going to regret that we couldn't find another way forward."

Moving forward, McConnell invited Democrats to offer their ideas, but he seemed skeptical, saying that “bailing out insurance companies” would not be acceptable.

“Now I think it’s appropriate to ask, what are their ideas?” McConnell said. “It’ll be interesting to see what they suggest as the way forward.”

Democratic requests include providing funding to lower premiums for high-cost enrollees, known as reinsurance, and guaranteeing key ObamaCare payments known as cost-sharing reductions.

President Trump reacted on Twitter, saying the three Republicans and Democrats who all voted against the bill had let the country down.

3 Republicans and 48 Democrats let the American people down. As I said from the beginning, let ObamaCare implode, then deal. Watch! — Donald J. Trump (@realDonaldTrump) July 28, 2017

The president has threatened to cancel the cost-sharing reduction payments and appeared to do so again. “As I said from the beginning, let ObamaCare implode, then deal. Watch!” Trump tweeted.

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"We're not adverse to that, I just don't have high hopes that we're really going to get anything that solves the problem that we think exist with ObamaCare,” Thune said.

Ahead of the vote, many GOP senators admitted that the measure was not good policy but, in a highly unusual situation, said they were voting for it simply to advance the process and set up a conference committee with the House to negotiate a new bill.

But some Republicans harbored fear that a conference committee could fail and that the House could eventually just take up the scaled-down bill and send it to the president.

Insurers and many healthcare experts warned that by repealing the mandate to have insurance without a replacement, the bill would significantly destabilize health insurance markets and spike premiums.

The Blue Cross Blue Shield Association warned of “steep premium increases and diminished choices that would make coverage unaffordable and inaccessible.”

The Congressional Budget Office found that the bill would result in 16 million more uninsured people and roughly 20 percent higher premiums, largely from repealing the mandate to have insurance.

Republicans pointed out that without the mandate many of those people would choose not to buy insurance.

Sen. Lindsey Graham (R-S.C.) warned that if the bill became law it would “collapse the individual market.” But he said he received assurances from Speaker Paul Ryan (R-Wis.) that the House would not just pass the bill and there would be a conference committee.

The process for sending the bill to the floor was highly unusual. GOP leaders released the text of the bill just hours before the final vote, a decision widely denounced by Democrats.

With the bill’s failure, some expressed hope about bipartisanship.

"I hope so,” said Sen. Bill Cassidy (R-La.). “I have tried in the past, as has [Collins], to have a dialogue. It hasn't worked. Maybe this had to happen to begin to have a conversation.”

Updated at 6:56 a.m. Rachel Roubein and Jordain Carney contributed to this report