Senate Health Committee Chairman Lamar Alexander Andrew (Lamar) Lamar AlexanderMcConnell locks down key GOP votes in Supreme Court fight Alexander backs vote on Trump Supreme Court nominee: What Democrats 'would do if the shoe were on the other foot' Toobin: McConnell engaging in 'greatest act of hypocrisy in American political history' with Ginsburg replacement vote MORE (R-Tenn.) faces the challenge of his career in selling a breakthrough health-care deal to skeptical Republican colleagues.

If he fails, it would be a blow not only to his reputation but perhaps also to the political prospects of the Republican Party in 2018.

The Congressional Budget Office projects health insurance premiums are projected to rise 20 to 25 percent without congressional action.

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Alexander told colleagues during an impassioned floor speech Thursday that it’s time to change course on ObamaCare and work with Democrats to reform the law instead of trying again unsuccessfully to repeal it with party-line votes.

“We’ve had about 50 votes, maybe more, and we lost them all. And we made thousands of speeches and we lost them all,” he said.

He warned that digging in the party’s heels and letting ObamaCare collapse under its own weight — a position occasionally espoused by President Trump and many conservatives — would be a mistake.

“I would ask what’s conservative about unaffordable premiums?” he said. “What’s conservative about creating chaos so millions can’t buy health insurance?”

It was a wake-up call from a lawmaker who has primary jurisdiction over health-care policy and is widely respected for his expertise and even-keel demeanor.

Alexander’s deal with Sen. Patty Murray Patricia (Patty) Lynn MurrayTrump health officials grilled over reports of politics in COVID-19 response CDC director pushes back on Caputo claim of 'resistance unit' at agency The Hill's Morning Report - Sponsored by The Air Line Pilots Association - Pence lauds Harris as 'experienced debater'; Trump, Biden diverge over debate prep MORE (Wash.), the senior Democrat on the Health Committee, would extend ObamaCare’s insurance stabilization payments in exchange for giving states more flexibility to waive federal regulations.

Colleagues said Alexander is providing leadership at a time when Trump is sending mixed signals on heath care and GOP leaders in Congress are eager to escape from the issue and move on to tax reform.

“He’s leading,” said Sen. Lisa Murkowski Lisa Ann MurkowskiMcConnell locks down key GOP votes in Supreme Court fight Most Americans think winner of election should pick next Supreme Court justice: poll Murkowski: Supreme Court nominee should not be taken up before election MORE (R-Alaska), who is backing the agreement with Murray.

“He has an ability to distill complex issues into a few key points and keep us focused on that,” she said of Alexander. “He’s demonstrated real strength of leadership in an area where we were kind of navigating blindly.”

“Lamar is highly regarded by every senator, both Republicans and Democrats, and he is capable of bringing people to his side because of his knowledge and the respect people have for him,” said Sen. Jerry Moran Gerald (Jerry) MoranLobbying world This World Suicide Prevention Day, let's recommit to protecting the lives of our veterans Hillicon Valley: Zuckerberg acknowledges failure to take down Kenosha military group despite warnings | Election officials push back against concerns over mail-in voting, drop boxes MORE (R-Kan.).

But Alexander appeared to be out of sync with his party earlier in the week after Trump and Speaker Paul Ryan Paul Davis RyanKenosha will be a good bellwether in 2020 At indoor rally, Pence says election runs through Wisconsin Juan Williams: Breaking down the debates MORE (R-Wis.) indicated they would not support his deal with Murray.

Rep. Mark Walker (R-N.C.), the chairman of the Republican Study Committee, a group of more than 150 House Republicans, panned it as a bailout for insurance companies.

“The GOP should focus on repealing and replacing ObamaCare, not on trying to save it,” he wrote on Twitter.

Senate Majority Leader Mitch McConnell Addison (Mitch) Mitchell McConnellOcasio-Cortez to voters: Tell McConnell 'he is playing with fire' with Ginsburg's seat McConnell locks down key GOP votes in Supreme Court fight Video shows NYC subway station renamed after Ruth Bader Ginsburg MORE (R-Ky.), one of Alexander’s closest friends in the Senate, kept his distance.

The leader has yet to announce his position and didn’t even mention it to reporters Tuesday after Alexander unveiled it in a private lunch with GOP colleagues.

The lack of initial buy-in from Trump and House Republicans has puzzled and dismayed some of Alexander’s Senate colleagues.

“What I would have expected, that doesn’t appear to be the case, is that before we went down another health-care path, we’d have a better sense of that conclusion being acceptable to the House and the White House,” said Moran.

Trump’s tweet seemed to catch Alexander off guard, especially since the president called him directly last week to encourage him to work on a bipartisan proposal to shield people from projected premium increases.

Colleagues say Trump’s zigging and zagging on the issue must be frustrating for Alexander.

“It’s got to be frustrating for him to know that he was moving to a place that the administration supported until maybe even one person expressed concern and the president changed his mind,” said Sen. Bob Corker Robert (Bob) Phillips CorkerHas Congress captured Russia policy? Tennessee primary battle turns nasty for Republicans Cheney clashes with Trump MORE (R-Tenn.), Alexander’s home-state colleague and a close friend.

Other Republicans say Alexander doesn’t appear to have a grasp on the politics of the House, where anything seen as shoring up ObamaCare is likely to draw fire from conservatives.

Asked if Alexander was out of step with House Republicans, Sen. Ron Johnson Ronald (Ron) Harold JohnsonGOP set to release controversial Biden report Democrats fear Russia interference could spoil bid to retake Senate The Hill's Morning Report - Sponsored by The Air Line Pilots Association - White House moves closer to Pelosi on virus relief bill MORE (R-Wis.) said, “Just based on the communication coming out of the House since yesterday, I would say that’s an accurate assessment.”

But he emphasized, “I’m supportive of what Lamar and Patty are trying to do.”

Johnson said, “It’s unfortunate what’s happened over the last day in terms of the rhetoric,” noting that conservatives are already framing it as “bailing out insurance companies.”

Former Sen. Judd Gregg (R-N.H.), who has remained close friends with Alexander since retiring from Congress, says Republicans should be cheering his work instead of slamming it as propping up ObamaCare.

“There’s such a myopic view of things in Washington where people get onto their high horse and proclaim purity is the only way forward,” Gregg said.

“This is a significant step forward in turning things back to the states. Lamar is giving the Republicans an escape hatch from disaster that was their performance on health care so far,” he added.

The outlook for Alexander brightened on Thursday when he announced on the floor that 11 Republican colleagues had decided to back the legislation, including Murkowski, Sen. John McCain John Sidney McCainMomentum growing among Republicans for Supreme Court vote before Election Day McConnell urges GOP senators to 'keep your powder dry' on Supreme Court vacancy McSally says current Senate should vote on Trump nominee MORE (Ariz.) and Sen. Susan Collins Susan Margaret CollinsMcConnell locks down key GOP votes in Supreme Court fight Most Americans think winner of election should pick next Supreme Court justice: poll Murkowski: Supreme Court nominee should not be taken up before election MORE (Maine) — the lawmakers who sunk the GOP health-care bill in July.

Then Trump changed his mind, telling reporters, “If they can do something, I’m open to it.”

Trump praised the emerging deal as something that would protect people from premium increases over the next two years and give Congress time to pass legislation converting ObamaCare into block grants for states.

If the president gets solidly behind Alexander’s proposal, there’s a better chance that he’ll be able to sell it to Ryan and House Republicans.

Murkowski, who has clashed with Trump on health care, said Alexander is putting together a plan to avoid turbulence in the health-care market.

She thinks many GOP colleagues are likely breathing a sigh of relief at the sight of a rescue plan, even if they haven’t yet come out in support of it publicly.

“There’s nothing good that comes with causing turmoil. We’ve got an obligation to keep the turmoil from happening or getting worse,” she said. “Standing by and doing nothing makes the situation worse for families that are really vulnerable."

Murkowski said McConnell showed a lot of confidence in Alexander by giving him room to work out a deal with Murray and expects he and other Senate GOP leaders will back it eventually.

“Leader McConnell is in the same place that I am in having a desire to make a positive difference for people when it comes to the current health-care situation,” she said. “Alexander asked for the space from the leadership to see if he could knit something together. Our leader gave him that."

“Sometimes he gives others the space to find the solution and advance the solution, and that’s what Leader McConnell has done,” she added. “My hope is that not only Leader McConnell but the entire leadership team will be on board.”

Still, Alexander has his work cut out for him.

It’s telling that none of the bill’s co-sponsors are running for reelection next year. Conservative primary challengers are likely to criticize a vote in favor of it as a vote to fix ObamaCare.