A trio of key Democrats announced Tuesday they will oppose the party’s plan to lower drug prices, creating a significant roadblock for Democrats’ desired $3.5 trillion tax and spending package.

Reps. Scott Peters (D-Calif.), Kathleen Rice (D-N.Y.) and Kurt Schrader (D-Ore.) said they will oppose drug-pricing changes that would allow Medicare to negotiate lower prices and that have become the framework to pay for many of Democrats’ sought-after measures this year. The three lawmakers are members of the House Energy and Commerce Committee, one of several panels debating the budget reconciliation package, and say they have concerns about a plan to empower Medicare to negotiate directly with drug companies.

The drug-pricing changes are widely regarded as a linchpin to a broader set of health-care changes that Democrats hope to enact, with the savings on federal pharmaceutical spending helping to pay for the rest. The pharmaceutical industry and Republicans have staunchly opposed the drug-price plan, arguing it will hurt the industry’s ability to develop drugs — an argument echoed Tuesday by the Democratic holdouts.

“I support many of the proposals being considered this week, but I do not support advancing policies that are not fiscally responsible and jeopardize the bill’s final passage,” Rice said in a statement.

“I want to be clear — I support Medicare drug price negotiations,” Schrader said in a statement Tuesday, but he introduced a rival proposal that would limit Medicare’s power to negotiate to “the most expensive subset of drugs on the market.”

Patient advocates and most congressional Democrats have argued that allowing Medicare — the national health insurance program for older Americans — to use its bargaining power would drive down U.S. drug prices.

While Democrats’ drug-pricing plan can still advance to a floor vote in the House, the three members’ opposition puts the broader reconciliation package at risk and may force leaders to compromise on its provisions. Democrats cannot lose another vote for the drug-price plan if it is to be included in their massive social spending package, known as the Build Back Better Act, and other centrist members of the party have signaled they have their own sets of concerns.

House Democrats have pinned their reconciliation strategy on enacting measures contained in legislation passed by the House in 2019 called H.R. 3; that legislation died in the Senate. The Democrats cite Congressional Budget Office projections that the bill’s drug-negotiation provisions would lower drug prices and cut federal spending by $456 billion over a decade. Those savings could then be used to broaden the social safety net, such as by offering additional Medicare benefits and allowing more people to enroll in Medicaid, the government’s health insurance program for low-income Americans, party leaders argue.

H.R. 3 “called for using savings from the negotiation for prescription drug prices — the savings from that to be used for expanding dental, visual and hearing benefits for seniors,” House Speaker Nancy Pelosi (D-Calif.) said last week. “We’re all for that.”

On the other side of the Capitol, Senate Finance Committee Chairman Ron Wyden (D-Ore.) is hashing out a drug-price negotiation plan of his own — and also must try to thread a needle between the moderate and liberal wings of his caucus.

While H.R. 3 passed the House in a 230 to 192 vote in December 2019, Democrats have since lost seats in the chamber. They can afford only three defections in the House and none in the Senate if they are to pass the Build Back Better Act.

Republicans have been unified in their opposition to the reconciliation plan, which can pass with a simple majority in both chambers.

Democrats have sought to tamp down perceptions of infighting as their reconciliation package proceeds.

“Democrats are committed to leveling the playing field and reining in the soaring cost of prescription drug prices for the American people,” said C.J. Young, a spokesman for Democrats on the House Energy and Commerce Committee.

Congressional aides noted that the House Ways and Means Committee can still advance the drug-price plan for a floor vote, even if the measure stalls in the Energy Committee.

Advocacy groups have pressed Democrats to remain in lockstep on the drug-pricing provisions. The group Patients for Affordable Drugs Now targeted Peters and Schrader in ads this summer, exhorting them to support H.R. 3 after they raised concerns about the legislation, and on Tuesday the group released new polling data commissioned by the organization that showed strong support for drug-price negotiations in the three holdout lawmakers’ districts.

Some groups also castigated the pharmaceutical industry Tuesday, suggesting the deep-pocketed sector had helped fuel some Democrats’ resistance to drug-pricing measures.

“This is David and Goliath,” said Frederick Isasi, executive director of Families USA, a liberal consumer health lobby. “The drug companies are one of the wealthiest industries in the world. They spend more lobbying than any other industry.”

Pharmaceutical industry officials argued that lawmakers such as Peters, who voted for H.R. 3 in 2019, have independently reconsidered the plan after Democrats secured unified control of Congress and the White House and Washington’s political realities shifted.