Will major new FDA legislation include an expedited approval process?

US lawmakers are under pressure this month to decide whether to make reforms to the fast-track drug approval pathway, with advocates arguing the need for faster confirmatory trials.

The problem lies in attempts to give the US Food and Drug Administration (FDA) more leverage to ensure that drugs that receive rapid approval actually deliver the expected benefits for patients.

Steps have been taken to incorporate this into the Prescription Drug User Fee Act (PDUFA), which is being reauthorized. The current law expires on September 30. It is considered a must-have bill because the PDUFA has resulted in a steady stream of funding from the pharmaceutical industry for the FDA’s review division.

There is strong bipartisan support in the House to address the expedited approval process in the new version of the PDUFA.

However, Sen. Richard Burr (R-NC) has moved to omit the provision from the bill, raising concerns among some advocates that changes to the fast-track approval pathway could be scrapped this year.

The nonprofit group Doctors for America is asking its members to ask their legislators to support the proposed expedited approval changes for PDUFA.

“We have gone from a bipartisan package with support for these reforms to now a conversation about removing all of this from user fee legislation,” said Reshma Ramachandran, MD, MPP, MHS, who chairs the group’s FDA working group. Medscape Medical News.

Strengthen the position of the FDA

The House in June passed a new PDUFA authorization that includes provisions intended to strengthen the FDA’s handling of expedited approvals. The bill would allow the FDA to require companies to begin post-approval studies before a drug that has been cleared by expedited approval is released to market. It also calls for greater transparency in drug labeling and streamlining the process by which the FDA removes products from the market when companies have not acted with due diligence to conduct studies or when studies do not haven’t shown benefit to patients, according to Frank Pallone, Jr. (D-NJ), president of House Energy and Commerce.

The House PDUFA bill passed 392 to 28, with 176 Republicans supporting it.

But the Senate has yet to pass its version of a PDUFA reauthorization.

The Senate Health, Education, Pensions, and Labor (HELP) Committee in June approved a PDUFA bill by a vote of 13 to 9. The package contained provisions intended to expedite the studies needed to confirm whether the drugs authorized by expedited approvals work as intended.

However, in July, Burr introduced a competing PDUFA reauthorization bill that did not contain these provisions. He said his bill “represents the clearest path” to finalizing the PDUFA update.

The PDUFA is popular with members on both sides and is seen as a must-have measure, as the user fees drugmakers pay for their product applications fund review operations and shorten the timeline for ‘permission.

The threat of a hiatus in PDUFA funds raises the threat of layoffs for FDA review staff. Politico reported that Burr staffers have been in talks in recent weeks with those who work for Senate Health, Education, Labor and Pensions Chair Patty Murray (D-WA).

Politico quoted an unidentified congressional aide as saying, “The ‘Burrs’ have all this leverage right now with the power to just say ‘no,’ they’ve entrenched a position with the clean-use fee package… They are enjoying slowly adding things by way of negotiation with the “Murrays.”

The current PDUFA law expires on September 30. Congressional leaders could choose to extend the current law by adding an interim extension to the budget measure this month, multiple news outlets, including Politico, STAT and Endpoints News, reported.

Clinicians who support fast-track approval reforms should act quickly to let lawmakers know why they matter, said Michael A. Carome, MD, health research group director for the nonprofit organization Public Citizen.

“Now is the time to push their senators or members of the House to move forward with these provisions,” he said. Medscape Medical News.

Persistent doubt

Ramachandran was among the experts who appeared at a March congressional hearing regarding the fast-track approval pathway.

Doctors rely on the FDA to limit the period of uncertainty as much as possible for drugs cleared through expedited approvals, Ramachandran said.

In the period between the expedited approval granted and the results of known confirmatory trials, patients are taking drugs that may have ultimately put them at physical and financial risk without benefiting them, she said.

“As a clinician, I just want to be sure the drug actually works,” Ramachandran told the House Energy and Commerce Committee health panel.

Sometimes these fast clearances work well, as in the case of capmatinib (Tabrecta), used to treat a type of lung cancer. It took a little over 2 years for the FDA to convert the accelerated approval of this drug to regular approval.

Sometimes, however, fast-track approvals turn out to have been the wrong decision.

Eli Lilly announced in 2019 the withdrawal of olaratumab (Lartruvo) for certain sarcomas following the failure of a confirmatory study. At that time, the drug, which received accelerated approval from the FDA in 2016, had been on the market for about 3 years. In this case, the company forfeited steps it could have used to try to keep the drug on the market.

Lartruvo’s approval was officially withdrawn in 2020, a year that marks something of a turning point for the FDA’s cancer division.

From 2011 to 2013, six accelerated cancer drug approvals were withdrawn. The first such case was the highly controversial withdrawal of an indication for bevacizumab (Avastin) in breast cancer in 2011.

Since 2020, 15 accelerated cancer drug approvals have been withdrawn, including six this year alone.

This growing tally partly reflects the rapid advance of knowledge about cancer targeting and a recent intensification of approval scrutiny by the Cancer Division, said Mikkael Sekeres, MD. He is the author of the forthcoming book, Drugs and the FDA: Safety, Effectiveness and Public Trust (MIT Press). Sekeres served on the oncology drug advisory committee that in 2011 voted against bevacizumab for breast cancer.

“In some cases, accelerated approval is a magnificent mechanism for delivering highly potent drugs to desperate patient populations who have no other options,” Sekeres said. Medscape Medical News. But it was “increasingly used by pharmaceutical companies trying to game the system and get drugs approved faster.”

For oncologists like Sekeres, these accelerated approvals create challenges in managing patients while they wait to find out if these cancer drugs are working as expected.

“At the end of the day, we don’t know if we actually made people live longer or better” with drugs for which no confirmatory evidence is yet available, Sekeres said.

“And it’s very difficult to explain that to a patient who may have gone to patient advocacy websites” and read glowing accounts of the new science used to develop the as yet unproven drug, a- he declared.

Kerry Dooley Young is a freelance journalist based in Washington, DC. She is also responsible for the central theme of patient safety for the Association of Health Care Journalists (AHCJ). Follow her on Twitter at @kdooleyyoung.

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