Will Major New FDA Law Include Accelerated Approvals Process?

US lawmakers are under pressure this month to decide whether to proceed with reforms to the accelerated approval pathway for medicines, with advocates arguing for a need for speedier confirmatory trials.

At issue are attempts to give the US Food and Drug Administration (FDA) more leverage to ensure that medicines that receive rapid clearance actually do provide the expected benefit for patients.

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

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

However, Sen. Richard Burr (R-NC) has proposed leaving this provision out of the bill, raising concerns among some advocates that the changes to the accelerated approvals pathway may be abandoned this year.

The nonprofit group Doctors for America is asking its members to ask their lawmakers to support the accelerated approvals changes proposed for PDUFA.

“We went from a bipartisan package with support for these reforms to now a conversation about stripping all that from the user fee legislation,” Reshma Ramachandran, MD, MPP, MHS, who serves as the chair of the group’s FDA Task Force, told Medscape Medical News.

Strenghthening the FDA’s Stance

The House in June passed a reauthorization of PDUFA that includes provisions meant to beef up the FDA’s management of accelerated approvals. The bill would allow the FDA to require that companies begin post-approval studies before a drug that has been cleared by accelerated approval goes on the market. It also calls for greater transparency in drug labeling and a streamlining of the process by which the FDA removes products from the market when companies have failed to act with due diligence to conduct studies or where studies have failed to show a benefit to patients, according to House Energy and Commerce Chairman Frank Pallone, Jr. (D-NJ).

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 draft PDUFA bill in a 13 to 9 vote. This package contained provisions meant to speed studies needed to confirm whether medicines cleared by accelerated approvals work as expected.

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

PDUFA is popular with members of both parties and is considered a must-pass measure, inasmuch as the user fees that drugmakers pay for applications for their products fund the review operations and shorten the timeline for clearances.

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

Politico quoted an unidentified congressional aide as saying: “The ‘Burrs’ have all this leverage right now with the power of just saying ‘no,’ they’ve anchored a position with the clean user fee package…. They get to enjoy slowly adding things on by way of negotiation with the ‘Murrays.’ “

The current PDUFA law expires September 30. Congressional leaders might opt to extend the current law by adding a stopgap extension to the budget measure this month, several news outlets, including Politico, STAT, and Endpoints News, have reported.

Clinicians who support the accelerated approval reforms should act quickly to let legislators know why they matter, said Michael A. Carome, MD, director of the Health Research Group for the nonprofit organization, Public Citizen.

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

Lingering Doubt

Ramachandran was among the experts who appeared at a March congressional hearing concerning the accelerated approval pathway.

Physicians are counting on the FDA to limit as much as possible the period of uncertainty for drugs cleared by accelerated approvals, Ramachandran said.

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

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

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

Sometimes, though, accelerated approvals prove to have been the wrong call.

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

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

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

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

This rising tally reflects in part the rapid advance in knowledge about targeting cancer and a recent step-up in the cancer division’s policing of approvals, said Mikkael Sekeres, MD. He is the author of the forthcoming book, Drugs and the FDA: Safety, Efficacy, and the Public’s Trust (MIT Press). Sekeres served on the Oncologic Drugs Advisory Committee that in 2011 voted against bevacizumab for breast cancer.

“In some cases, accelerated approval is a magnificent mechanism to get highly active drugs to desperate patient populations who have no other options,” Sekeres told Medscape Medical News. But it has “been used more and more for pharmaceutical companies trying to game the system and get drugs approved quicker.”

For oncologists such as Sekeres, these accelerated approvals create challenges in managing patients while they wait to learn whether these cancer medicines work as hoped.

“At the end of the day, we don’t know that we’ve actually made people live longer or live better” with drugs for which confirmatory evidence is not yet available, Sekeres said.

“And it’s very hard to explain that to a patient who may have gone onto patient advocacy websites” and read enthusiastic accounts of new science employed in developing the as-yet unproven drug, he said.

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

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