FDA Panel Votes Against Continued Approval of Pepaxto for Myeloma Subtype

The FDA’s Oncologic Drugs Advisory Committee voted against the continued approval of Pepaxto for pretreated relapsed/refractory myeloma, based on survival data from a clinical trial.

Members of the Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee voted against the continued approval of Pepaxto (melphalan flufenamide; melflufen) for adults with pretreated relapsed/refractory multiple myeloma.

Pepaxto was granted an accelerated approval in February 2021, with continued approval being contingent upon further study findings (called post-hoc analyses), which would be discussed and voted on by the FDA’s Oncologic Drugs Advisory Committee.

The vote, which occurred last week, was 14 to 2, with the majority of experts expressing that the benefit of the drug did not outweigh potential risks.

“There’s certainly a need for better drugs … but we shouldn’t be using drugs that might actually be harming patients,” said Dr. Christopher Lieu, a medical oncologist at the University of Colorado Medicine in Aurora, during the Oncologic Drugs Advisory Committee meeting.

Of note, the Oncologic Drugs Advisory Committee is made up of more than a dozen experts across several medical fields, including oncology.

To determine if Pepaxto should continue to be approved, the Oncologic Drugs Advisory Committee members discussed results from the confirmatory phase 3 OCEAN clinical trial, which compared Pepaxto plus dexamethasone to Pomalyst (pomalidomide) and dexamethasone in pretreated relapsed/refractory myeloma.

The study missed its two main goals: the Pepaxto-containing regimen was not superior to the Pomalyst regimen when it came to progression-free survival (time from treatment until disease worsens) or overall survival (time from treatment until death of any cause).

“Accelerated approval requires that the drug provide a meaningful advantage over available therapies given,” Dr. Nicole Gormley, director of the Division of Hematologic Malignancies at the FDA, said at the Oncologic Drugs Advisory Committee meeting. “With what is currently known, we would not have granted an accelerated approval to (Pepaxto) as the concerns and issues outlined would preclude a conclusion that (Pepaxto) provides a meaningful advantage over available therapies.”

Results from OCEAN showed that the average overall survival was 19.7 months for patients given the Pepaxto-containing regimen, compared to 25 months for patients given the Pomalyst regimen.

Preliminary progression-free survival results showed that an average time to disease progression was 6.9 months and 4.9 months in the Pepaxto and Pomalyst groups, respectively. The manufacturer of the agent, Oncopeptides, also submitted further progression-free survival data that favored Pepaxto, but the committee members said that data from 29 of these patients needed to be reassessed.

However, not everyone’s experience with Pepaxto was negative. Scott Johnson, a patient with multiple myeloma who was treated with the drug for about a year at Dana-Farber Cancer Institute in Boston, spoke at the meeting, stating that Pepaxto did not cause the same fatigue and nausea that he has seen with other anti-cancer agents.

“For me, it was a positive treatment,” Johnson said. “It got me through some time and provided me with (time to live) to the next treatment.”

While the drug may benefit some patients, most voters did not feel that it should continue to be approved for the broader range of patients for which it was initially indicated.

“I do think it is possible that there is some benefit and specific subpopulations (that could benefit), but on the whole, I do not think that the benefits outweigh the risks,” said Dr. Anthony D. Sung, an associate professor of medicine at Duke Health in Durham, North Carolina.

It is important to note that the FDA does not have to follow the Oncologic Drugs Advisory Committee members’ recommendations. In fact, members of the committee voted against granting an accelerated approval to Xpovio (selinexor) in combination with dexamethasone for a certain group of patients with multiple myeloma in 2019. Months later, the FDA granted the combination the accelerated approval.

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