Oncologists vs. the FDA and RFK Jr.

Robert F. Kennedy Jr. doesn’t like our criticism of the Food and Drug Administration’s rejection of Replimune’s life-saving drug for metastatic melanoma. But the Health and Human Services Secretary’s statements at a House hearing last Thursday were as bewildering as the FDA rejection.

“Every panel within FDA, all the career panels, the career scientists who looked at that drug said it was not effective,” he said. That isn’t true. The initial panel that reviewed Replimune’s RP1 recommended approval. It was overruled by FDA biologics chief Vinay Prasad.

After an uproar among oncologists, the FDA last fall agreed to reconsider RP1 and selected a second panel to eliminate what it called “bias.” Dr. Prasad believed the first panel was biased because it recommended the drug. So he tapped new reviewers who shared his bias against the drug. But even these reviewers didn’t say the drug wasn’t effective.

The FDA rejection letter instead said it is unclear whether the drug was effective based on contrived reasoning that Mr. Kennedy parroted: Replimune only did a “one arm trial, and all the people who were tested also received a chemotherapy drug, so we don’t know what the effect was,” Mr. Kennedy said. Fact-check: No patients in the trial received chemotherapy.

They were given the RP1 oncolytic virus therapy, in addition to an anti-PD-1 immunotherapy that is a first-line melanoma treatment. However, the cancer had worsened for all patients in the trial on an anti-PD-1 immunotherapy. It would have thus been unethical to give some patients an anti-PD-1 drug alone merely to serve as a control group.

RP1 was given in combination with an anti-PD-1 drug because its aim is to activate the immune response, and in doing so overcome resistance to other immunotherapies. FDA reviewers would have understood all this had they consulted melanoma doctors who tell us the RP1 rejection makes no sense and will cost thousands of lives.

Anna Pavlick, a doctor at New York’s Weill Cornell Medicine who has researched melanoma for 25 years, treated patients in the trial. “Honestly, there was no doubt in our minds whatsoever when we completed this study and we saw the results, that this was going to be approved as a wonderful alternative for our patients because they have no options,” she tells us.

She says cancer will eventually advance in about 60% of metastatic patients who are on a first-line anti-PD-1 drug. Doctors typically then give a checkpoint inhibitor or targeted drug if patients have a particular mutation, but many still continue to show cancer progression. At that point, their options are chemotherapy, which is rarely effective, or to enroll in a trial for an experimental treatment.

“Lord knows I’ve given enough chemotherapy in my lifetime to melanoma patients to know how dismal that outcome is,” Dr. Pavlick says. Remarkably, a third of patients who failed to respond to a standard anti-PD-1 regimen went into remission with RP1. “I have patients who have been treated with this drug that are still alive today who would otherwise be dead,” she says. The FDA claimed the anti PD-1 drug, not RP1, might have been the reason patients went into remission. That’s “ ludicrous,” Dr. Pavlick says. “These are patients that hands down progressed on anti-PD-1.” She calls FDA’s demand for a control group “completely unethical” since “they’re progressing on that treatment”—that is, their cancer is getting worse.

Melanoma doctors were “all pretty horrified with the rejection the first time around,” she adds. But they figured that “with further analysis and answering the FDA’s questions, it would surely be approved.” Melanoma doctors organized and sent a letter to the FDA imploring it to approve RP1.

“Pharma didn’t ask us to do that,” she says. “We were all floored that it did not get approved the first time, that we felt we needed to do everything humanly possible to try to get this approved for our patients.” By banding together, she says, they hoped their voices “would be heard at the FDA, which in fact, obviously they were not.”

Eric Whitman, a melanoma doctor at the Atlantic Health System Cancer Care, echoed her view on RP1’s rejection. He has treated several patients with RP1 under the FDA’s expanded access program. The program lets doctors petition the FDA and a drug maker to prescribe an experimental medicine outside of a clinical trial. Dr. Whitman says cancer had worsened on every available treatment one of his patients had tried, including other experimental ones in clinical trials, but went into remission with RP1.

“When you talk to the melanoma experts, people who treat lots and lots of melanoma patients like myself, it’s obvious that this is beneficial to patients and it’s saving lives or it has potential to save lives,” he says. “The community of patients and doctors don’t understand the reasoning.”

Erin Pazour of Cedar Rapids, Iowa, received RP1 in the trial after her cancer worsened on an anti-PD-1 drug. After eight rounds of treatment with RP1, she has been cancer free since February 2023. She was able to work full-time as a physical therapist during her treatment because side effects were minimal. “It’s unfortunate that others won’t have access to such a life-changing medication,” she says.

Mr. Kennedy said at the hearing that FDA Commissioner Marty Makary “made the correct decision to not approve that drug” and was getting flak because “he’s trying to do change.” Denying patients a life-saving medicine for inexplicable reasons is the wrong kind of change. If Dr. Makary doesn’t understand that, the FDA needs a change in leadership.