More efficacy data needed for Levo’s PWS treatment

Mari Serebov, BioWorld: November 4, 2021


Compelling testimony from parents who saw life-altering changes in their children who participated in Levo Therapeutics Inc.’s intranasal carbetocin clinical trial wasn’t enough to counter what the FDA’s Psychopharmacologic Drugs Advisory Committee saw as a lack of “substantial evidence” to support the drug’s effectiveness in treating hyperphagia associated with Prader-Willi syndrome (PWS).

Twelve committee members agreed with the FDA’s assessment Nov. 4 that the efficacy evidence doesn’t meet the regulatory bar, with only one member voting that it does. In explaining her yes vote, Alice Shapley, the committee’s patient representative, said that, encouraged by the drug’s safety profile, she took a “liberal view” of the term “substantial evidence.”

At the other end of the spectrum, James Troendle, deputy director of the Office of Biostatistics Research at the NIH’s National Heart, Lung, and Blood Institute, said the evidence Levo presented from a small phase II proof-of-concept study and a phase III study that failed to meet its primary endpoint didn’t meet even the lowest bar possible.

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Noting how regimented their children’s lives have to be and the difficulty they have coping with disruptions to routine, parents speaking at the meeting provided some insight into how challenging it is to participate in a trial. Large studies in this population are not realistic, said Susan Hedstrom, executive director of the Foundation for PWS Research. She urged the FDA to allow Levo to further study the drug while it’s being used, as it would be an undue burden to ask the community to undergo years of another clinical trial.

Diana Zuckerman, president of the National Center for Health Research, disagreed, noting that the FDA clearly told Levo what evidence would be needed, but the sponsor chose to ignore that advice. As a result, she said during her testimony, the evidence Levo presented at the adcom was among the worst she’s seen in the 100 adcoms she’s participated in. She feared it would set a bad precedence to approve the drug based on that evidence.

She encouraged Levo to spend “a few more months” to establish that carbetocin is safe and effective while maintaining patient access to the drug through the FDA’s extended access program.

“No one is asking for a perfect study,” Zuckerman said. “We’re asking for a good study” – one with an adequate number of participants studied for an appropriate length of time. It also should have more diversity. Zuckerman noted that all but one patient in the phase II trial was white.

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