A panel of outside advisors to the FDA voted 11-5 in favor of Zevra Therapeutics’ drug for a rare genetic condition called Niemann-Pick disease type C, saying that it is effective based on current data.
The drug, arimoclomol, was previously rejected by the FDA in 2021, but Zevra resubmitted an application at the end of 2023 after generating additional mouse and cell data, and reanalyzing the pivotal clinical trial results.
“Overall, the bulk of the data favored a slightly positive effect,” said advisory committee member Jonathan Mink, who voted in favor of the drug and was previously chief of child neurology at the University of Rochester. Experts who voted in favor noted that the clinical data and patient testimonies suggested the drug may help stabilize the disease, and in a few cases help improve symptoms.
Arimoclomol had succeeded in its pivotal clinical trial, but the FDA had concerns about certain measures used for the primary endpoint and asked for a new analysis when it rejected the drug. Zevra’s reanalysis included a modified primary endpoint which re-scored measures of swallowing, a skill people with Niemann-Pick type C struggle with as their diseases progress. It also removed measures of cognition, where the FDA had concerns about the reliability of the data.
Zevra also included data from an open label extension study that provided longer follow-up on patients in the original clinical trial.
The FDA convened its newly-formed Genetic Metabolic Diseases Advisory Committee on Friday to discuss whether the clinical trial data, and new mouse and cell data, showed arimoclomol was effective for treating Niemann-Pick disease type C, a progressive genetic disease that impacts a number of organs in the body. The condition is part of a group of diseases called lysosomal storage disorders, where people, often children, lack certain crucial enzymes. The FDA is not required to side with the decision of its advisory committee, but it often does.
Most advisory committee members believed the drug had an incremental treatment effect, but some also noted a challenge was teasing out arimoclomol’s effect from another drug, miglustat, which 78% of patients on the pivotal clinical trial were taking simultaneously.
Miglustat is marketed as Zavesca in the US for certain patients with Gaucher disease. The drug is approved for Niemann-Pick disease in the EU, Canada and Japan, but not in the US.
The FDA responded to advisory committee members’ concerns about approving the drug alone by noting that arimoclomol should be looked at on top of standard of care, which could include off-label use of miglustat.
“Really looking at this as added on to standard of care made a difference for me versus thinking about arimoclomol on its own,” said University of Texas Medical Branch’s Carole Tucker, who voted yes.
Sarah Chamberlain, who also voted in favor of the drug, noted that a big plus was that it appears relatively safe for patients.
“The vote no is not a vote against this continued development,” said Walter Kraft of Thomas Jefferson University, who voted no. “I do worry about approval of drugs for which there is not unequivocal evidence of efficacy. That is not without harm, also in terms of diversion of resources and activity within the space.”
A focal point of the discussion was the scales used in the primary endpoint and its reanalysis, which look at various aspects related to Niemann-Pick disease type C.
“This is rare disease and it’s messy,” said Wendy Chung, chief of the Department of Pediatrics at Boston Children’s Hospital. “These are very blunt tools that we’re seeing here, and I think that’s what’s leading to problems with the messiness.”
“What convinces me is the consistency with the data going across,” Chung said. “It does look like what I would consider clinically meaningful.”
During an open hearing, patients and family members of those with Niemann-Pick disease type C spoke out in support of approval of the drug. Those who participated in the clinical trial emphasized repeatedly the stability the drug brought to the patients’ condition, showing pictures and videos of the patients doing outdoor activities or eating.
Advisory committee members generally agreed that additional nonclinical data with mice and cells were not very convincing.
Arimoclomol was previously being developed by Orphazyme, a Danish neurodegenerative disease biotech that Zevra acquired in 2022. Orphazyme was a “meme stock” that saw very high valuations before the 2021 FDA rejection.
The FDA has until Sept. 21 to rule on arimoclomol.