Ahead of an advisory meeting Friday, the FDA raised questions about the strength of human, mouse and cell data Zevra Therapeutics generated for its treatment for Niemann-Pick disease type C — a rare, progressive genetic disease where fatty molecule buildup damages various parts of the body.
Zevra resubmitted an application for the drug, arimoclomol, after the FDA rejected it in 2021. The drug is based on a synthetic chemical derivative and is administered to patients three times a day.
The agency said that Zevra’s new clinical trial analysis using a revised scale “appear[s] to show a trend toward slower progression” in patients who received arimoclomol compared to placebo at one year — a positive signal for the company. According to the agency’s briefing documents released Wednesday, the FDA and Zevra agreed to a reanalysis that removed measures of cognition, where there were concerns with the validity and reliability of the data.
But the agency also said it has “concerns regarding the validity of the primary endpoint,” and that “there is uncertainty regarding the strength of the evidence” from the pivotal study.
Zevra’s shares $ZVRA were up around 20% Wednesday. The newly formed Genetic Metabolic Diseases Advisory Committee will vote Friday on whether Zevra’s data support that arimoclomol is effective for treating the disease. The FDA isn’t required to follow the committee’s recommendation, but often does.
Another key point likely to be discussed Friday is the role of miglustat, a drug approved in the EU, Canada and Japan, but not in the US for Niemann-Pick disease. In the US, miglustat is marketed by Johnson & Johnson as Zavesca for certain Gaucher disease patients, but the drug is also used off-label to treat Niemann-Pick disease type C. “The briefing docs seem positive on combination use,” wrote William Blair analyst Tim Lugo Wednesday morning, noting that is “something to watch” for Friday.
In the pivotal clinical trial, Study NPC-002, 78% of patients were also receiving miglustat.
The regulatory agency also raised a series of concerns over the preclinical data describing arimoclomol’s effects, both in cell and mouse studies, and questioned the preclinical data around the drug’s proposed mechanism of action.
“Beyond the data discussions, we expect significant patient advocacy at the meeting in support of approval,” Lugo wrote.
Arimoclomol was previously being developed by Orphazyme — a Danish neurodegenerative disease biotech that was a “meme stock” before the 2021 FDA rejection. Zevra acquired Orphazyme and the drug in 2022, and conducted additional nonclinical studies and reanalyzed the pivotal clinical trial results before resubmitting to the FDA.
The FDA has until Sept. 21 to rule on the drug.