After Letter to Commissioner, FDA Finally Gives Vanda Reason for Rejection, Chance for Hearing

 

After a series of strongly worded letters—one of which was addressed directly to Commissioner Robert Califf—the FDA has publicly laid out its reasoning for rejecting Vanda Pharmaceuticals’ gastroparesis drug candidate tradipitant.

In a notice posted on the Federal Register on Wednesday, the FDA finally provided a justification for declining to approve Vanda Pharmaceuticals’ gastroparesis candidate tradipitant last year—and offered the biotech a chance to request a hearing regarding the rejection.

The FDA’s explanation—a rarity for the regulator—comes just days after Vanda wrote to Agency Commissioner Robert Califf, criticizing the federal body for “unacceptable” delays in its decisions and responses. Vanda put much of the blame on Califf, who according to the biotech had allowed a “culture of obfuscation and closemindedness to fester at FDA.”

Tradipitant is a small molecule blocker of the neurokinin-1 receptors, which are typically specifically expressed in the gastrointestinal tract and in regions of the brain involved in the vomit reflex. The FDA issued its Complete Response Letter for tradipitant in September 2024, though at the time, Vanda claimed that the regulator did not present its reasoning for the rejection.

Vanda bristled at the regulatory rebuff and quickly issued a scathing assessment of the FDA, claiming that the decision “generally disregarded the evidence provided.” The biotech also blasted the timing of the verdict, which according to Vanda came past the mandated 180-day review period under the Federal Drug and Cosmetic Act.

In its notice on Wednesday, the regulator laid out several deficiencies with Vanda’s application for tradipitant. One of the biotech’s Phase III studies, for instance, “did not demonstrate a statistically significant” effect of tradipitant versus placebo at improving nausea severity in gastroparesis patients.

In this late-stage trial, Vanda’s candidate likewise failed to best placebo in terms of other signs and symptoms of gastroparesis. “The estimated difference between tradipitant and placebo for these endpoints was generally close to zero, except for the nausea-free days endpoint, which numerically favored placebo at Week 12,” the regulator pointed out.

Vanda also backed tradipitant’s application with data from a Phase II trial that, the FDA conceded on Wednesday, demonstrated a significant improvement in individual daily nausea severity scores after treatment with the experimental drug. However, the regulator pointed out that these results “were not persuasive” due to “methodological shortcomings . . . that could bias results.”

The agency did not detail these shortcomings, only noting that Vanda’s statistical adjustments to account for these concerns “were not robust with respect to missing data assumptions.”

Taken together, tradipitant’s data package failed to “demonstrate substantial evidence of effectiveness on its own,” the FDA wrote.

As for safety, the regulator likewise called Vanda’s data “inadequate” to establish the safety of using tradipitant for gastroparesis, a chronic condition that typically requires ongoing or recurrent medication. “Additional longer-term safety data are needed, in part, to inform the safe use of the drug” in this indication, according to the FDA.

https://www.biospace.com/fda/after-letter-to-commissioner-fda-finally-gives-vanda-reason-for-rejection-chance-for-hearing