FDA Rejects NK1R Antagonist for Gastroparesis

The FDA declined to approve tradipitant for adults with symptoms of gastroparesis, or delayed gastric emptying, drugmaker Vanda Pharmaceuticals announced on Thursday.

Support for the neurokinin-1 receptor (NK1R) antagonist included a negative phase III trial and a positive phase II study involving patients with diabetic or idiopathic gastroparesis, along with data from an open-label trial and expanded access program.

According to the company, the FDA’s complete response letter (CRL) “was conclusory in nature, generally disregarded the evidence provided and instead suggested that Vanda conduct additional studies with a design and duration inconsistent with the advice of key experts in the field and not appropriate based on the scientific understanding and natural course of the disorder.”

The company also dinged the agency for taking too long with its rejection, saying the FDA blew past the deadline for a decision required under the Food Drug and Cosmetic Act.

Gastroparesis, which is associated with severe nausea, has been in the news of late given its link to GLP-1 receptor agonists; the condition has sparked safety concerns for patients taking the diabetes or weight-loss drugs prior to surgery.

Tradipitant remains an investigational drug, but other agents in the NK1R antagonist class have been approved for treating chemotherapy-induced nausea and vomiting.

In the phase III study of tradipitant for gastroparesis, the drug failed to reduce severe nausea at 12 weeks, as measured by the Gastroparesis Core Symptom Daily Diary (GCSDD, a 0-5 scale), and didn’t demonstrate improvements in prespecified secondary endpoints. Post-hoc analyses that controlled for patients’ baseline severity inflation and use of rescue medications appeared to show a benefit, however.

The phase II trial, on the other hand, met its primary endpoint. From baseline to week 4, mean scores on the GCSDD dropped by 1.2 points with tradipitant versus a 0.7-point decline with placebo (P=0.0099). Patients on tradipitant also reported a greater increase in nausea-free days (28.8% vs 15% increase with placebo at week 4). There were no safety concerns, according to investigators, and most adverse events associated with the drug were mild or moderate in severity.

Tradipitant is also under investigation as a treatment for motion sickness.

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