FDA Officials Reject NDA, in Current Form, for Gastroparesis Treatment
If approved, Gimoti would be the first non-oral drug treatment for symptoms associated with acute and recurrent diabetic gastroparesis in adult women and would represent the first significant advancement in the treatment of gastroparesis in 40 years.
Officials with the FDA have said they will not issue a new drug application (NDA) for the recurrent diabetic gastroparesis medication Gimoti in the application's present form, but they have issued recommendations to address the 2 remaining approvability issues, related to clinical pharmacoogy and product quality, in the NDA resubmission. The Agency did not request any new clinical data and did not raise any safety concerns.
In a prepared statement from the drug's manufacturer, Evoke Pharma, it was noted that the clinical pharmacology issue was specific to a low Cmax in patients representing less than 5% of the total administered Gimoti doses in the pivotal pharmacokinetic (PK) study. The Agency stated the overall lower mean Cmax was driven by the data from these few subjects. Without the aberrant doses, the statement reads, "the Company’s analysis shows the data met the bioequivalence criteria for both men and women." The Agency recommended a root cause analysis to determine the origin of the PK variability and mitigation strategies to address the issue.
Additionally, FDA officials requested data from previously planned registration batches of commercial product to be manufactured by the Company. These data were requested to provide additional support for the proposed acceptance criteria for droplet size distribution after actuation of the sprayer device.
“We believe that the issues cited in the [FDA's complete response letter], which were related to concerns over reproducible dose delivery, can be addressed. We look forward to meeting with FDA to gain a full understanding of the Agency’s requirements for approval and remain committed to bringing our novel nasal formulation of metoclopramide to patients,” Dave Gonyer, Evoke Pharma's President and CEO noted in the statement.
Gastroparesis is an episodic condition that disproportionately affects adult women and is characterized by slow or delayed gastric emptying of the stomach’s contents after meals, often resulting in flares of symptoms that include nausea, vomiting, abdominal pain and bloating. Vomiting and gastric emptying delays can cause unpredictable absorption of food and oral medications, which complicate glucose control and can lead to dehydration and malnutrition. These clinical manifestations of gastroparesis also potentially render existing oral drug treatment options ineffective. If approved, Gimoti would be the first non-oral drug treatment for symptoms associated with acute and recurrent diabetic gastroparesis in adult women and would represent the first significant advancement in the treatment of gastroparesis in 40 years.