Drug-device glitches prompt FDA to turn back Evoke Pharma's Gimoti nasal spray

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The complete response letter cites issues in the device's quality control as well as clinical pharmacology data. No safety issues were raised, and the agency did not request additional studies, according to Evoke Pharma. (FDA)

The FDA has rebuffed Evoke Pharma’s nasal spray Gimoti, a version of the decades-old oral drug metoclopramide, on worries the spray device isn't delivering "reproducible" dosing, a company executive said Tuesday.

Gimoti is designed to deliver metoclopramide faster than pills do, offering quick relief for diabetic women whose stomachs are too slow to move food to the intestines, a condition called gastroparesis.

The FDA’s complete response letter isn't a complete surprise. In it, the company raised questions that track with concerns raised by its reviewers last month. Still, the news sent Evoke’s stock price down at least 40% in premarket trading.

That March multidisciplinary review letter cited three sections of the company’s new drug application, according to Evoke: chemistry and quality control related to the commercially available spray device used in the combination product; a lack of clinical information to support differences in sex-based efficacy; and the drug’s maximum concentration data not being within the parameters for bioequivalence.

The CRL follows up on only two of those issues, namely the drug/device product quality and the clinical pharmacology data. No safety issues were raised by the FDA, and the agency did not request any additional clinical studies, the Solana Beach, California-based company said.

“We believe that the issues cited in the CRL, which were related to concerns over reproducible dose delivery, can be addressed,” Evoke President and CEO Dave Gonyer said in a statement. “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.”

RELATED: Evoke fails out of Phase III, falling 75%

Gimoti previously stumbled in a phase 3 trial in July 2016, missing its primary endpoint in what the company described as “an anomaly.” While topline data showed the majority of the study’s clinical sites returned statistically significant benefits with the drug, the remaining 13 out of 41 sites instead showed statistically significant benefits for placebo.

According to Evoke, the clinical pharmacology issues cited in the CRL were related to low concentrations in a group of study participants that represented less than 5% of the doses administered  in a pharmacokinetics study, driving down the overall average of the data.

In the CRL, the FDA recommended a root cause analysis to determine the origin of the PK variability, as well as strategies to mitigate the issue. The FDA also requested additional data from registration batches of the manufactured combination product to better measure the nasal spray’s droplet size distribution in the resubmission of the company’s 505(b)(2) NDA.

RELATED: Evoke Pharma's nasal spray outdoes oral generic for diabetes-related stomach disease

Evoke says that if approved, Gimoti would be the first non-oral drug treatment for acute and recurrent gastroparesis and the first treatment advance in 40 years. With symptoms including flares of nausea and vomiting as well as delays in emptying of the stomach into the intestines, treating with an oral drug can be ineffective at times.

In preparation this past January, Evoke signed a commercialization partnership with Novos Growth Partners, which would provide a $5 million credit line after FDA approval.

Under the five-year deal, Evoke maintains ownership of the NDA as well as legal and manufacturing responsibilities, while Novos would provide the working capital to fund the launch. Evoke would also retain a contract sales organization managed by Novos. Once sales surpass commercialization costs, Novos would receive a percentage of sales as a service fee, with Evoke keeping more than 80% of the profits.

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