FDA Issues CRL for Motion Sickness Drug

The FDA has issued a complete response letter (CRL) for Defender Pharmaceuticals’ new drug application (NDA) for intranasal scopolamine (DPI-386) to prevent nausea and vomiting induced by motion in adults. DPI-386 is a nasal gel. The company did not say what was at issue with the complete response letter, but Defender officials said in a press release they plan to meet with FDA to discuss next steps.

Oral scopolamine has a very poor bioavailability, according to the company. An intranasal version would allow for rapid vascular uptake and potentially direct absorption into the central nervous system.

The submission was based on a multi-study clinical development program, including phase 3 study of DPI-386. The phase 3 study enrolled 503 people who had a history of motion sickness. Participants were divided into eight groups for separate trips of varying sea conditions. This study found that intranasal scopolamine demonstrated a significantly lower incidence of vomiting or the need for rescue medication in comparison with individuals administered placebo. The data were presented at the 2023 Military Health System Research Symposium (MHSRS) in August 2023 in Kissimmee, Florida. The phase 3 study was funded in part by the U.S. Naval Medical Research Unit (NAMRU-D).

“Nausea and vomiting associated with motion remains a debilitating factor in military performance that is true regardless of mode of transportation and largely inescapable due to military personnel’s frequent inability to withdraw from the offending stimuli,” Barry I. Feinberg, M.D., president and CEO of Defender Pharmaceuticals, said in a press release.

Additionally, Defender announced in October 2023 that it is collaborating with the National Aeronautics and Space Administration (NASA) for two phase 2 studies to assess the ability of DPI-386 to mitigate G-transition induced motion sickness and enhance sensorimotor performance. The first study evaluates DPI-386 alone and in combination with sensory augmentation compared with placebo. The second study evaluates DPI-386 in operational field settings, with both astronaut and ground-control subjects, when exposed to preflight training exercises and simulations. Both trials are being led by primary investigator Scott J. Wood, Ph.D. of NASA, and Neuroscience Laboratory Principal Investigator.