Development of a once-weekly oral Doxycycline for malaria prophylaxis

Currently, the malaria prevention drug regimens prescribed by the U.S. military require personnel to take a pill every day and are frequently ineffective because of poor compliance. It is anticipated that the successful development of the once-weekly product will have an immediate impact on enhancing military readiness for Forces deployed in malaria-endemic regions as well as civilian populations such as travelers, diplomatic personnel, and international aid workers. The technology could also see applications with other drugs where patient compliance could benefit from a once-weekly dosing regimen. Malaria remains a difficult worldwide challenge and is the single largest disease, non-battle injury threat for U.S. troops deployed to malaria-endemic regions. Safe and effective prophylactic anti-malarial drugs are a critical countermeasure against malaria infection that serve as a complement to personal protective measures. Successful prevention of malaria is highly dependent on compliance with the current prescribed daily chemoprophylaxis regimen. However, maintaining drug compliance by U.S. Service members can be difficult due to the inconvenience of a daily oral dosing requirement, associated side effects (such as nausea and photosensitivity), organizational culture, command emphasis, and the demands of the operational environment. It is believed that a dosage form that allows once-weekly dosing for malaria prevention will be more effective than the once-daily medication because people will be more likely to take it as directed. This would be of tremendous benefit to U.S. Forces and civilian populations such as diplomatic personnel, international aid workers, and travelers. This project seeks to build upon previous work on a new technology for oral long-acting drug delivery. It is based on a dosage form that is swallowed in a capsule and releases drug steadily while residing in the stomach for at least one week. Gastric processes slowly break down the dosage form and remove it from the stomach after all of the drug has been released. The dosage form has been shown to be safe in animal models, with no signs of interference with digestion or damage to the interior of the stomach. Products using this technology are being developed for treatment of diseases where patients often fail to take their daily medications, such as Alzheimer’s disease, schizophrenia, and substance use disorder. Early human testing of the new dosage form is in progress. The drug chosen for this project is doxycycline, one of two first-line options for malaria prophylaxis in U.S. Forces deployed to malaria-endemic regions. As a daily-dosed drug with strict adherence requirements for protection and known gastrointestinal and photosensitivity side effects, Soldier compliance is of particular concern. The proposed project includes development of a formulation for a doxycycline-containing dosage form that releases doxycycline at a steady rate for a week to 10 days while residing in the stomach. Once the exact ingredients and manufacturing process have been determined, we will test the ability of the once-weekly doxycycline dosage form to prevent malaria in animal studies. If these studies are successful, more studies will be performed to ensure that the product is safe for human use and then submit an application to the U.S. Food and Drug Administration (FDA) seeking permission to perform a first-in-human clinical trial. The proposed program is a collaboration between Lyndra, Walter Reed Army Institute of Research (WRAIR) and Armed Forces Research Institute of Medical Sciences (AFRIMS). Lyndra is a clinical stage company that is developing the once-weekly dosage form technology, and WRAIR and its subordinate command AFRIMS are world leaders in tropical disease research and development.

Drug-based Strategies
Product Development

Sep 2019 — Sep 2023

$3.81M

United States