Optimized production process leads to new FDA-approved treatment for fungal infections
2022
Challenge
In 2018, IRP researchers collaborated with Viamet Pharmaceuticals to develop a novel class of drugs to treat fungal infections, beginning with cryptococcal meningitis (CM). However, Viamet’s manufacturing process was unsuitable for producing the amount of the drug needed to treat patients around the world. The process included the use of a potentially explosive chemical, required extensive rounds of purification and separation, and generated a non-crystalline final material that made it difficult to study the drug’s effectiveness and behavior in the body. The process was also too costly to support development of a therapy to treat an infectious disease like CM that predominantly affects people in countries with few economic resources.
Advance
The IRP team redesigned the manufacturing process to produce the CM treatment, then known as VT-1129. The team evaluated 12 approaches, which led to three practical solutions to safely generate VT-1129 in a purer, more stable, and more easily testable form. In addition, the final material does not require inefficient chromatographic purifications and separations. Finally, cost analysis identified the most economical of these routes to substantially lower the overall production costs. NIH and Viamet subsequently filed six joint patent applications related to the synthesis of VT-1129 and related molecules, which were all licensed to Viamet. From these six applications, several US and foreign patents have been granted.
Impact
The IRP-designed production process allowed Viamet to begin clinical evaluation of VT-1129 as a treatment for CM. Viamet also leveraged the same manufacturing process to advance a related drug, VT-1161, into clinical trials as a treatment for recurrent yeast infections. Mycovia Pharmaceuticals acquired Viamet in 2018 and brought VT-1161 to market under the name Vivjoa in 2022 after its approval by the U.S. Food and Drug Administration (FDA). Mycovia continues to develop additional compounds to treat a range of rare and common fungal infections, all relying upon the manufacturing process created by the IRP scientists.
Publications
Wiederhold NP, Xu X, Wang A, Najvar LK, Garvey EP, Ottinger EA, Alimardanov A, Cradock J, Behnke M, Hoekstra WJ, Brand SR, Schotzinger RJ, Jaramillo R, Olivo M, Kirkpatrick WR, Patterson TF. (2018). In vivo efficacy of VT-1129 against experimental cryptococcal meningitis with the use of a loading dose-maintenance dose administration strategy. Antimicrob Agents Chemother. 62(11):e01315-18. doi: 10.1128/AAC.01315-18.
Wiederhold NP, Najvar LK, Garvey EP, Brand SR, Xu X, Ottinger EA, Alimardanov A, Cradock J, Behnke M Hoekstra WJ, Schotzinger RJ, Jaramillo R, Olivo M, Kirkpatrick WR, Patterson TR. (2018). The fungal Cyp51 inhibitor VT-1129 is efficacious in an experimental model of cryptococcal meningitis. Antimicrob Agents Chemother. 62(9):e01071-18. doi: 10.1128/AAC.01071-18.
This page was last updated on Friday, November 24, 2023