Drug name
Last update: Aug 2026Rilpivirine Prodrug Nanoformulation (NM3RPV)
Developer(s)
Drug information
Not provided
NM3RPV
Not provided
Small molecule
prodrug of rilpivirine (non-nucleoside reverse transcriptase inhibitor (NNRTI))
NM3RPV is a prodrug nanoformulation of the non-nucleoside reverse transcriptase inhibitor (NNRTI) Rilpivirine. Currently in preclinical development, NM3RPV was manufactured as a long-acting nanoparticle version of myristoylated RPV (M3RPV) to prolong the apparent half-life and improve tissue distribution. In murine studies, NM3RPV generated RPV plasma concentrations above the protein-adjusted 90% inhibitory concentration (PA-IC90) (12 ng/mL) for 25 weeks with significant tissue distribution after a single intramuscular (IM) injection. In contrast, the same treatment (45 mg/kg RPV-eq.) in rhesus macaques resulted in low levels of active RPV, which quickly fell below the PA-IC90. The differences in metabolism may be due to lack of abundant carboxylesterases observed in primate blood plasma.
NM3RPV is in preclinical development and not currently approved.
Unknown
Therapeutic area(s)
- HIV
- Treatment
Administration route
Intramuscular
Associated long-acting platforms
Aqueous drug particle suspension
Use of drug
- Administered by a nurse
- To be determined
- Other/Variable/Unknown : Not yet available
- Every 3 months
Dosage
Not yet available
Not yet available
Not yet available
Not provided
Not provided
Associated compounds, formulations and regimens
Associated technologies
Not provided
Additional information
Developer(s)
University of Nebraska Medical Center
The University of Nebraska Medical Center (UNMC) is a renowned public academic health science center located in Omaha, Nebraska. Established in 1881, UNMC is a leading institution in fields such as cancer research, infectious diseases, and rural health. The university is dedicated to advancing health care through innovative research, education, and patient care.
Exavir Therapeutics
Exavir Therapeutics is a biopharmaceutical company focused on developing ultra-long-acting therapeutics for chronic viral infections and CNS disorders. Headquartered in San Francisco, CA, they utilize prodrug nano-formulation technology to extend the half-life of drugs. Their current research focus primarily targets HIV, with the goal of improving treatment adherence and patient outcomes.
Drug structure
Scale-up and manufacturing prospects
The NM3RPV formulation is in preclinical development and has only been produced at small-scale for research use.
Avestin EmulsiFlex-C3 high-pressure homogenizer, rotary evaporator, silica column chromatography. RPV and M3RPV samples were separated on a Phenomenex Kinetex 5 μm C18 column (150 × 4.6 mm) (Torrance, CA).
Nanoformulations of RPV and M3RPV (NRPV and NM3RPV, respectively) were manufactured using an Avestin EmulsiFlex-C3 high-pressure homogenizer (Ottawa, ON, Canada). NRPV was prepared to best replicate RPV LA developed by Janssen. Specifically, 1% (w/v) P338 was dispersed in H2O, followed by the addition of 10% (w/v) RPV-free base and mixing overnight. Similarly, NM3RPV contained 2.1% P407 and 21% M3RPV in H2O. Formulations were homogenized at 20,000 psi to generate homogeneous nanocrystals of uniform size and polydispersity.
Nanoparticle physicochemical characterization for size (nm), PDI and zeta potential (mV) were evaluated by dynamic light scattering (DLS, Malvern Zetasizer Nano-ZS, Worcestershire, UK). NM3RPV and NRPV drug quantitation was conducted by UPLC-UV/Vis. Drug quantitation was performed on a Waters ACQUITY ultra-performance liquid chromatography (UPLC) H-Class system with TUV detector and Empower 3 software (Milford, MA).
Excipients & delivery device(s)
Not provided
The novel excipient poloxamer 338 (P338) is used in the final RPV (NM3RPV) formulation. Following both an in-vitro mammalian chromosome aberration and an Ames test, it was considered to be non-genotoxic with no evidence for mutagenicity. Further P338 fertility, genotoxicity and development studies have been conducted with no negative effects, in addition to a 6-week and 9-month minipig repeat-dose toxicity study. No adverse local or systemic toxicity was reported in the minipigs at 100mg/month (Margin of Exposure:19).
Not provided
No delivery device
Safety, Efficacy and Evidence Summary
Not provided
Not provided
Not provided
Not provided
Lipid nanoparticle comprising rilpivirine and at least one PEGylated lipid and a CCR5 targeting moiety and use thereof to treat HIV-1
The present invention provides lipid nanoparticles and methods of use thereof.
WO2025030072
Formulation
BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA
Not provided
August 2, 2044
National phase not entered yet; deadline for entry 02.02.2026
Prodrug compound of rilpivirine, crystaline nanoparticle of said prodrug, and use thereof to treat HIV (MRPV14 compound in claim 11)
The present invention provides prodrugs and methods of use thereof.
WO2019199756
Compound
BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA
Not provided
April 9, 2039
Granted: US Pending: CA Not in force: EP