Depulfavirine nanosphere LAI

Associated long-acting platforms

nanosphere

Administration route

Intramuscular

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

No delivery device

Scale-up prospects

Not provided

Tentative equipment list for manufacturing

1. Rotary jar mill (U.S. Stoneware 700 Series Jar Mill) 2. Grinding jars (milling jars) 3. Zirconia grinding media (Zircon Sand) - 0.5 mm YTZ® Zirconia grinding and dispersion media 4. Refrigerated storage 5. Filtration apparatus 6. Particle size analyzer (Malvern Zetasizer Nano ZS)

Manufacturing

Manufacturing process and considerations: 1. Aqueous solution containing poloxamer + saccharide 2. Add Crystalline Depulfavirine in the aqueous phase 3. Wet Nanomelling with zirconia for 24 h at ~104 rpm 3. Settling: 16–20 h at 2–8 °C 4. Lyophilisation of nanosuspension forming stable dry nanospore cake 5. Filtration to remove grinding media 5. Freeze drying and reconstitution

Specific analytical instrument required for characterization of formulation

1. HPLC–MS/MS System

HIV-VM1500ALAI-03

Identifier

NCT05204394

Link

https://clinicaltrials.gov/study/NCT05204394

Phase

Phase II/III

Status

Unknown status

Sponsor

Viriom

More details

Multicenter, open-label, randomized, active control study to evaluate efficacy and safety of switching to VM-1500A-LAI + 2NRTIs from the 1st line standard of care therapy for 48 weeks. The 1st part of the study will select one of 2 dose cohorts: 600mg or 900mg.

Purpose

Study to Evaluate Efficacy and Safety of Switching to VM-1500A-LAI + 2NRTIs From the 1st Line Standard of Care Therapy

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2022-04-01

Actual Start Date
Not provided

Anticipated Date of Last Follow-up
2022-01-21

Estimated Primary Completion Date
2023-09-30

Estimated Completion Date
2023-10-16

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. Signed Patient Information Sheet and Informed Consent Form 2. Men and women aged 18 or older at the time of signing the informed consent; 3. HIV-1 infection confirmed serologically by ELISA or immunoblot analysis (or documented HIV-1 infection); 4. Stable doses of standard-of-care antiretroviral therapy (NNRTI + 2NRTI) for at least 6 months prior screening; 5. Serological confirmation of adequate virological suppression within 6 and 12 months before screening as documented by : * HIV-1 RNA plasma level \< 50 copies/ml at screening; * СD4+ Т-cells count ≥ 200 cells/mm3 at screening; 6. Adequate organ function as documented by laboratory test results; 7. Female patients must be postmenopausal not less than 2 years, surgically sterile, or if of child-bearing pot

Health status

Study type

Interventional (clinical trial)

Enrollment

438

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

HIV-VM1500ALAI-02

Identifier

NCT05163535

Link

https://clinicaltrials.gov/study/NCT05163535

Phase

Phase I/II

Status

Completed

Sponsor

Viriom

More details

Open labelled, randomized study to evaluate the efficacy, safety and dose selection of VM-1500A-LAI drug in HIV-infected patients transferred from previous stable therapy (NNRTI + 2NRTI), including ELPIDA®.

Purpose

Open Labelled, Randomized Study to Evaluate the Efficacy, Safety and Dose Selection of VM-1500A-LAI Drug in HIV-infected Patients Transferred From Previous Stable Therapy (NNRTI + 2NRTI), Including EL

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2021-01-19

Anticipated Date of Last Follow-up
2022-01-10

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2021-08-03

Actual Completion Date
2021-08-03

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. Signed Patient Information Sheet and Informed Consent Form 2. Men and women aged 18 and over; 3. HIV-1 infection confirmed serologically by ELISA or immunoblot analysis (or documented HIV-1 infection); 4. Clinically stable HIV infection (clinical stages 1 or 2 according to the WHO classification, Appendix 1) 5. Stable doses of NNRTIs (ELPIDA®, 20 mg capsules) + 2NRTIs for 6 months before screening; 6. HIV-1 RNA plasma level ≤ 50 copies/ml at screening; 7. СD4+ Т-cells count ≥ 200 cells/mm3 at screening; 8. Laboratory parameters; 9. The patients' consent to use adequate contraception methods during the study (condom with spermicide). Exclusion Criteria: 1. Presence of known primary HIV-1 resistance to ART. Viral resistance mutations are defined as any basic mutatio

Health status

Study type

Interventional (clinical trial)

Enrollment

36

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

HIV-VM1500ALAI-01

Identifier

NCT03706911

Link

https://clinicaltrials.gov/study/NCT03706911

Phase

Phase I

Status

Completed

Sponsor

Viriom

More details

To evaluate safety and tolerability of VM-1500A-LAI after its single and multiple intramuscular ascending dose to healthy volunteers

Purpose

Study to Evaluate Safety, Tolerability and Pharmacokinetics of VM-1500A-LAI Single and Multiple Ascending Doses in Healthy Subjects

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-01-21

Anticipated Date of Last Follow-up
2021-12-06

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2020-03-27

Actual Completion Date
2020-05-18

Studied populations

Age Cohort

• Adults

Genders

• Male

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: 1. Non-smoking healthy male subjects aged 18 - 45 years (inclusive); 2. Verified "healthy" status, based on standard clinical, laboratory, and instrumental examination methods; 3. Body weight ≥ 50 kg and Body Mass Index in the range from 18.5 to 30.0 kg/m2; 4. Signed the Participant Explanation Sheet and the Informed Consent Form; 5. Consent to use an adequate method of contraception throughout the study and 3 months after its completion: a condom with spermicide substance (cream, foam or suppository). Exclusion Criteria: 1. Chronic cardiovascular, bronchopulmonary, neuroendocrine, musculoskeletal or gastrointestinal diseases, as well as immunologic, hepatic, renal, or blood diseases; 2. Laboratory abnormalities, or ECG abnormalities at Screening; 3. Systolic arteria

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

27

Allocation

Randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

Proprietary excipients used

Not provided

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

1. Poloxamer P338 2. Mannitol or saccharose 3. Phosphate buffered saline (PBS), water for injection

Residual solvents used

Not provided

Description

PHARMACEUTICAL NANOSUSPENSION FOR THE THERAPY OF HIV INFECTION

Brief description

The present invention relates to a pharmaceutical composition (nanosuspension) for a long-acting injectable (LAI) drug for the long-term maintenance therapy of HIV/AIDS. A pharmaceutical nanosuspension for use as an injectable drug for the long-term maintenance therapy of HIV infection is claimed, comprising a composition that contains, as an active ingredient, a compound of general formula 1 in crystalline or polycrystalline form, in which R is C2H5CON-Na+, NH2.

Representative patent

EP3643304A1

Category

Not provided

Patent holder

VIRIOM INC

Exclusivity

Not provided

Expiration date

February 14, 2038

Status

Anticipated expiration

Description

Substituted 3,4,12,12a-Tetrahydro-1H-[1,4]Oxazino[3,4-c]Pyrido[2,1-f][1,2,4]Triazine-6,8-dione, Pharmaceutical Composition, Method for the Production and Use Thereof

Brief description

Substituted 3,4,12,12a-tetrahydro-1H-[1,4]-oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione of general formula 1, its stereoisomer, their prodrug, pharmaceutically acceptable salt, solvate, hydrate, and a crystalline or polycrystalline form thereofwhere:R1 is diphenylmethyl, bis(4-fluorophenyl)methyl, (3,4-difluorophenyl)(phenyl)methyl, (3,4-difluorophenyl)(2-methylsulfanylphenyl)methyl;R2 is hydrogen or a {[(C1-C3alkyl)oxycarbonyl]-oxy}methoxy and stereoisomers thereof.

Representative patent

US20240383919A1

Category

Not provided

Patent holder

Viriom Inc

Exclusivity

Not provided

Expiration date

Not provided

Status

Pending

Publications

Snyder, A. A., Kaufman, I. L., Risener, C. J., Kirby, K. A., & Sarafianos, S. G. (2026). HIV-1 Reverse Transcriptase interactions with Long-acting NNRTI, Depulfavirine (VM1500A). bioRxiv, 2026-04. doi: https://doi.org/10.64898/2026.04.06.715899

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key components of combination antiretroviral therapy (ART) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection, binding an allosteric pocket of reverse transcriptase (RT) and inhibiting viral replication. Although second-generation NNRTIs have improved potency and resistance profiles compared to first-generation NNRTIs, the continued emergence of resistant viral strains and the need for long-acting therapeutic options underscore the importance of developing next-generation compounds. Depulfavirine (VM1500A) is a potent NNRTI being developed as a long-acting formulation. Its prodrug, elsulfavirine (ESV), is approved for HIV-1 treatment in Eurasian countries as a once-daily oral regimen and has demonstrated favorable antiviral efficacy, pharmacokinetics, and tolerability in clinical studies. Here, we report the 2.4 Å crystal structure of HIV-1 RT in complex with depulfavirine, revealing an extended binding conformation within the NNRTI pocket that reaches from the back of the binding pocket to the entrance. These interactions may shed light on mechanisms of resistance to the F227C mutation, with and without V106 substitution, and Y188L. Notably, depulfavirine maintains potent inhibition of common NNRTI-resistant RT variants, including K103N and Y181C. Combination studies of ESV with antivirals from diverse inhibitor categories demonstrated additive or near-synergistic activity with islatravir (ISL), cabotegravir (CAB), lenacapavir (LEN), and tenofovir (TDF). These findings highlight the broad resistance profile and potential of the depulfavirine combination.

Additional documents

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