CLINICAL TRIALS PROFILE FOR DORAVIRINE; LAMIVUDINE; TENOFOVIR DISOPROXIL FUMARATE

All Clinical Trials for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02397096 ↗	Safety and Efficacy of a Switch to Doravirine, Tenofovir, Lamivudine (MK-1439A) in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcrip	Active, not recruiting	Merck Sharp & Dohme Corp.	Phase 3	2015-06-09	The multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to MK-1439A (MK-1439 [doravirine] plus lamivudine and tenofovir disoproxil fumarate) in HIV-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) <50 copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.
NCT02403674 ↗	Comparison of Doravirine, Tenofovir, Lamivudine (MK-1439A) and ATRIPLA™ in Treatment-Naive Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439A-021)	Active, not recruiting	Merck Sharp & Dohme Corp.	Phase 3	2015-06-05	The purpose of this study is to compare the antiretroviral activity of doravirine, tenofovir, lamivudine (MK-1439A), a single-tablet, once-daily (q.d.) fixed-dose combination (FDC) containing doravirine (MK-1439) 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, with ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg, in treatment-naive participants infected with human immunodeficiency virus (HIV). The primary hypothesis is that doravirine, tenofovir, lamivudine q.d. is non-inferior to ATRIPLA™ q.d. as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48. This study has a total duration of 192 weeks, including a 96-week double-blind period and a 96-week open-label period. The present results are based on the first 48 weeks of this ongoing study.
NCT02629822 ↗	Safety and Efficacy of Doravirine, Tenofovir, Lamivudine (MK-1439A) in Participants Infected With Treatment-Naïve Human Immunodeficiency Virus (HIV) -1 With Transmitted Resistance (MK-1439A-030)	Completed	Merck Sharp & Dohme Corp.	Phase 2	2016-01-14	The primary objectives of this study are to evaluate the antiretroviral activity and the safety/tolerability of open-label doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF; MK-1439A; DELSTRIGO™) consisting of a single fixed-dose combination (FDC) tablet of DOR/3TC/TDF 100 mg/300 mg/300 mg in treatment-naïve HIV-1 infected participants with select non-nucleoside reverse transcriptase inhibitor (NNRTI) transmitted resistance-associated mutations.
NCT03332095 ↗	Evaluating the Pharmacokinetics, Safety, and Tolerability of Doravirine (MK-1439) and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (MK-1439A) in HIV-1-Infected Children and Adolescents	Active, not recruiting	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1/Phase 2	2018-03-21	The purpose of this study is to evaluate the pharmacokinetics, safety, and tolerability of doravirine (also called MK-1439 or DOR) and doravirine/lamivudine/tenofovir disoproxil fumarate (also called MK-1439A or DOR/3TC/TDF) in HIV-1-infected children and adolescents.
NCT04097925 ↗	Doravirine Concentrations and Antiviral Activity in Genital Fluids in HIV-1 Infected Individuals	Recruiting	Hospital Universitari de Bellvitge	Phase 2	2020-02-18	This study aims to evaluate the ability of Doravirine to penetrate the genital tract and suppress viral replication and provide evidence for the use of Doravirine as part of treatment strategies as prevention.

Clinical Trial Conditions for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate

Condition Name

Condition Name for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate
Intervention	Trials
HIV-1-infection	3
Hiv	3
HIV Infections	2
HIV-1 Infection	2

Condition MeSH

Condition MeSH for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate
Intervention	Trials
HIV Infections	6
Acquired Immunodeficiency Syndrome	4
Immunologic Deficiency Syndromes	2
Body Weight	2

Clinical Trial Locations for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate

Trials by Country

Trials by Country for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate
Location	Trials
United States	29
South Africa	7
Spain	5
Russian Federation	5
France	4

Trials by US State

Trials by US State for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate
Location	Trials
Colorado	3
New Jersey	2
Maryland	2
Illinois	2
Florida	2

Clinical Trial Progress for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate

Clinical Trial Phase

Clinical Trial Phase for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	5
Phase 2	3

Clinical Trial Status

Clinical Trial Status for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate
Clinical Trial Phase	Trials
Recruiting	5
Not yet recruiting	3
Active, not recruiting	3

Clinical Trial Sponsors for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate

Sponsor Name

Sponsor Name for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate
Sponsor	Trials
Merck Sharp & Dohme Corp.	5
Professor Francois Venter	2
Willem Daniel Francois Venter	2

Sponsor Type

Sponsor Type for Doravirine; Lamivudine; Tenofovir Disoproxil Fumarate
Sponsor	Trials
Other	14
Industry	7
NIH	1

Doravirine, Lamivudine, and Tenofovir Disoproxil Fumarate: Clinical Trials, Market Analysis, and Projections

Introduction

The combination of doravirine, lamivudine, and tenofovir disoproxil fumarate, marketed as Delstrigo, represents a significant advancement in the treatment of HIV. This single-tablet regimen (STR) has undergone extensive clinical trials and has been approved by regulatory bodies such as the US FDA. Here, we delve into the clinical trials, market analysis, and future projections for this drug combination.

Clinical Trials Overview

DRIVE-FORWARD and DRIVE-AHEAD Trials

The approval of Delstrigo was based on the findings from two pivotal Phase 3 clinical trials: DRIVE-FORWARD and DRIVE-AHEAD.

• DRIVE-FORWARD: This trial involved 766 HIV-positive participants with no prior treatment experience. Participants were randomly assigned to receive either doravirine or boosted darunavir, each in combination with tenofovir DF/emtricitabine or abacavir/lamivudine. After 48 weeks, 84% of participants taking doravirine and 80% of those taking boosted darunavir had undetectable viral loads, demonstrating the non-inferiority of doravirine[4].

• DRIVE-AHEAD: This trial included 728 previously untreated participants who were randomized to receive either the fixed-dose combination of doravirine, tenofovir DF, and lamivudine (Delstrigo) or a single-tablet regimen containing efavirenz, tenofovir DF, and emtricitabine (Atripla). At 48 weeks, 84% of participants on Delstrigo and 81% on Atripla had undetectable viral loads, again showing non-inferiority of doravirine[4].

Safety and Tolerability

Both trials highlighted the safety and tolerability of Delstrigo. In DRIVE-FORWARD, only 2% of doravirine recipients stopped treatment due to adverse events, compared to 3% of those taking boosted darunavir. In DRIVE-AHEAD, Delstrigo recipients were about half as likely as Atripla recipients to discontinue treatment due to adverse events (3% vs 7%)[4].

Common Side Effects

The most common side effects associated with doravirine were headache, nausea, diarrhea, and nasopharyngitis. Notably, Delstrigo was associated with significantly fewer neuropsychiatric side effects compared to Atripla, such as dizziness, sleep problems, and altered cognition[4].

Market Analysis

Market Forecast

According to a GlobalData report, the combined sales of Delstrigo and its standalone component, Pifeltro (doravirine), are forecasted to reach approximately $500 million across the seven major markets (7MM) by 2023. Delstrigo is expected to see the most success, with peak 7MM annual sales projected at $369 million in 2023, while Pifeltro is forecasted to reach $144 million in 2025[5].

Competitive Landscape

The HIV market is highly competitive, with several single-tablet regimens available. However, Delstrigo's convenience as a fixed-dose combination therapy is expected to drive its success. Other notable STRs include ViiV Healthcare’s dolutegravir/lamivudine and Gilead’s bictegravir/emtricitabine/tenofovir alafenamide fumarate (TAF)[2].

Patient Preference

HIV patients often require complex treatment regimens, making adherence a significant challenge. Delstrigo's single-tablet formulation addresses this issue by providing a more convenient dosing regimen, which is likely to enhance patient compliance and overall treatment outcomes[5].

Pharmacokinetics and Bioequivalence

Bioequivalence Studies

The bioequivalence of the film-coated tablet version of Delstrigo with the clinical trial uncoated oral compressed tablet version was demonstrated in Study P039. The pharmacokinetic parameters of doravirine, lamivudine, and tenofovir disoproxil fumarate in the fixed-dose combination were found to be similar to those of the individual components[3].

Lack of Toxicological Interactions

Toxicological studies have shown no target organ of toxicity for doravirine, and no clinically significant interactions between doravirine and lamivudine/tenofovir disoproxil fumarate are expected. This supports the safety profile of the combination therapy[3].

Regulatory Approvals

FDA Approval

Delstrigo and Pifeltro were approved by the US FDA in 2018 for the treatment of HIV in adults who are starting antiretroviral therapy for the first time. Both drugs are taken once daily with or without food[4].

European Medicines Agency Review

Both products are also under review by the European Medicines Agency, indicating potential for broader market access in the future[4].

Future Projections

Ongoing and Future Studies

Doravirine is being tested in combination with other antiretrovirals, such as MK-8591, in ongoing clinical trials. These studies aim to further expand the treatment options and improve the efficacy and safety profiles of HIV therapies[4].

Market Growth

The global HIV market is expected to experience modest growth driven by the introduction of novel integrase inhibitors and protease inhibitors. Delstrigo, with its favorable safety and efficacy profile, is well-positioned to capture a significant share of this growing market[2].

Key Takeaways

• Clinical Efficacy: Delstrigo has demonstrated non-inferiority to other established HIV treatments in clinical trials.
• Safety and Tolerability: The combination has shown a favorable safety profile with fewer adverse events compared to some other treatments.
• Market Forecast: Delstrigo is expected to achieve significant sales, driven by its convenience and patient preference.
• Regulatory Approvals: Approved by the US FDA and under review by the European Medicines Agency.
• Future Studies: Ongoing trials aim to further enhance the treatment options and efficacy of doravirine-based regimens.

FAQs

What are the key components of Delstrigo?

Delstrigo is a single-tablet regimen that combines doravirine, lamivudine, and tenofovir disoproxil fumarate.

What were the outcomes of the DRIVE-FORWARD and DRIVE-AHEAD trials?

Both trials showed that Delstrigo was non-inferior to other established HIV treatments, with high rates of viral suppression and favorable safety profiles.

What are the common side effects associated with Delstrigo?

Common side effects include headache, nausea, diarrhea, and nasopharyngitis, with significantly fewer neuropsychiatric side effects compared to some other treatments.

What is the market forecast for Delstrigo?

Delstrigo is expected to achieve peak 7MM annual sales of $369 million by 2023, driven by its convenience and patient preference.

Is Delstrigo approved for use in children and adolescents?

The tenofovir DF component in Delstrigo is currently being tested in children and adolescents, but it is not yet approved for this population.

Sources

1. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate for Nonoccupational HIV Postexposure Prophylaxis - Oxford Academic.
2. Global Drug Forecast and Market Analysis to 2025 - GlobalData.
3. Australian Public Assessment Report for Doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate - Therapeutic Goods Administration.
4. Two new doravirine pills approved in US - Aidsmap.
5. Merck should expect strong sales for two new HIV drugs, says GlobalData - Pharmaceutical Manufacturer.