CLINICAL TRIALS PROFILE FOR DORAVIRINE

All Clinical Trials for Doravirine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01466985 ↗	A Study of Doravirine (MK-1439) in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439-005)	Completed	Merck Sharp & Dohme Corp.	Phase 1	2011-10-21	This is a study to evaluate the safety, tolerability, pharmacokinetics, and antiretroviral activity of doravirine (MK-1439) as monotherapy in antiretroviral therapy (ART)-naïve, HIV-1-infected participants.
NCT01632345 ↗	A Dose-Ranging Study to Compare Doravirine (MK-1439) Plus TRUVADA® Versus Efavirenz Plus TRUVADA® in Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-1439-007)	Completed	Merck Sharp & Dohme Corp.	Phase 2	2012-10-12	The hypothesis tested in this study is that doravirine (MK-1439) at the final dose selected is superior to efavirenz, each given in combination with TRUVADA®, as measured by the percentage of participants with CNS events by Week 8. If superiority is established at Week 8, the same hypothesis will be tested for Week 24.
NCT02089659 ↗	A Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Doravirine (MK-1439) (MK-1439-019)	Completed	Merck Sharp & Dohme Corp.	Phase 1	2014-03-26	This study aimed to investigate the influence of hepatic insufficiency on the pharmacokinetics (PK) of doravirine (MK-1439). In Part 1, PK of doravirine in participants with moderate hepatic insufficiency was compared with that of healthy control subjects matched with regard to mean age and weight. If a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1, study Part 2 was to evaluate PK of doravirine in participants with mild hepatic insufficiency.
NCT02275780 ↗	Safety and Efficacy of Doravirine (MK-1439) in Participants With Human Immunodeficiency Virus 1 (HIV-1) (MK-1439-018)	Active, not recruiting	Merck Sharp & Dohme Corp.	Phase 3	2014-12-01	To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Eligible participants in either of the Base Study groups will continue to receive the doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1. Eligible participants who are deriving benefit will continue in Study Extension 2 to receive the doravirine-containing regimen open label until doravirine becomes locally available or for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine 100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48. If non-inferiority is established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir (800 mg/100 mg) q.d. will be assessed.
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.

Clinical Trial Conditions for Doravirine

Condition Name

Condition Name for Doravirine
Intervention	Trials
HIV-1 Infection	13
HIV Infections	9
HIV-1-infection	8
Hiv	7

Condition MeSH

Condition MeSH for Doravirine
Intervention	Trials
HIV Infections	19
Acquired Immunodeficiency Syndrome	11
Immunologic Deficiency Syndromes	6
Infections	6

Clinical Trial Locations for Doravirine

Trials by Country

Trials by Country for Doravirine
Location	Trials
United States	105
France	42
Russian Federation	23
Spain	22
South Africa	21

Trials by US State

Trials by US State for Doravirine
Location	Trials
District of Columbia	9
Texas	9
Florida	8
California	8
Illinois	7

Clinical Trial Progress for Doravirine

Clinical Trial Phase

Clinical Trial Phase for Doravirine
Clinical Trial Phase	Trials
Phase 4	12
Phase 3	18
Phase 2	8

Clinical Trial Status

Clinical Trial Status for Doravirine
Clinical Trial Phase	Trials
Recruiting	16
Not yet recruiting	14
Completed	10

Clinical Trial Sponsors for Doravirine

Sponsor Name

Sponsor Name for Doravirine
Sponsor	Trials
Merck Sharp & Dohme Corp.	25
Merck Sharp & Dohme LLC	8
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia	3

Sponsor Type

Sponsor Type for Doravirine
Sponsor	Trials
Other	46
Industry	36
NIH	2

Doravirine: Clinical Trials, Market Analysis, and Projections

Introduction to Doravirine

Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Merck for the treatment of HIV-1 infection. It has been approved in various forms, including as a single agent (PIFELTRO) and as part of a fixed-dose combination regimen (DELSTRIGO, which includes doravirine, lamivudine, and tenofovir disoproxil fumarate)[1][4].

Clinical Trials Update

Phase 3 Trials: Doravirine/Islatravir Regimen

Merck recently announced topline results from two pivotal Phase 3 trials evaluating the investigational once-daily, oral, two-drug, single-tablet regimen of doravirine/islatravir (DOR/ISL) in adults with virologically suppressed HIV-1 infection. These trials, MK-8591A-051 and MK-8591A-052, compared DOR/ISL to existing antiretroviral therapies.

• Efficacy: Both trials met the primary efficacy criterion, demonstrating that DOR/ISL was non-inferior to the baseline antiretroviral therapy (bART) and to the combination of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The success was measured by the percentage of participants with HIV-1 RNA levels ≥50 copies/mL at Week 48[1][4].
• Safety: The safety profiles of DOR/ISL were generally comparable to those of the comparator therapies in these trials[1][4].

Long-Term Efficacy and Safety

Additional data from an ongoing Phase 2b clinical trial presented at the European AIDS Clinical Society (EACS) conference showed that the combination of doravirine and islatravir maintained viral suppression through 144 weeks. This long-term data supports the potential of this two-drug regimen for HIV-1 treatment[3].

Market Analysis

Current Market Position

Doravirine, in its various forms, has already gained a foothold in the HIV treatment market. The fixed-dose combination therapy, DELSTRIGO, is expected to see significant success due to its convenient dosing regimen. According to GlobalData, DELSTRIGO is forecasted to have peak annual sales of $369 million in the seven major markets (7MM) by 2023, while PIFELTRO, the single-agent form of doravirine, is expected to reach $144 million in 2025[2].

Market Projections

The global HIV market is anticipated to experience modest growth driven by the introduction of novel antiretroviral therapies, including integrase inhibitors and protease inhibitors. While doravirine-based therapies are not expected to reach blockbuster levels, they are projected to contribute substantially to this growth.

• Forecasted Sales: The combined sales of DELSTRIGO and PIFELTRO are expected to reach approximately $500 million across the 7MM by 2023. This indicates a strong market presence, though not at blockbuster levels[2].
• Competitive Landscape: The HIV market is highly competitive, with other major players like ViiV Healthcare, Gilead, and Janssen introducing new and innovative treatments. However, the convenience and efficacy of doravirine-based regimens position them well in this competitive landscape[5].

Regulatory Pathway

Merck plans to present detailed findings from the Phase 3 trials at a future scientific congress and will file the data with regulatory authorities. This step is crucial for potential approval of the DOR/ISL regimen, which could further expand the treatment options for people living with HIV[1][4].

Patient Impact

The development of a once-daily, oral, two-drug, single-tablet regimen like DOR/ISL is significant for patients. It offers a simpler and potentially more tolerable treatment option, which can improve adherence and quality of life.

"We are encouraged by the results from these Phase 3 trials evaluating a once-daily, oral, two-drug, single-tablet regimen of doravirine and islatravir," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. "We are committed to advancing our clinical programs for islatravir in combination with other antiretrovirals as potential options to help address the needs of people living with HIV."[1][4]

Future Directions

Merck is committed to advancing the clinical programs for islatravir in combination with other antiretrovirals. The ongoing ILLUMINATE clinical development program will continue to study this investigational treatment across diverse patient populations, further solidifying the potential of doravirine-based regimens in HIV treatment[3].

Key Takeaways

• Clinical Success: The DOR/ISL regimen has demonstrated non-inferiority to existing antiretroviral therapies in Phase 3 trials.
• Long-Term Efficacy: The combination of doravirine and islatravir has shown sustained viral suppression through 144 weeks.
• Market Potential: Doravirine-based therapies are expected to achieve significant sales, particularly with the fixed-dose combination DELSTRIGO.
• Regulatory Progress: Merck is moving forward with regulatory filings based on the positive Phase 3 trial results.
• Patient Benefits: The once-daily, two-drug regimen offers a simpler and potentially more tolerable treatment option for HIV patients.

FAQs

Q: What is the current status of the doravirine/islatravir regimen in clinical trials?

A: The doravirine/islatravir regimen has completed two pivotal Phase 3 trials, demonstrating non-inferiority to existing antiretroviral therapies and meeting primary safety objectives[1][4].

Q: How does the market forecast look for doravirine-based therapies?

A: According to GlobalData, the combined sales of DELSTRIGO and PIFELTRO are expected to reach approximately $500 million across the 7MM by 2023, with DELSTRIGO seeing the most success[2].

Q: What are the benefits of the doravirine/islatravir regimen for patients?

A: The regimen offers a once-daily, oral, two-drug, single-tablet option, which can improve adherence and quality of life for patients with HIV-1 infection[1][4].

Q: Are there any long-term efficacy data available for the doravirine/islatravir combination?

A: Yes, data from an ongoing Phase 2b clinical trial have shown that the combination maintains viral suppression through 144 weeks[3].

Q: What are Merck's plans for regulatory approval of the DOR/ISL regimen?

A: Merck plans to present detailed findings from the Phase 3 trials at a future scientific congress and will file the data with regulatory authorities[1][4].

Sources

1. Merck Announces Topline Results from Pivotal Phase 3 Trials Evaluating Investigational, Once-Daily, Oral, Two-Drug, Single-Tablet Regimen of Doravirine/Islatravir (DOR/ISL) for the Treatment of Adults with Virologically Suppressed HIV-1 Infection. Merck.
2. Merck should expect strong sales for two new HIV drugs, says GlobalData. Pharmaceutical Manufacturer.
3. Merck Presents New Data from Ongoing Phase 2b Clinical Trial Evaluating Efficacy and Safety of Investigational Islatravir in Combination with Doravirine through 144 Weeks for HIV-1 Treatment at EACS. Merck.
4. Merck announces results from Phase 3 trials evaluating investigational regimen of doravirine/islatravir. European AIDS Treatment Group.
5. Global Drug Forecast and Market Analysis to 2025. GlobalData.

Last updated: 2025-01-01