CLINICAL TRIALS PROFILE FOR ISENTRESS

All Clinical Trials for Isentress

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00485264 ↗	Safety and Pharmacokinetics (PK) of Raltegravir in HIV (Human Immunodeficiency Virus)-Infected Children and Adolescents	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 1/Phase 2	2007-09-17	Integrase is 1 of 3 HIV (Human Immunodeficiency Virus)-1 enzymes required for viral replication. Raltegravir is a drug that prevents integrase from working properly. This drug has been tested for safety and efficacy in adults, but this is the first study to examine raltegravir in children and adolescents. The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks to 18 years of age, by acquiring short and long term safety data, intensive and population pharmacokinetic (PK) data, and efficacy experience with raltegravir in HIV-infected children and adolescents.
NCT00485264 ↗	Safety and Pharmacokinetics (PK) of Raltegravir in HIV (Human Immunodeficiency Virus)-Infected Children and Adolescents	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1/Phase 2	2007-09-17	Integrase is 1 of 3 HIV (Human Immunodeficiency Virus)-1 enzymes required for viral replication. Raltegravir is a drug that prevents integrase from working properly. This drug has been tested for safety and efficacy in adults, but this is the first study to examine raltegravir in children and adolescents. The purpose of this study was to determine the appropriate dose for raltegravir across the pediatric age range from 4 weeks to 18 years of age, by acquiring short and long term safety data, intensive and population pharmacokinetic (PK) data, and efficacy experience with raltegravir in HIV-infected children and adolescents.
NCT00525733 ↗	Standard Antiretroviral v. Multi-class Therapy in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects (ADARC 2007-01)	Completed	Aaron Diamond AIDS Research Center	N/A	2007-10-01	The researchers are involved in a phase II, randomized, two-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced darunavir with Truvada to a 5-drug multi-class regimen including truvada, darunavir/ritonavir/maraviroc/and raltegravir on acutely HIV-1-infected, antiretroviral (ARV) drug-naïve men and women. Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest. Hypotheses: - Multi-class antiretroviral therapy (ART) is superior to RTV-enhanced ATV in combination with Emtricitabine/Tenofovir DF (FTC/TDF) with respect to suppression of viral replication. - Multi-class ART is superior to RTV-enhanced ATV in combination with FTC/TDF with respect to immune reconstitution in peripheral blood and in the gastrointestinal mucosa. - Multi-class ART is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to tolerability.
NCT00525733 ↗	Standard Antiretroviral v. Multi-class Therapy in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects (ADARC 2007-01)	Completed	Merck Sharp & Dohme Corp.	N/A	2007-10-01	The researchers are involved in a phase II, randomized, two-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced darunavir with Truvada to a 5-drug multi-class regimen including truvada, darunavir/ritonavir/maraviroc/and raltegravir on acutely HIV-1-infected, antiretroviral (ARV) drug-naïve men and women. Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest. Hypotheses: - Multi-class antiretroviral therapy (ART) is superior to RTV-enhanced ATV in combination with Emtricitabine/Tenofovir DF (FTC/TDF) with respect to suppression of viral replication. - Multi-class ART is superior to RTV-enhanced ATV in combination with FTC/TDF with respect to immune reconstitution in peripheral blood and in the gastrointestinal mucosa. - Multi-class ART is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to tolerability.
NCT00525733 ↗	Standard Antiretroviral v. Multi-class Therapy in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects (ADARC 2007-01)	Completed	Pfizer	N/A	2007-10-01	The researchers are involved in a phase II, randomized, two-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced darunavir with Truvada to a 5-drug multi-class regimen including truvada, darunavir/ritonavir/maraviroc/and raltegravir on acutely HIV-1-infected, antiretroviral (ARV) drug-naïve men and women. Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest. Hypotheses: - Multi-class antiretroviral therapy (ART) is superior to RTV-enhanced ATV in combination with Emtricitabine/Tenofovir DF (FTC/TDF) with respect to suppression of viral replication. - Multi-class ART is superior to RTV-enhanced ATV in combination with FTC/TDF with respect to immune reconstitution in peripheral blood and in the gastrointestinal mucosa. - Multi-class ART is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to tolerability.

Clinical Trial Conditions for Isentress

Condition Name

Condition Name for Isentress
Intervention	Trials
HIV Infections	33
HIV	17
HIV Infection	12
HIV-1 Infection	6

Condition MeSH

Condition MeSH for Isentress
Intervention	Trials
HIV Infections	56
Acquired Immunodeficiency Syndrome	15
Infections	14
Infection	11

Clinical Trial Locations for Isentress

Trials by Country

Trials by Country for Isentress
Location	Trials
United States	96
Brazil	15
Canada	15
South Africa	14
France	10

Trials by US State

Trials by US State for Isentress
Location	Trials
California	12
Florida	7
North Carolina	7
New York	7
Massachusetts	7

Clinical Trial Progress for Isentress

Clinical Trial Phase

Clinical Trial Phase for Isentress
Clinical Trial Phase	Trials
Phase 4	30
Phase 3	12
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for Isentress
Clinical Trial Phase	Trials
Completed	67
Unknown status	9
Terminated	5

Clinical Trial Sponsors for Isentress

Sponsor Name

Sponsor Name for Isentress
Sponsor	Trials
Merck Sharp & Dohme Corp.	47
National Institute of Allergy and Infectious Diseases (NIAID)	7
Radboud University	5

Sponsor Type

Sponsor Type for Isentress
Sponsor	Trials
Other	117
Industry	69
NIH	13

Isentress: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Introduction to Isentress

Isentress, known generically as raltegravir, is a groundbreaking antiretroviral medication developed by Merck. It is the first in a new class of antiretrovirals that inhibits integrase, an enzyme crucial for the HIV replication process. Approved by the FDA on October 12, 2007, Isentress has been a significant addition to the treatment arsenal for HIV-1 infection[2].

Clinical Trials Overview

Early Clinical Trials: BENCHMARK-1 and BENCHMARK-2

The FDA approval of Isentress was based on the results of two pivotal clinical trials, BENCHMARK-1 and BENCHMARK-2. These trials involved treatment-experienced HIV-infected subjects who had failed antiretroviral therapies and had HIV virus resistant to at least one drug in each of the three available classes of oral antiretrovirals. The trials demonstrated that Isentress, when combined with optimized background therapy (OBT), significantly reduced HIV viral loads and increased CD4 cell counts compared to placebo plus OBT[4].

Recent Clinical Trials: Isentress HD

More recent clinical trials have focused on a new formulation of raltegravir, known as Isentress HD. In the Oncemrk trial, researchers compared the efficacy and safety of Isentress HD (1,200 mg once daily) plus Truvada to the older formulation of Isentress (400 mg twice daily) plus Truvada. The study found that both regimens were highly effective, with rapid reductions in viral loads and similar increases in CD4+ cell counts. By the 48th week, 89% of participants on the Isentress HD regimen and 88% on the older formulation had viral loads below 40 copies/mL[1].

Market Analysis

Market Position and Adoption

Isentress has been well-received by physicians and HIV experts due to its novel mechanism of action, high efficacy in treatment-experienced patients, favorable tolerability profile, and lack of need for ritonavir-boosting. Despite initial concerns about its twice-daily dosing, Merck’s strong commercial organization and commitment to the HIV market have facilitated its rapid uptake and widespread usage[2].

Market Projections

When Isentress was first approved, sales projections were optimistic, with estimates suggesting $20 million in 2007 and $1.1 billion by 2012. These projections were based on the drug's potential to treat a significant number of HIV patients, particularly those who had failed other therapies. The introduction of Isentress HD, with its once-daily dosing, is expected to further enhance its market position and appeal, especially in the treatment-naive population[2].

Safety and Efficacy

Safety Profile

Clinical trials have consistently shown that Isentress is well-tolerated. The BENCHMARK-1 and BENCHMARK-2 trials demonstrated that treatment with Isentress plus OBT was generally well-tolerated, with significant improvements in viral load reduction and CD4 cell counts compared to placebo. The Oncemrk trial also found that Isentress HD had a safety profile comparable to the older formulation[1][4].

Efficacy in Different Patient Groups

Isentress has shown high efficacy across various patient groups. In treatment-experienced patients, it has been effective in reducing viral loads and increasing CD4 cell counts. For patients with high baseline viral loads, the Oncemrk trial showed that Isentress HD was as effective as the older formulation in achieving viral suppression[1].

Future Developments and Competitors

Isentress HD and Once-Daily Regimens

The development of Isentress HD marks a significant advancement in HIV treatment, offering a once-daily regimen that can improve patient compliance. This formulation is expected to compete favorably with other once-daily antiretroviral regimens, enhancing Merck’s position in the HIV market[1].

Emerging Therapies

Merck is also advancing other clinical programs, such as the combination of doravirine and islatravir, which has shown promising results in Phase 3 trials. These new therapies aim to provide additional treatment options for people living with HIV, further solidifying Merck’s commitment to the HIV market[3].

Patent and Generic Entry

Current Patent Status

Isentress is protected by several patents, with the earliest date for generic entry projected to be September 11, 2029. This timeline may be subject to change due to patent challenges or generic licensing agreements[5].

Key Takeaways

• Clinical Efficacy: Isentress and its new formulation, Isentress HD, have demonstrated high efficacy in reducing viral loads and increasing CD4 cell counts in both treatment-experienced and treatment-naive patients.
• Market Position: Isentress has been well-received due to its novel mechanism of action and favorable safety profile, with strong market projections.
• Safety Profile: Clinical trials have shown that Isentress is well-tolerated, with a safety profile comparable to other antiretrovirals.
• Future Developments: The introduction of Isentress HD and other emerging therapies from Merck is expected to enhance treatment options for HIV patients.
• Patent Status: Isentress is protected by patents until at least 2029, ensuring its market exclusivity for several years.

FAQs

What is the mechanism of action of Isentress?

Isentress works by inhibiting the integrase enzyme, which is essential for the HIV replication process. This prevents the virus from integrating its genetic material into the host cell's DNA[2].

What are the key differences between Isentress and Isentress HD?

Isentress HD is a new formulation of raltegravir that allows for once-daily dosing, compared to the twice-daily dosing of the older formulation. Both formulations have shown similar efficacy and safety profiles[1].

How effective is Isentress in treatment-experienced patients?

Clinical trials, such as BENCHMARK-1 and BENCHMARK-2, have shown that Isentress is highly effective in reducing viral loads and increasing CD4 cell counts in treatment-experienced patients who have failed other antiretroviral therapies[4].

What are the potential competitors to Isentress in the HIV market?

Emerging therapies, including combinations like doravirine and islatravir, are being developed to provide additional treatment options for HIV patients. However, Isentress remains a strong contender due to its established efficacy and safety profile[3].

When can generic versions of Isentress be expected?

Generic versions of Isentress are projected to enter the market no earlier than September 11, 2029, based on current patent protections[5].

Sources

1. CATIE.ca: Isentress HD in clinical trials.
2. MM+M: Isentress.
3. Merck: 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.
4. CenterWatch: Isentress (raltegravir).
5. DrugPatentWatch: When will the patents on ISENTRESS expire, and when will generic entry occur?

Last updated: 2025-01-07