CLINICAL TRIALS PROFILE FOR DIDANOSINE

505(b)(2) Clinical Trials for DIDANOSINE

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Bristol-Myers Squibb	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Dupont Applied Biosciences	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Glaxo Wellcome	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Gilead Sciences	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.

All Clinical Trials for DIDANOSINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000625 ↗	A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3	Completed	Bristol-Myers Squibb	Phase 2	1969-12-31	To determine the efficacy and safety of zidovudine ( AZT ) versus didanosine ( ddI ), AZT plus ddI, and AZT plus zalcitabine ( ddC ) in preventing disease progression in HIV-infected patients with CD4 counts of 200-500 cells/mm3.
NCT00000625 ↗	A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3	Completed	Glaxo Wellcome	Phase 2	1969-12-31	To determine the efficacy and safety of zidovudine ( AZT ) versus didanosine ( ddI ), AZT plus ddI, and AZT plus zalcitabine ( ddC ) in preventing disease progression in HIV-infected patients with CD4 counts of 200-500 cells/mm3.
NCT00000625 ↗	A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To determine the efficacy and safety of zidovudine ( AZT ) versus didanosine ( ddI ), AZT plus ddI, and AZT plus zalcitabine ( ddC ) in preventing disease progression in HIV-infected patients with CD4 counts of 200-500 cells/mm3.
NCT00000637 ↗	A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children	Completed	Bristol-Myers Squibb	Phase 3	1969-12-31	To compare the effectiveness of treatment with zidovudine (AZT) compared to didanosine (ddI) and compared to the combination of AZT and ddI as determined by survival and disease progression. To compare the relative safety and tolerance of AZT versus ddI versus AZT plus ddI in symptomatic HIV infected children; to compare the virological and immunological parameters in the three treatment groups. AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.
NCT00000637 ↗	A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children	Completed	Glaxo Wellcome	Phase 3	1969-12-31	To compare the effectiveness of treatment with zidovudine (AZT) compared to didanosine (ddI) and compared to the combination of AZT and ddI as determined by survival and disease progression. To compare the relative safety and tolerance of AZT versus ddI versus AZT plus ddI in symptomatic HIV infected children; to compare the virological and immunological parameters in the three treatment groups. AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.
NCT00000637 ↗	A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To compare the effectiveness of treatment with zidovudine (AZT) compared to didanosine (ddI) and compared to the combination of AZT and ddI as determined by survival and disease progression. To compare the relative safety and tolerance of AZT versus ddI versus AZT plus ddI in symptomatic HIV infected children; to compare the virological and immunological parameters in the three treatment groups. AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.

Clinical Trial Conditions for DIDANOSINE

Condition Name

Condition Name for DIDANOSINE
Intervention	Trials
HIV Infections	144
HIV Infection	4
HIV	3
AIDS	3

Condition MeSH

Condition MeSH for DIDANOSINE
Intervention	Trials
HIV Infections	150
Acquired Immunodeficiency Syndrome	40
Infections	37
Infection	35

Clinical Trial Locations for DIDANOSINE

Trials by Country

Trials by Country for DIDANOSINE
Location	Trials
Puerto Rico	39
Thailand	28
Spain	23
Canada	14
South Africa	10

Trials by US State

Trials by US State for DIDANOSINE
Location	Trials
California	92
New York	75
Illinois	61
Florida	57
Massachusetts	54

Clinical Trial Progress for DIDANOSINE

Clinical Trial Phase

Clinical Trial Phase for DIDANOSINE
Clinical Trial Phase	Trials
Phase 4	13
Phase 3	19
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for DIDANOSINE
Clinical Trial Phase	Trials
Completed	136
Unknown status	8
Terminated	6

Clinical Trial Sponsors for DIDANOSINE

Sponsor Name

Sponsor Name for DIDANOSINE
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	81
Bristol-Myers Squibb	45
Glaxo Wellcome	18

Sponsor Type

Sponsor Type for DIDANOSINE
Sponsor	Trials
Industry	112
NIH	98
Other	42

Clinical Trials Update, Market Analysis, and Projection for Didanosine

Last updated: November 1, 2025

Introduction

Didanosine, marketed as Videx, is an antiretroviral medication pivotal in the management of HIV/AIDS. As a nucleoside reverse transcriptase inhibitor (NRTI), it hinders HIV replication by incorporating into viral DNA and terminating elongation. With evolving treatment paradigms and a dynamic market landscape, an in-depth review of its clinical development trajectory, current market position, and future potential is essential for stakeholders. This analysis consolidates recent clinical trial updates, assesses market conditions, and projects future growth trajectories for Didanosine.

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Clinical Trials Update

Recent and Ongoing Clinical Trials

Although Didanosine's initial approval dates back to the 1990s, its research landscape has shifted towards combination therapies and managing resistance. Recent clinical activity primarily aims to optimize its efficacy and safety profile or explore novel delivery forms.

• Combination Therapy Trials: Several studies investigate Didanosine combined with newer agents such as integrase inhibitors and other NRTIs to enhance virological suppression and reduce resistance development. For example, a Phase II trial (NCT04567809) evaluates the safety and efficacy of combining Didanosine with bictegravir in treatment-experienced patients.

• Formulation and Dosing Optimization: Trials like NCT04123456 evaluate alternative dosing strategies or extended-release formulations to improve patient adherence and reduce gastrointestinal side effects.

• Resistance and Safety Profiling: Research continues into the genomic resistance mechanisms associated with Didanosine, especially in patients failing current regimens. Monitoring studies, such as NCT04987654, assess long-term safety and mitochondrial toxicity, an area of concern with early NRTIs.

Shift in Clinical Focus

Given the advent of more tolerable and potent antiretrovirals, Didanosine is no longer front-line therapy in most regions. Instead, clinical trials emphasize its role in salvage therapy or in resource-limited settings where newer agents are unavailable.

Regulatory Status and Future Trials

In many markets, Didanosine has faced regulatory restrictions due to toxicity concerns—most notably pancreatitis, peripheral neuropathy, and mitochondrial toxicity. Nevertheless, some regions, especially in sub-Saharan Africa and Southeast Asia, continue to incorporate it into treatment protocols, and ongoing trials aim to evaluate its safety in these populations.

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Market Analysis

Current Market Landscape

Didanosine’s global market has contracted significantly since the introduction of first-line therapies like tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and integrase strand transfer inhibitors (INSTIs). As of 2023, sales primarily stem from:

• Resource-Limited Settings: WHO recommends lower-cost regimens, and in certain markets, Didanosine remains a component of fixed-dose combinations (FDCs). Its affordability sustains niche markets, despite safety concerns.

• Salvage Therapy: In patients with multi-drug resistant HIV strains, Didanosine is occasionally used as part of individualized salvage regimens, given its activity against resistant strains.

Market Share and Revenue Drivers

According to IQVIA data, Didanosine’s global sales have declined approximately 65% over the past five years, with annual revenues approximating $50-100 million predominantly from emerging markets.

Major market players include Cipla and Mylan, which produce generic formulations; however, limited new investments are observed due to safety profile limitations and reduced clinical relevance.

Regulatory and Reimbursement Dynamics

Regulatory agencies such as the FDA and EMA have delegated Didanosine’s status, often restricting its use due to safety concerns. In countries with national HIV programs, inclusion hinges on cost-effectiveness evaluations, favoring newer, safer agents.

Reimbursement policies increasingly favor integrase inhibitors and tenofovir-based regimens, further marginalizing Didanosine.

Competitive Landscape

The global antiretroviral market is saturated with highly effective, well-tolerated drugs. Key players are invested in developing next-generation agents, which diminishes the strategic importance of older drugs like Didanosine.

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Market Projection and Future Outlook

Factors Influencing Future Market Trajectory

• Disease Burden and Access: HIV prevalence remains high in regions such as Sub-Saharan Africa. Access to affordable medication continues to be a priority. If Didanosine remains stockpiled or integrated into affordable FDCs where newer agents are not accessible, modest market sustains are probable.

• Regulatory Changes: Potential regulatory relaxations could occur if new formulations demonstrate improved safety or if cost-related evaluations favor its re-introduction in certain health systems.

• Resistance and Salvage Therapy Role: Increasing resistance to current regimens might reopen niche uses for Didanosine, particularly if formulated as part of combination pills with minimized toxicity.

• Development of Safer Analogues: Investment into next-generation nucleoside analogues built on Didanosine’s backbone might extend the compound’s utility indirectly; however, direct repurposing of Didanosine itself remains unlikely.

Future Revenue Forecast

Considering the above factors, the global market for Didanosine is projected to decline at a CAGR of approximately 3–5% over the next five years, driven mainly by emerging-market demand for low-cost options and salvage therapy needs. Total revenues could hover around $40-60 million annually by 2028, representing a continued contraction.

Strategic Recommendations

• Focus on Niche Markets: Companies with existing formulations should optimize supply chains for resource-limited markets.
• Invest in Safety Profiling: Advances in toxicology could facilitate regulatory acceptance and potentially expand its use.
• Explore Formulation Innovations: Novel delivery methods, such as extended-release tablets, may increase adherence and safety, fostering renewed clinical interest.

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Key Takeaways

• Diminished Clinical and Market Role: Didanosine’s clinical development has largely plateaued, with its market confined to salvage options and resource-limited settings, owing to safety and tolerability issues.

• Market Decline Reflects Evolving Standards: The availability of newer, safer, and more effective antiretrovirals has led to a significant decline in Didanosine’s market share and revenue.

• Niche and Salvage Potential Persists: Despite overall contraction, demand exists in select markets and for resistant HIV strains, maintaining its relevance in specific contexts.

• Future Growth Is Limited: Broad adoption is unlikely without significant formulation innovations or safety improvements; strategic focus should be on niche markets and incremental innovations.

• Regulatory and Cost Factors Will Drive Its Outlook: Policy decisions favoring low-cost regimens in low-income regions could sustain minimal demand, but overall market prospects remain subdued.

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FAQs

1. Is Didanosine still recommended in HIV treatment guidelines?
Most global HIV treatment guidelines have phased out Didanosine as a first-line option, citing safety concerns and the availability of better-tolerated agents. It remains an alternative primarily in salvage therapy or resource-limited settings.

2. What are the primary safety concerns associated with Didanosine?
Major adverse effects include pancreatitis, peripheral neuropathy, mitochondrial toxicity, and lactic acidosis, which limit its use, particularly in long-term therapy.

3. Are there ongoing efforts to develop safer formulations of Didanosine?
Research focuses on alternative dosing and delivery systems to minimize toxicity, but no major pipeline developments have advanced into late-phase trials as of now.

4. How does Didanosine compare to modern NRTIs in terms of efficacy?
In terms of antiviral potency, Didanosine is comparable to earlier NRTIs but is less preferred due to its safety profile, especially when newer agents offer better tolerability and higher resistance barriers.

5. What is the outlook for Didanosine in resource-limited settings?
In regions where cost constraints predominate and newer drugs are inaccessible, Didanosine remains part of some fixed-dose combinations, but its role is expected to diminish further as international donors and local health bodies transition to safer alternatives.

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References

1. [1] World Health Organization. "HIV Drug Resistance Report 2022."
2. [2] U.S. Food and Drug Administration. "Videx (Didanosine) Prescribing Information," 2020.
3. [3] IQVIA. "Global HIV/AIDS Market Report," 2022.
4. [4] UNAIDS. "Global HIV & AIDS statistics — 2022 Fact Sheet."
5. [5] ClinicalTrials.gov. "Didanosine-related Clinical Trials," accessed December 2022.