The Three Safest API Bets for 2026 Generic Drug Entry

Seventeen high-revenue small-molecule drugs were examined beyond simple patent expiry timelines. The review incorporated regulatory protections, competitor filings, and supply arrangements, factors that often surface late in the planning cycle and materially alter launch feasibility.

Timing proved decisive. Several of them that appeared viable at first narrowed quickly when secondary protections persisted, or competitive activity intensified. In some cases, the launch window compressed; in others, the investment case no longer held.

When these constraints were considered together, the field reduced sharply.

Only three Active Pharmaceutical Ingredients (APIs) continued to justify commitment heading into 2026.

This article presents those findings. It does not outline a general selection method; it identifies the APIs that remain defensible once practical barriers are fully accounted for.

The analysis was conducted using the Elixir platform, which continuously tracks drug patents and regulatory events that directly impact the timing of generic drug launches across various jurisdictions. Elixir gathers different signals, such as patent grants and abandonments, oppositions, pediatric exclusivities, new-entity exclusivities, ANDA activity, and Paragraph IV litigation. These signals are obtained from organizations like the USPTO, the EPO, and the Orange Book, and are integrated into a unified decision-making framework.

This method enables the assessment to identify when risks emerge, not just whether they are present. Consequently, active pharmaceutical ingredients (APIs) are evaluated at key points where portfolio decisions are most susceptible to delays, escalations, or loss of flexibility.

Commercial Relevance Filter: APIs That Retained Economic Gravity

Only APIs with steady and meaningful market demand were taken forward. Instead of focusing on short-term sales spikes, the review examined whether products continued to perform over several years of pricing pressure, new treatments, and competitive entry.

APIs showing clear signs of long-term decline were removed early. For these products, declining demand would make it difficult to recoup development costs, regardless of progress in other areas. The remaining APIs continue to attract consistent use and generate sufficient revenue to support realistic, generic timelines through 2026 and beyond.

APIs That Remained Relevant Despite Changing Sales Trends

From the initial set of APIs, a smaller subset remained after sales direction and overall market size were considered. Growth alone was not treated as a requirement. Some products continued to expand, while others experienced declining sales but retained strong positions due to established use, large patient populations, or slower generic uptake.

APIs were removed only when declining sales clearly pointed to shrinking long-term relevance. Where demand was expected to remain meaningful through the development window, those products were retained for further evaluation. This step ensured that the shortlist reflected commercial relevance over time rather than short-term movement and avoided excluding APIs that remain strategically important despite near-term pressure.

The asterisk (*) marks the drugs with the strongest future growth forecasts, with certain high performers, like Tirzepatide, which generated $25.25 billion in the first three quarters of 2025, clearly standing out as key players.

APIs That Withstood Patent Constraints and Those That Did Not

Patent timing alone did not determine whether an API remained viable. While some core patents are approaching expiry, many products remain protected by additional patents that cover formulations, dosing schedules, combinations, and other variations that govern how the drug is marketed.

Each shortlisted API was reviewed to understand how these remaining patents affect real entry, not just theoretical access. In several cases, layered protections significantly narrowed or delayed viable launch options, even when the primary-molecule patent was no longer a barrier.

See the full patent portfolio and exclusivity dates on Elixir

Regulatory Exclusivity and Timing Constraints

Regulatory exclusivity, as checked via Elixir, further altered timing assumptions for several APIs.

Extensions related to new patient populations, pediatric studies, orphan status, or new product forms shifted launch windows beyond initial expectations for several APIs. These exclusivities were reviewed alongside development timelines to assess whether early investment would yield progress or result in prolonged delays. APIs were deprioritized when exclusivity periods extended market access too far into the future, creating a mismatch between effort and return.

This step ensured that shortlisted APIs aligned not only with patent access but also with realistic regulatory timelines, thereby allowing development to proceed without avoidable delays or idle capital.

Competitive Activity and Entry Pressure

For several APIs, competitive conditions have begun to form well ahead of visible patent or exclusivity milestones. APIs with advanced ANDA activity were therefore assessed not only for openness but also for whether sufficient commercial and operational space remains within emerging market structures.

This criterion helped distinguish APIs in which ANDA activity remains limited and strategic positioning remains possible from those in which entry conditions are already largely defined.

See the full Branded & Generic Competitors list on Elixir

Clinical trials of shortlisted drugs:

Across several shortlisted products, ongoing Phase III and IV trials by originators indicate continued lifecycle investment. These programs often precede new filings that reshape formulation, dosing, or use conditions.

In parallel, investigator-led trials conducted by academic institutions and hospitals point to potential downstream claims and new use cases that may not yet be visible in patent or regulatory datasets. While not all trials result in additional protections, sustained clinical activity increases the likelihood of late-emerging constraints.

APIs with extensive ongoing clinical programs were evaluated with caution, recognizing that apparent stability today may not hold through the execution window.

Rank	Brand Names	INNs	NCT numbers	Company/sponsor/collaborator	Phase	Indications	Start Date	Complete Date
1	Xarelto	Rivaroxaban	–	–	–	–	–	–
1	Revlimid	Lenalidomide	–	–	–	–	–	–
1	Eliquis	Apixaban	–	–	–	–	–	–
1	Farxiga/Forxiga	Dapagliflozin	–	–	–	–	–	–
1	Entresto	Sacubitril, Valsartan	–	–	–	–	–	–
2	Biktarvy	Bictegravir, Emtricitabine, Tenofovir alafenamide	NCT04944654	Chelsea and Westminster NHS Foundation TrustCollaborators Gilead SciencesImperial College London	4	HIV	Jan 2023	May 2023
			NCT06104306	Gilead Sciences	4	HIV	Dec 2023	Apr 2025
3	Tagrisso	Osimertinib	NCT05629234	AstraZeneca	3	Continuation of treatment on previous study (ROSY-T)	May 2023	Feb 2027
			NCT05120349	AstraZeneca	3	Non-Small Cell Lung Cancer (NSCLC)	Feb 2022	Aug 2027
			NCT06350097	AstraZeneca	3	Non-Small Cell Lung Cancer (NSCLC)	Apr 2024	May 2032
4	Trikafta	Elexacaftor, Tezacaftor, Ivacaftor	NCT05111145	Vertex Pharmaceuticals	3	Cystic Fibrosis	Jan 2022	Dec 2022
			NCT06460506	Vertex Pharmaceuticals	3	Cystic Fibrosis	Nov 2024	Sep 2027
			NCT04969224	Vertex Pharmaceuticals	3	Cough and physical activity in cystic fibrosis	Oct 2021	Jul 2022
			NCT05331183	Vertex Pharmaceuticals	3	Cystic Fibrosis	Nov 2022	Apr 2027
			NCT04545515	Vertex Pharmaceuticals	3	Cystic Fibrosis	Jan 2021	Mar 2023
			NCT05153317	Vertex Pharmaceuticals	3	Cystic Fibrosis	Jan 2021	Apr 2026
			NCT05033080	Vertex Pharmaceuticals	3	Cystic Fibrosis	Sep 2021	Nov 2023
			NCT05444257	Vertex Pharmaceuticals	3	Cystic Fibrosis	Nov 2022	Oct 2026
			NCT05882357	Vertex Pharmaceuticals	3	Cystic Fibrosis	Jun 2023	Sep 2025
			NCT04599465	Vertex Pharmaceuticals	3	Cystic Fibrosis	Jan 2021	Jul 2022
			NCT05274269	Vertex Pharmaceuticals	3	Cystic Fibrosis without an F508del Mutation	May 2022	Jul 2023
			NCT05076149	Vertex Pharmaceuticals	3	Cystic Fibrosis	Oct 2021	Nov 2023
5	Mounjaro/Zepbound	Tirzepatide	NCT05706506	Eli Lilly	4	Type 2 diabetes	Mar 2023	Oct 2023
			NCT04657003	Eli Lilly	3	Obesity	Mar 2021	Apr 2023
			NCT06914895	Eli Lilly	3	Type 1 diabetesObesity	Apr 2025	May 2027
			NCT06662383	Eli Lilly	3	Obesity	Nov 2011	Dec 2026
			NCT05822830	Eli Lilly	3	Obesity	Apr 2023	Nov 2024
			NCT06075667	Eli Lilly	3	Obesity	Oct 2023	Jul 2029
			NCT05556512	Eli Lilly	3	Obesity	Oct 2022	Oct 2027
			NCT04660643	Eli Lilly	3	Obesity	Mar 2021	May 2023
			NCT06439277	Eli Lilly	3	Obesity	Jun 2024	Dec 2030
			NCT06047548	Eli Lilly	3	Obesity	Sep 2023	MAy 2026
			NCT06962280	Eli Lilly	3	ObesityType 1 diabetes	May 2025	Dec 2027
			NCT05412004	Eli Lilly	3	ObesityObstructive sleep apnea	Jun 2022	Mar 2023
			NCT05564039	Eli Lilly	4	Type 2 diabetes	Nov 2022	Aug 2024
			NCT04657016	Eli Lilly	3	Obesity	Mar 2021	May 2023
			NCT04847557	Eli Lilly	3	ObesityHeart Failure With Preserved Ejection Fraction (HFpEF)	Apr 2021	Jul 2024
			NCT05260021	Eli Lilly	3	Type 2 diabetes	Apr 2022	Jan 2025
			NCT05433584	Eli Lilly	4	Type 2 diabetes	Aug 2022	Nov 2027
6	Ozempic	Semaglutide	NCT04873050	Novo Nordisk	4	Pre diabetes Postpartum disorder	Jan 2022	Mar 2026
			NCT05646706	Novo Nordisk	3	Obesity	Jan 2023	Nov 2024
			NCT05649137	Novo Nordisk	3	Obesity Type 2 diabetes	Jan 2023	Dec 2024
			NCT05564117	Novo Nordisk	3	Obesity	Oct 2022	May 2024
			NCT05478252	Novo Nordisk	3	Type 2 diabetes	Aug 2022	Sep 2023
			NCT04865770	Novo Nordisk	3	Chronic kidney disease in type 2 diabetes patients	Apr 2021	Nov 2024
			NCT04788511	Novo Nordisk	3	Heart failure Obesity	Mar 2021	Apr 2023
			NCT04777409	Novo Nordisk	3	Alzheimer’s Disease	May 2021	Oct 2026
			NCT04916470	Novo Nordisk	3	Heart failure ObesityType 2 diabetes	Jun 2021	Oct 2023
			NCT06571383	Novo Nordisk	4	Obesity	Sep 2024	Nov 2031
			NCT05035095	Novo Nordisk	3	Obesity	Sep 2021	May 2023
			NCT05891496	Novo Nordisk	3	Alzheimer’s Disease	Jun 2023	Sep 2025
			NCT04822181	Novo Nordisk	3	Non-alcoholic Steatohepatitis (NASH)	Apr 2024	Apr 2029
			NCT04707469	Novo Nordisk	3	Type 2 diabetes	Jan 2021	Mar 2023
			NCT05726227	Novo Nordisk	3	Obesity	Jul 2023	Dec 2026
			NCT05064735	Novo Nordisk	3	ObesityKnee osteoarthritis	Oct 2021	Sep 2023
			NCT04777396	Novo Nordisk	3	Alzheimer’s Disease	May 2021	Oct 2926
			NCT05579249	Novo Nordisk	4	Obesity	Jan 2023	Nov 2024
			NCT05035082	Novo Nordisk	4	Type 2 diabetes	Sep 2021	Jun 2025

Rank	Brand Names	INNs	NCT numbers	Company/sponsor/collaborator	Phase	Indications	Start Date	Complete Date
1	Revlimid	Lenalidomide	–	–	–	–	–	–
2	Trikafta	Elexacaftor, Tezacaftor, Ivacaftor	NCT04840862	University of Southern California	4	Checking kinetic parameter	May 2022	May 2024
			NCT05743946	Emory University	4	Non-cystic Fibrosis Bronchiectasis (NCFBE)	Apr 2023	Jan 2026
3	Tagrisso	Osimertinib	NCT05785208	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	4	Non-Small Cell Lung Cancer (NSCLC)	Jun 2022	Oct 2025
			NCT05748093	Maastricht University Medical Center	4	Non-Small Cell Lung Cancer (NSCLC)	Apr 2024	Sep 2026
			NCT04695925	Li ZhangCancer Hospital of Guangxi Medical UniversityFirst People’s Hospital of FoshanHenan Cancer Hospital	3	Non-Small Cell Lung Cancer (NSCLC)	Mar 2021	Dec 2027
4	Entresto	Sacubitril, Valsartan	NCT04971720	University of Alabama at Birmingham	3	ObesityCardiovascular DiseasesHypertension	Feb 2022	Jan 2027
			NCT06693674	Mayo Clinic	3	Congenital heart disease	Feb 2025	Dec 2026
			NCT04649229	Yale University	4	Heart Failure	May 2021	Oct 2025
5	Eliquis	Apixaban	NCT07189897	State University of New York – Upstate Medical University	4	Prevent blood clots after head and neck cancer surgery	Oct 2025	Dec 2027
			NCT06953726	VA Office of Research and Development	4	Atrial fibrillation	Jun 2025	Oct 2033
			NCT07005024	University of Vermont	3	Reduce the risk of blood clots and death in cancer patients	Aug 2025	Aug 2035
			NCT04168203	Brigham and Women’s Hospital	4	Deep Vein ThrombosisPulmonary EmbolismVenous Thromboembolism	Mar 2021	Apr 2025
			NCT04650087	Duke University	3	COVID-19	Feb 2021	Sep 2022
6	Biktarvy	Bictegravir, Emtricitabine, Tenofovir alafenamide	NCT05602506	Fundacion Clinic per a la Recerca Biomédica	4	HIV	Nov 2022	Jun 2024
			NCT05979311	ViiV Healthcare	3	HIV	Feb 2024	Feb 2027
			NCT05122754	Shanghai Public Health Clinical Center	4	HIV	Dec 2021	Apr 2024
			NCT05147740	Tulika Singh	4	HIV	Jul 2021	Dec 2022
			NCT07138144	José Antonio Mata Marín	4	HIV	Jul 2025	Jul 2026
			NCT06830668	National Center for AIDS/STD Control and Prevention, China CDC	4	HIV	Feb 2025	Dec 2026
			NCT04296695	Peking Union Medical College Hospital	4	HIV	Jul 2021	Dec 2023
7	Mounjaro/Zepbound	Tirzepatide	NCT06901245	Seattle Children’s Hospital	4	Obesity in patient with Prader-Willi Syndrome	May 2025	Dec 2026
			NCT07191873	Duke University	4	Idiopathic Intracranial Hypertension	Sep 2025	Sep 2027
			NCT06861439	Wake Forest University Health Sciences	4	Behavioral treatment	Jul 2025	Dec 2026
			NCT07218445	Mayo Clinic	4	Menopausal Vasomotor Symptoms and Biological Aging in Post-menopausal Women With Obesity	Sep 2025	Sep 2027
			NCT05708859	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	4	Coronary Atherosclerosis in type 2 diabetes patients	Jan 2024	May 2026
			NCT06657209	Stanford University	4	Fat distribution	Dec 2024	Dec 2027
			NCT06774079	University of Miami	4	Inflammatory Bowel Disease (IBD)	Mar 2025	MAr 2026
			NCT07057310	Mayo Clinic	4	Obesity in postmenopausal women	May 2025	Mar 2027
8	Farxiga/Forxiga	Dapagliflozin	NCT05174052	University of Oklahoma	3	Atrial fibrillation	Jun 2022	Apr 2025
			NCT04620590	Emerald Clinical Inc.	4	Type 2 diabetes patients with impaired renal function	Apr 2021	Nov 2023
			NCT05741658	Johns Hopkins University	4	Heart failure	Nov 2023	Dec 2025
			NCT05139914	Boston University	4	Type 2 Diabetes Endothelial Dysfunction	May 2022	Dec 2025
			NCT04792190	University of Rochester	4	Atrial fibrillation	Jul 2021	Jun 2023
			NCT05541484	Washington University School of Medicine	4	Type 1 diabetes	Oct 2022	Dec 2023
			NCT06785116	University of Michigan	4	Cardiovascular risk reduction	Mar 2025	Aug 2028
			NCT06140537	University of Colorado	4	Promoting kidney function and cardiovascular health in kidney transplant patient	Feb 2024	Dec 2028
			NCT07056699	The University of Texas Health Science Center at San Antonio	3	Type 1 diabetes	Oct 2025	Jun 2027
			NCT06263673	Mayo Clinic	4	Parkinson’s diseaseLewy body dementia	May 2024	Dec 2025
			NCT05390892	Brigham and Women’s Hospital	4	Cardiovascular and diabetic kidney disease in Type 2 Diabetes	Sep 2022	Mar 2029
			NCT05278962	University of Chicago	4	Heart failure (HF) patients with left ventricular assist devices (LVAD)	Sep 2022	Aug 2025
9	Ozempic	Semaglutide	NCT05788965	University of Minnesota	3	Cystic fibrosis related diabetes (CFRD).	Apr 2023	Dec 2024
			NCT05819853	University of Colorado	3	Polycystic ovary syndrome	Nov 2023	Jun 2028
			NCT05819138	University of Colorado	3	Type 1 diabetes	Jun 2023	Dec 2027
			NCT04979130	University of Colorado	4	Type 2 diabetes	Jan 2022	Oct 2024
			NCT05786521	The University of Texas Health Science Center at San Antonio	4	Lifestyle counseling	Apr 2023	May 2024
			NCT07218354	VA Office of Research and Development	3	Moderate to severe alcohol use disorder	Jan 2026	Jan 2029
			NCT06499857	University of Chicago	3	Atrial fibrillation	Apr 2025	Jun 2028
			NCT05780905	University of Washington	4	Type 2 diabetes	Jan 2024	Dec 2026
			NCT06814938	Mayo Clinic	4	Obesity	Feb 2025	Nov 2028
			NCT05548647	University of Pennsylvania	4	Behavioral Treatment	Jul 2022	May 2025
			NCT06042153	University of Texas Southwestern Medical Center	4	Type 2 diabetes with chronic dialysis patients	Dec 2023	Sep 2028
			NCT06706284	The University of Texas Health Science Center at San Antonio	4	Type 2 diabetes with spinal cord injury	Apr 2025	Jan 2029
			NCT07021937	University of Colorado	3	Obesity	May 2026	Apr 2031
			NCT07057310	Mayo Clinic	4	Obesity in postmenopausal women	May 2025	Mar 2027
10	Xarelto	Rivaroxaban	NCT06187311	Korea University Anam Hospital	4	non-valvular atrial fibrillation	Jan 2023	Jun 2027
			NCT04838808	University of Alberta	3	Type 2 Myocardial Infarctions	Apr 2021	Jan 2023
			NCT06978439	Children’s Hospital of Fudan University	4	Giant Coronary Artery Aneurysm After Kawasaki Disease	Jan 2024	Dec 2025
			NCT06103266	J.P.S Henriques	4	atrial fibrillation	Jan 2024	Dec 2025
			NCT05410275	University Hospital, Tours	3	Renal Disease	Dec 2022	Jan 2024
			NCT06812455	AHEPA University Hospital	4	radial artery occlusion (RAO)	Mar 2025	Mar 2029
			NCT06476301	RenJi Hospital	4	Early Postoperative Period for Patients With Bioprosthetic Valves	Aug 2024	Dec 2026
			NCT04967573	Shanghai Zhongshan Hospital	3	Distal Deep Vein Thrombosis	Aug 2021	Dec 2023
			NCT06108414	China National Center for Cardiovascular Diseases	4	atrial fibrillation	Sep 2024	Dec 2027
			NCT06986369	The University of Hong Kong	4	Atherosclerotic Vascular Diseases	May 2021	Mar 2024
			NCT05487950	Assistance Publique – Hôpitaux de Paris	4	Excessive Atrial Ectopy or Short Atrial Runs and High Embolism Risk (SHORT RUN AF)	Apr 2023	Apr 2027
			NCT05303818	Hospital do Servidor Público Estadual	4	Lower Limb Deep Vein Thrombosis in Colorectal Cancer	Jun 2022	Jun 2024
			NCT06901466	Chinese Academy of Medical Sciences, Fuwai Hospital	4	Antithrombotic Treatment Following Transcatheter Edge-to-Edge Repair	May 2025	Oct 2028
			NCT05029063	Ottawa Hospital Research Institute	3	Primary Thromboprophylaxis in Patients With Malignancy and Central Venous Catheters	Oct 2022	Dec 2027
			NCT05033314	University Health Network, Toronto	3	THromboprophylaxis In Sickle Cell Disease With Central Venous Catheters	Jun 2022	Oct 2024
			NCT07202897	Rennes University Hospital	3	Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain	Oct 2025	Oct 2030
			NCT04700826	University of Birmingham	4	Stroke, Premature Death and Cognitive Decline in Patients With Atrial Fibrillation	Jun 2021	Jan 2031
			NCT04229758	University of Texas at Austin	3	Intracranial Hemorrhage	Oct 2021	Feb 2027

APIs Where Supplier Access Still Supports Execution

Beyond patent and regulatory considerations, the ability to secure a reliable supply of APIs that align with development timelines and filing strategies varied significantly among products. For some APIs, control over key synthetic processes, limited Drug Master File (DMF) availability, or early capacity commitments to select partners have already restricted sourcing options. 

In these cases, supplier constraints emerged well before patent expiry or Abbreviated New Drug Application (ANDA) milestones, reducing flexibility for late-stage market entry. APIs that are still in contention are those for which supplier engagement is feasible, DMF access remains available, and manufacturing capacity can realistically support development and launch plans. 

This ensured that the shortlisted opportunities are not only legally and commercially viable but also executable from a supply perspective.

See the full list of API Suppliers & Manufacturers along with their contact list on Elixir

Partnerships Have Already Shaped Market Access

For several shortlisted APIs, access conditions have already been shaped through existing partnerships.

Collaborations formed to expand geographic reach, authorize generics, or co-promote products indicate that market entry is no longer open-ended. In these cases, distribution, pricing, and capacity are being actively managed through selected channels rather than left open to independent entry.

Examples across the shortlist show this pattern clearly. Partnerships around Xarelto, Ozempic, Tirzepatide, and Entresto indicate that access has been negotiated in advance, thereby limiting independent participation despite apparent openness regarding patent or exclusivity timelines.

At this stage, collaboration visibility functions as an exclusion filter. It removes APIs that would otherwise receive effort toward opportunities that are no longer structurally available.

Selected APIs:

A small set of APIs continued to remain viable once these factors were applied together.

• Lenalidomide retains relevance despite declining sales, as residual access pathways, supplier availability, and market structure continue to support controlled generic participation.
• Semaglutide remains viable not because access is straightforward, but because the scale of demand justifies navigating a tightly managed and competitive environment where timing and alignment are critical.
• Rivaroxaban occupies a position where ANDA activity is advanced, yet sufficient structural room remains under defined assumptions for disciplined entry.

Together, these outcomes reinforce a central conclusion: API viability is determined by how constraints converge over time, not by any single parameter in isolation.

What’s Next for your Generic Market Entry?

With the shortlist narrowed, the focus shifts from identifying opportunities to managing what remains changeable. The APIs that remain viable today will continue to evolve as patent, regulatory, and competitive events unfold unevenly over time. 

For example, Semaglutide, one of the shortlisted APIs, is still in the early stages of its lifecycle. However, its journey through the regulatory and patent landscape will not be straightforward. New indications, exclusivity periods, and clinical trial results could significantly impact its viability. 

Elixir helps you track key patent and regulatory events, such as new patent grants, ANDA filings, and exclusive rights that influence the timing of generic market entry. With Elixir’s real-time notifications, you can identify potential issues, like pediatric extensions or new regulatory exclusivities, before they become obstacles. 

Fill the form today to schedule a demo of Elixir.

Explore how it can help you proactively manage these risks, ensuring your API selection remains on track and allowing you to respond to changes before they disrupt your generic entry timeline.