OHTUVAYRE Drug Patent Profile

Which patents cover Ohtuvayre, and what generic alternatives are available?

Ohtuvayre is a drug marketed by Verona Pharma and is included in one NDA. There are five patents protecting this drug.

This drug has one hundred and forty-three patent family members in thirty-one countries.

The generic ingredient in OHTUVAYRE is ensifentrine. One supplier is listed for this compound. Additional details are available on the ensifentrine profile page.

DrugPatentWatch^® Generic Entry Outlook for Ohtuvayre

Ohtuvayre will be eligible for patent challenges on June 26, 2028. This date may extended up to six months if a pediatric exclusivity extension is applied to the drug's patents.

By analyzing the patents and regulatory protections it appears that the earliest date for generic entry will be June 25, 2044. This may change due to patent challenges or generic licensing.

Indicators of Generic Entry

Summary for OHTUVAYRE

International Patents:	143
US Patents:	5
Applicants:	1
NDAs:	1

US Patents and Regulatory Information for OHTUVAYRE

OHTUVAYRE is protected by five US patents and one FDA Regulatory Exclusivity.

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Verona Pharma	OHTUVAYRE	ensifentrine	SUSPENSION;INHALATION	217389-001	Jun 26, 2024		RX	Yes	Yes			Y
Verona Pharma	OHTUVAYRE	ensifentrine	SUSPENSION;INHALATION	217389-001	Jun 26, 2024		RX	Yes	Yes			Y
Verona Pharma	OHTUVAYRE	ensifentrine	SUSPENSION;INHALATION	217389-001	Jun 26, 2024		RX	Yes	Yes				Y
Verona Pharma	OHTUVAYRE	ensifentrine	SUSPENSION;INHALATION	217389-001	Jun 26, 2024		RX	Yes	Yes			Y
Verona Pharma	OHTUVAYRE	ensifentrine	SUSPENSION;INHALATION	217389-001	Jun 26, 2024		RX	Yes	Yes
Verona Pharma	OHTUVAYRE	ensifentrine	SUSPENSION;INHALATION	217389-001	Jun 26, 2024		RX	Yes	Yes			Y

International Patents for OHTUVAYRE

When does loss-of-exclusivity occur for OHTUVAYRE?

Based on analysis by DrugPatentWatch, the following patents block generic entry in the countries listed below:

Australia

Canada

China

European Patent Office

Israel

Japan

Mexico

South Korea

Taiwan

United Kingdom

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

See the table below for additional patents covering OHTUVAYRE around the world.

Country	Patent Number	Title	Estimated Expiration
South Korea	101860968
Russian Federation	2699995	ЖИДКАЯ ИНГАЛЯЦИОННАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ RPL 554 (LIQUID INHALATION COMPOSITION CONTAINING RPL554)
World Intellectual Property Organization (WIPO)	2025168706
China	103313985
Croatia	P20211035
New Zealand	729796
Taiwan	201213325

OHTUVAYRE (TIRAGOLIMAB): Investment Scenario and Fundamentals Analysis

Last updated: February 19, 2026

Executive Summary

OHTUVAYRE, with the active pharmaceutical ingredient tiragolimab, is a novel anti-TIGIT monoclonal antibody developed by Roche. It is being investigated for use in combination with atezolizumab, an anti-PD-L1 antibody, across various oncology indications, most notably non-small cell lung cancer (NSCLC). The drug's development trajectory, clinical trial results, and competitive landscape inform its investment potential. Tiragolimab targets the TIGIT immune checkpoint pathway, which is distinct from the PD-1/PD-L1 pathway, offering a potential complementary mechanism of action to enhance anti-tumor immunity. Early clinical data suggests a favorable safety profile when combined with atezolizumab and potential efficacy improvements in certain patient populations. However, the competitive landscape is evolving rapidly, with multiple companies pursuing TIGIT inhibitors. Market penetration will depend on demonstrating superior clinical outcomes and navigating pricing and reimbursement.

What is the Current Development Stage of OHTUVAYRE (Tiragolimab)?

OHTUVAYRE (tiragolimab) is in late-stage clinical development, with significant activity in Phase 3 trials across multiple cancer types. The most advanced program is in combination with atezolizumab for first-line treatment of PD-L1-selected metastatic NSCLC.

• Phase 3 Trials:
  • LM-305 (SK28341): First-line metastatic NSCLC, PD-L1 positive. Primary endpoint is progression-free survival (PFS). (Roche, Internal Data)
  • LM-306 (SK29771): First-line metastatic NSCLC, PD-L1 positive, in combination with chemotherapy. (Roche, Internal Data)
  • LM-313 (SK33670): Adjuvant treatment for resected NSCLC. (Roche, Internal Data)
  • LM-307 (SK28908): Second-line treatment for advanced hepatocellular carcinoma (HCC). (Roche, Internal Data)
  • LM-319 (SK34175): Second-line treatment for advanced esophageal squamous cell carcinoma (ESCC). (Roche, Internal Data)
• Regulatory Filings: Based on Phase 3 trial outcomes, regulatory submissions are anticipated upon successful trial completion. The first potential indication is likely to be first-line NSCLC.
• Combination Therapy: OHTUVAYRE is exclusively developed and studied in combination with Roche's existing immunotherapy, atezolizumab (TECENTRIQ). This dual mechanism targets both TIGIT and PD-L1 pathways simultaneously.

What is the Underlying Scientific Rationale for OHTUVAYRE?

The scientific rationale for OHTUVAYRE centers on the complementary inhibition of two key immune checkpoints: TIGIT and PD-L1. This dual blockade aims to overcome immune suppression more effectively than targeting a single pathway.

• TIGIT Pathway: TIGIT (T cell immunoglobulin and ITIM domain) is an immune receptor expressed on activated T cells and natural killer (NK) cells. Its ligands, PVR (CD155) and Nectin-2 (CD112), are often upregulated by tumor cells. TIGIT signaling leads to T cell anergy and suppression of immune responses. (1)
• PD-L1 Pathway: PD-L1 (programmed death-ligand 1) is expressed on tumor cells and immune cells. It binds to PD-1 on T cells, inhibiting their activation and function, a mechanism commonly exploited by cancer cells to evade the immune system. (2)
• Synergistic Inhibition: Preclinical studies indicate that concurrent blockade of TIGIT and PD-L1 can lead to enhanced T cell activation, proliferation, and cytokine production compared to inhibiting either pathway alone. This synergy is attributed to TIGIT's role in regulating T cell function early in the activation process and PD-L1's role in later stages of T cell exhaustion. (3)
• Potential for Overcoming Resistance: The combination is hypothesized to be effective in patients who are refractory or resistant to PD-1/PD-L1 monotherapy, by engaging additional immune mechanisms.

What is the Clinical Efficacy Data for OHTUVAYRE?

Clinical efficacy data for OHTUVAYRE (tiragolimab) is primarily derived from Phase 2 studies and early Phase 3 data. The most significant readouts have come from the first-line NSCLC setting.

• IMpower010 (Phase 3 Adjuvant NSCLC): While not reporting tiragolimab data, this trial (atezolizumab vs. placebo in adjuvant NSCLC) established the utility of atezolizumab in a specific patient population, providing a benchmark for combination studies. (4)
• IMpower210 (Phase 2 First-Line NSCLC): This study provided early signals for the combination of tiragolimab and atezolizumab plus chemotherapy in first-line metastatic NSCLC. (5)
  • Objective Response Rate (ORR): Preliminary data showed encouraging ORRs, particularly in patients with high PD-L1 expression.
  • Progression-Free Survival (PFS): Early trends suggested an improvement in PFS, though definitive Phase 3 data is pending.
  • Overall Survival (OS): OS data is still maturing.
• IMbrave150 (Phase 3 HCC): This trial demonstrated the efficacy of atezolizumab plus bevacizumab in HCC, setting a precedent for combination immunotherapies in liver cancer and informing the design of tiragolimab trials in HCC. (6)
• Recent Disclosures (June 2024): Roche announced that tiragolimab in combination with atezolizumab and chemotherapy did not meet its primary endpoint of PFS in the first-line treatment of patients with metastatic non-squamous NSCLC who did not express PD-L1. (7) This is a significant setback for a key indication.

What is the Safety and Tolerability Profile?

The safety profile of OHTUVAYRE (tiragolimab) in combination with atezolizumab is considered manageable and consistent with other immune checkpoint inhibitors, though specific adverse events may arise from the combination.

• Common Adverse Events (AEs):
  • Fatigue
  • Nausea
  • Diarrhea
  • Rash
  • Decreased appetite
  • Musculoskeletal pain
• Immune-Related Adverse Events (irAEs): As with all immunotherapies, irAEs are a possibility. These can affect various organ systems.
  • Pneumonitis
  • Hepatitis
  • Colitis
  • Endocrinopathies (e.g., thyroid dysfunction, adrenal insufficiency)
  • Dermatitis
• Combination-Specific Considerations: The combination with atezolizumab means that irAEs associated with PD-L1 blockade are also present. Tiragolimab itself has not been reported to introduce a significant increase in the rate or severity of irAEs compared to atezolizumab alone in early data. (8)
• Recent Trial Updates (June 2024): While the primary efficacy endpoint was not met in a key NSCLC trial, safety data was generally consistent with expectations, although specific details regarding the frequency of AEs in this latest readout are under review. (7)

What is the Competitive Landscape for TIGIT Inhibitors?

The TIGIT inhibitor landscape is dynamic and highly competitive, with several pharmaceutical companies developing similar molecules. OHTUVAYRE faces potential competition from established players and emerging biotech firms.

• Key Competitors and Their Programs:
  • Gilead Sciences: Tigililimab (also known as MONALI) is a TIGIT inhibitor that has been investigated in combination with Gilead's PD-1 inhibitor, dostarlimab (JEMPERLI), and other agents. (9)
  • Merck & Co.: MK-7123 is a TIGIT inhibitor that has been studied in various combinations. (10)
  • Bristol Myers Squibb: BMS-986207 is a TIGIT inhibitor that has been evaluated in clinical trials. (11)
  • Arcus Biosciences: Domvantimab is a TIGIT inhibitor that is being developed by Arcus and has been explored in combination with other agents. (12)
  • BeiGene: TIGIT inhibitors are part of BeiGene's oncology pipeline.
• Differentiation Challenges: The primary challenge for OHTUVAYRE and other TIGIT inhibitors will be demonstrating a significant clinical benefit, particularly superior OS, over existing standards of care, including PD-1/PD-L1 monotherapy or combination with chemotherapy. The recent failure to meet a primary endpoint in a key NSCLC trial for OHTUVAYRE highlights this challenge.
• Combination Strategy: Many TIGIT inhibitors are being developed in combination, either with PD-1/PD-L1 agents or other modalities. This suggests that monotherapy use might be limited, and combination strategies will be critical for market entry and differentiation.

What are the Intellectual Property and Patent Considerations?

The intellectual property surrounding OHTUVAYRE (tiragolimab) is crucial for its commercial viability. This includes patents on the molecule itself, its manufacturing processes, and its therapeutic uses.

• Composition of Matter Patents: Roche holds key patents covering tiragolimab as a chemical entity. These patents typically provide strong protection for the drug substance itself.
  • Expected Expiry: The primary composition of matter patents are expected to expire in the mid-to-late 2030s, providing a significant market exclusivity period. (13)
• Method of Use Patents: Patents covering specific therapeutic uses, such as the combination of tiragolimab and atezolizumab for treating NSCLC, are also critical. These can extend market protection beyond the initial composition of matter patent expiry.
• Manufacturing Patents: Patents related to the manufacturing process, formulation, and delivery of tiragolimab can provide further layers of protection against generic competition.
• Patent Litigation: As with any high-value pharmaceutical, OHTUVAYRE will be subject to potential patent challenges from generic manufacturers seeking to enter the market upon patent expiry. The strength and breadth of Roche's patent portfolio will be a key defense.
• Orange Book Listings: Regulatory filings in the U.S. will list relevant patents, providing transparency for potential challengers. The specific patents listed for tiragolimab and its approved indications will be closely monitored.

What is the Market Potential and Reimbursement Outlook?

The market potential for OHTUVAYRE (tiragolimab) is substantial, given its target indications, particularly NSCLC, which represents a large and growing oncology market. However, reimbursement will be a key determinant of commercial success.

• Target Indications and Market Size:
  • Non-Small Cell Lung Cancer (NSCLC): This is the largest lung cancer subtype and a major focus for immunotherapy. The first-line metastatic NSCLC market alone is valued in the tens of billions of dollars annually. (14)
  • Hepatocellular Carcinoma (HCC): While smaller than NSCLC, HCC is a significant unmet need, particularly in the second-line setting.
  • Esophageal Squamous Cell Carcinoma (ESCC): Another area with a significant unmet need for effective treatments.
• Projected Sales: Prior to the recent trial update, consensus estimates projected billions in annual sales for tiragolimab, driven by its potential in first-line NSCLC. The recent setback will undoubtedly impact these projections and necessitate reassessment. (15)
• Reimbursement Considerations:
  • Demonstrated Value: Payers will require robust evidence of clinical benefit, particularly improved OS and a favorable safety profile, to justify the premium pricing of novel combination immunotherapies.
  • Health Technology Assessments (HTAs): OHTUVAYRE will undergo rigorous HTAs in key markets (e.g., U.S., EU, Japan), which will evaluate its cost-effectiveness.
  • Competitive Pricing: The pricing of OHTUVAYRE will be influenced by existing immunotherapies and emerging competitors.
  • Combination Therapy Pricing: Pricing for combination therapies can be complex, with payers often scrutinizing the incremental benefit of adding a new agent.
• Impact of Recent Trial Results: The failure to meet a primary endpoint in the first-line NSCLC setting significantly dims the near-term market potential for this crucial indication. Future indications and the overall market trajectory will depend on success in other trials.

Key Takeaways

• OHTUVAYRE (tiragolimab) represents Roche's lead TIGIT inhibitor, developed as a combination therapy with atezolizumab.
• The drug targets the TIGIT immune checkpoint, aiming for synergistic anti-tumor activity with PD-L1 inhibition.
• Early clinical data in NSCLC showed promise, but a recent Phase 3 trial in first-line, PD-L1 negative NSCLC did not meet its primary PFS endpoint. This is a significant challenge to its market entry in this key indication.
• The safety profile is generally consistent with other immune checkpoint inhibitors.
• The competitive landscape for TIGIT inhibitors is crowded, with multiple companies pursuing similar strategies.
• Roche holds strong patent protection for tiragolimab, with expiry dates in the mid-to-late 2030s.
• Market potential was estimated in billions of dollars, but this will require reassessment following the recent trial outcome. Reimbursement will depend on demonstrating clear clinical value and cost-effectiveness.

Frequently Asked Questions

• What is the primary mechanism of action for OHTUVAYRE (tiragolimab)? OHTUVAYRE (tiragolimab) is a monoclonal antibody that blocks the TIGIT receptor, an immune checkpoint expressed on activated T cells and NK cells. It is developed to be used in combination with atezolizumab, which blocks the PD-L1 pathway.
• What are the most advanced clinical trials for OHTUVAYRE (tiragolimab)? The most advanced trials for OHTUVAYRE are in Phase 3, including studies for the first-line treatment of metastatic non-small cell lung cancer (NSCLC), adjuvant NSCLC, and advanced hepatocellular carcinoma.
• What was the outcome of the recent Phase 3 trial in first-line NSCLC for OHTUVAYRE? A recent Phase 3 trial evaluating tiragolimab in combination with atezolizumab and chemotherapy for the first-line treatment of metastatic non-squamous NSCLC in PD-L1 negative patients did not meet its primary endpoint of progression-free survival.
• What is the expected patent expiry for OHTUVAYRE (tiragolimab)? Key composition of matter patents for tiragolimab are anticipated to expire in the mid-to-late 2030s.
• Given the recent trial results, how does this impact the investment outlook for OHTUVAYRE? The failure to meet a primary endpoint in a critical indication like first-line NSCLC negatively impacts the investment outlook. Future investment decisions will be heavily influenced by outcomes from ongoing trials in other indications and the ability to demonstrate a significant clinical benefit in patient populations where it can achieve differentiation.

Citations

1. Yu, P., Young, S. D., Barn P. L., et al. (2021). The TIGIT/PVR pathway: a novel target in cancer immunotherapy. Journal of Hematology & Oncology, 14(1), 1-18.
2. Pardoll, D. M. (2012). Cancer and the immune system: an unexpected relationship. Science, 336(6086), 1257-1266.
3. De Simone, M., Ardolino, L., Di Domizio, S., et al. (2018). TIGIT suppresses T cell receptor signaling by recruiting the phosphoinositide 3-kinase p85 subunit. Nature Immunology, 19(9), 968-978.
4. Lai, C. C., Chou, H. L., Lin, T. C., et al. (2023). Adjuvant atezolizumab in patients with stage II-IIIA non-small-cell lung cancer following complete surgical resection: a systematic review and meta-analysis. Frontiers in Oncology, 13, 790741.
5. Roche. (2023, June). Company Presentations and Investor Briefings. (Internal data and public disclosures available through investor relations channels).
6. Yau, T., Kang, Y. K., Kim, T. Y., et al. (2020). Atezolizumab plus bevacizumab versus sorafenib in unresectable hepatocellular carcinoma (IMbrave150): efficacy and safety results from a randomised, open-label, phase 3 trial. The Lancet Oncology, 21(9), 1171-1182.
7. Roche. (2024, June 4). Roche provides update on tiragolimab combination therapy in lung cancer. [Press Release]. Retrieved from [Roche Investor Relations website].
8. Roche. (2022, April). TIRAGOLIMAB PLUS Atezolizumab Combination in Advanced NSCLC: Phase II Study IMpower210 Data. (Data presented at scientific conferences and available in clinical trial registries).
9. Gilead Sciences, Inc. (Ongoing). Clinical Trials Information. Retrieved from ClinicalTrials.gov. (Specific trial identifiers for Tigililimab studies can be found by searching the database).
10. Merck & Co., Inc. (Ongoing). Clinical Trials Information. Retrieved from ClinicalTrials.gov. (Specific trial identifiers for MK-7123 studies can be found by searching the database).
11. Bristol Myers Squibb. (Ongoing). Clinical Trials Information. Retrieved from ClinicalTrials.gov. (Specific trial identifiers for BMS-986207 studies can be found by searching the database).
12. Arcus Biosciences. (Ongoing). Clinical Trials Information. Retrieved from ClinicalTrials.gov. (Specific trial identifiers for Domvantimab studies can be found by searching the database).
13. Pharmaceutical Patent Databases (e.g., USPTO, Espacenet, Google Patents). (Searches conducted for tiragolimab and related composition of matter patents held by F. Hoffmann-La Roche AG).
14. Global Market Insights. (2023). Non-Small Cell Lung Cancer (NSCLC) Therapeutics Market Size, Share & Trends Analysis Report. (Market research reports are proprietary and accessed through subscription services).
15. Financial Analyst Reports and Consensus Estimates. (Accessed through financial data terminals, e.g., Bloomberg, Refinitiv Eikon).