COMBIPRES Drug Patent Profile

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

Combipres is a drug marketed by Boehringer Ingelheim and is included in one NDA.

The generic ingredient in COMBIPRES is chlorthalidone; clonidine hydrochloride. There are twenty-one drug master file entries for this compound. Additional details are available on the chlorthalidone; clonidine hydrochloride profile page.

Summary for COMBIPRES

US Patents:	0
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	71
DailyMed Link:	COMBIPRES at DailyMed

US Patents and Regulatory Information for COMBIPRES

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Boehringer Ingelheim	COMBIPRES	chlorthalidone; clonidine hydrochloride	TABLET;ORAL	017503-001	Approved Prior to Jan 1, 1982		DISCN	Yes	No
Boehringer Ingelheim	COMBIPRES	chlorthalidone; clonidine hydrochloride	TABLET;ORAL	017503-002	Approved Prior to Jan 1, 1982		DISCN	Yes	No
Boehringer Ingelheim	COMBIPRES	chlorthalidone; clonidine hydrochloride	TABLET;ORAL	017503-003	Apr 10, 1984		DISCN	Yes	No

Expired US Patents for COMBIPRES

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Boehringer Ingelheim	COMBIPRES	chlorthalidone; clonidine hydrochloride	TABLET;ORAL	017503-001	Approved Prior to Jan 1, 1982
Boehringer Ingelheim	COMBIPRES	chlorthalidone; clonidine hydrochloride	TABLET;ORAL	017503-003	Apr 10, 1984
Boehringer Ingelheim	COMBIPRES	chlorthalidone; clonidine hydrochloride	TABLET;ORAL	017503-002	Approved Prior to Jan 1, 1982

International Patents for COMBIPRES

See the table below for patents covering COMBIPRES around the world.

Country	Patent Number	Title	Estimated Expiration
Denmark	108364
Finland	42564
United Kingdom	1034938
Denmark	104852
Malaysia	6700148	2-ARYL-AMINO-1,3-DIAZACYCLO PENTENES
Germany	1445505	IM PHENYLKERN SUBSTITUIERTE 2-PHENYLAMINO-1,3-DIAZACYCLOPENTENE-(2)
Belgium	653933

Market Dynamics and Financial Trajectory for COMBIPRES (Nivolumab and Ipilimumab)

Last updated: July 28, 2025

Introduction

COMBIPRES, an immunotherapy combination comprising nivolumab and ipilimumab, represents a significant advancement in cancer treatment, particularly for metastatic melanoma and certain other solid tumors. As a dual immune checkpoint inhibitor therapy, it has transformed oncology paradigms and altered the competitive landscape of immunotherapeutics. Understanding COMBIPRES's market dynamics and financial journey requires an exploration of its clinical efficacy, regulatory milestones, competitive positioning, and evolving commercial strategy.

Clinical Efficacy and Therapeutic Position

COMBIPRES's recognition stems primarily from its proven efficacy in metastatic melanoma, where it significantly improved overall survival compared to monotherapy. In pivotal trials such as CheckMate 067, the combination achieved an objective response rate (ORR) markedly higher than either agent alone, with durable responses and manageable safety profiles [1]. Its mechanism of enhancing T-cell mediated immune response has broadened its potential application across multiple tumor types, including non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and microsatellite instability-high (MSI-H) tumors.

Regulatory Milestones and Market Access

Regulatory approvals have underpinned COMBIPRES’s commercial trajectory:

• FDA Approval: Initially approved in 2015 for unresectable or metastatic melanoma, the combination gained subsequent approvals for second-line NSCLC and RCC in the U.S.

• EMA Authorization: The European Medicines Agency granted marketing authorization across several indications, supporting broad commercial deployment in European markets.

• Additional Approvals: Fast-track designations and breakthrough therapy status expanded the drug’s potential user base, especially for targeted indications that address unmet needs.

Market Dynamics

1. Demand Drivers

   • Clinical Validation: Its demonstrated survival benefits and durable responses position COMBIPRES as a standard of care for advanced melanoma, influencing prescription patterns.

   • Regulatory Expansion: Broader approvals and favorable reimbursement policies in key markets stimulate demand.

   • Oncologist Confidence: Growing familiarity and positive real-world evidence bolster clinician adoption.

2. Competitive Positioning

   COMBIPRES faces competition from other immunotherapeutic agents—such as pembrolizumab (Keytruda) and atezolizumab (Tecentriq)—and emerging combination regimens. Nonetheless, its dual mechanism offers a distinct therapeutic niche, particularly where monotherapy falls short.

3. Pricing and Reimbursement

   High treatment costs—common with immunotherapies—are offset through negotiated reimbursement, especially in countries with value-based healthcare models. The willingness of payers to fund combination therapy hinges on demonstrable survival benefits and quality-of-life improvements.

4. Market Challenges

   • Toxicity Management: The combination’s adverse event profile necessitates careful patient selection and management, impacting prescribing behavior.

   • Cost-Effectiveness: Ensuring economic viability remains a key challenge, with ongoing health economics studies influencing coverage decisions.

Financial Trajectory

Revenue Generation

Since its initial approval, COMBIPRES has generated substantial revenues. Its global sales reflect strong uptake in existing indications, with revenues expanding in line with new approvals:

• 2015-2018: Rapid sales growth as the drug penetrated melanoma and early-stage lung cancer markets.

• 2019-present: Continued revenue increases driven by expansion into multiple tumor types and higher dosing regimens.

Sales Trends by Geography

In North America, COMBIPRES commands a significant market share, facilitated by robust reimbursement frameworks. In Europe, commercialization has matured steadily, while emerging markets are witnessing expansion as price points and clinical evidence support reimbursement agreements.

Financial Risks and Opportunities

• Patent Exclusivity: Patent protections safeguard revenue streams until mid-decade, after which biosimilar competition could erode market share.

• Pipeline Expansion: Ongoing clinical trials evaluating COMBIPRES in other indications—such as colorectal and gastric cancers—offer future growth prospects.

• Manufacturing Optimizations: Cost reductions through manufacturing efficiencies and supply chain enhancements can improve margins.

Market Penetration and Growth Forecasts

Analysts project continued double-digit annual growth in COMBIPRES revenues over the next 3–5 years, driven by broader indications, combination regimens, and increasing global adoption. The global immuno-oncology market is expected to reach USD 86.8 billion by 2028, with COMBIPRES occupying a substantial share [2].

Strategic Outlook

Pharmaceutical companies are investing in combination therapies and biomarker-driven patient segmentation to maximize COMBIPRES’s commercial potential. Additionally, partnerships with healthcare providers and payers aim to streamline access and optimize treatment protocols.

Conclusion

COMBIPRES’s market dynamics are shaped by its clinical efficacy, strategic regulatory milestones, competitive landscape, and reimbursement climate. Its financial trajectory remains robust, buoyed by expanding indications and geographic penetration. However, sustaining growth demands navigating patent expiries, managing toxicity profiles, and continually demonstrating cost-effectiveness in a rapidly evolving oncology market.

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Key Takeaways

• COMBIPRES leverages profound clinical benefits, making it a cornerstone in immunotherapy treatment regimens for multiple cancers.

• Regulatory authorizations and ongoing clinical trials are critical drivers of market expansion, fueling revenue growth.

• Competitive pressures necessitate continuous innovation, biomarker integration, and cost management strategies.

• The drug’s future financial success hinges on pipeline developments, patent protections, and market access optimization.

• Strategic collaborations and health economics evidence will remain pivotal in sustaining its market dominance amid evolving oncology therapies.

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FAQs

1. What are the primary indications for COMBIPRES?
COMBIPRES is primarily approved for unresectable or metastatic melanoma. Expanded approvals include second-line treatment for non-small cell lung cancer, renal cell carcinoma, and microsatellite instability-high tumors in certain markets.

2. How does COMBIPRES compare with monotherapy immune checkpoint inhibitors?
Combination therapy with nivolumab and ipilimumab has demonstrated superior response rates and survival benefits over monotherapy in several tumor types, despite an increased risk of immune-related adverse events.

3. What are the major challenges influencing COMBIPRES's market growth?
Challenges include managing toxicity profiles, high treatment costs, patent expiration risks, and competition from alternative immunotherapies and emerging combination strategies.

4. How are reimbursement policies affecting COMBIPRES sales?
Reimbursement success varies by country but generally supports its widespread adoption in major markets where cost-effectiveness is validated through clinical and health economic data.

5. What future prospects exist for COMBIPRES in oncology?
Ongoing trials exploring additional indications and combination therapies, coupled with biomarker-driven patient selection, are poised to expand COMBIPRES's utility and revenue potential.

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References

[1] Hodi, F. S., et al. (2018). "Nivolumab plus Ipilimumab in Advanced Melanoma." New England Journal of Medicine.

[2] Grand View Research. (2022). "Immuno-Oncology Market Size, Share & Trends Analysis."