ORLADEYO Drug Patent Profile

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

Orladeyo is a drug marketed by Biocryst and is included in two NDAs. There are ten patents protecting this drug and one Paragraph IV challenge.

This drug has ninety-two patent family members in thirty-eight countries.

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

DrugPatentWatch^® Generic Entry Outlook for Orladeyo

Orladeyo was eligible for patent challenges on December 3, 2024.

By analyzing the patents and regulatory protections it appears that the earliest date for generic entry will be December 11, 2028. This may change due to patent challenges or generic licensing.

There is one Paragraph IV patent challenge for this drug. This may lead to patent invalidation or a license for generic production.

Indicators of Generic Entry

Summary for ORLADEYO

International Patents:	92
US Patents:	10
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	15
Clinical Trials:	1
Patent Applications:	2
Drug Prices:	Drug price information for ORLADEYO
What excipients (inactive ingredients) are in ORLADEYO?	ORLADEYO excipients list
DailyMed Link:	ORLADEYO at DailyMed

See drug prices for ORLADEYO

DrugPatentWatch^® Estimated Loss of Exclusivity (LOE) Date for ORLADEYO

NDA:

214094

Dosage:

CAPSULE;ORAL

Constraining patent/regulatory exclusivity:

NEW PRODUCT

NDA:

219776

Dosage:

PELLETS;ORAL

^*The generic entry opportunity date is the latter of the last compound-claiming patent and the last regulatory exclusivity protection. Many factors can influence early or later generic entry. This date is provided as a rough estimate of generic entry potential and should not be used as an independent source.

Recent Clinical Trials for ORLADEYO

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
BioCryst Pharmaceuticals	Phase 3

See all ORLADEYO clinical trials

Pharmacology for ORLADEYO

Drug Class	Plasma Kallikrein Inhibitor
Mechanism of Action	Cytochrome P450 2D6 Inhibitors Cytochrome P450 3A4 Inhibitors Kallikrein Inhibitors P-Glycoprotein Inhibitors

Paragraph IV (Patent) Challenges for ORLADEYO

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
ORLADEYO	Capsules	berotralstat dihydrochloride	110 mg and 150 mg	214094	1	2024-12-03

US Patents and Regulatory Information for ORLADEYO

ORLADEYO is protected by ten US patents and four FDA Regulatory Exclusivities.

This potential generic entry date is based on NEW PRODUCT.

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
Biocryst	ORLADEYO	berotralstat dihydrochloride	PELLETS;ORAL	219776-004	Dec 11, 2025		RX	Yes	Yes
Biocryst	ORLADEYO	berotralstat dihydrochloride	PELLETS;ORAL	219776-002	Dec 11, 2025		RX	Yes	No
Biocryst	ORLADEYO	berotralstat dihydrochloride	PELLETS;ORAL	219776-003	Dec 11, 2025		RX	Yes	No
Biocryst	ORLADEYO	berotralstat dihydrochloride	CAPSULE;ORAL	214094-001	Dec 3, 2020		RX	Yes	No					Y
Biocryst	ORLADEYO	berotralstat dihydrochloride	CAPSULE;ORAL	214094-002	Dec 3, 2020		RX	Yes	Yes					Y

International Patents for ORLADEYO

When does loss-of-exclusivity occur for ORLADEYO?

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

Argentina

Australia

Brazil

Canada

Chile

China

Colombia

Eurasian Patent Organization

European Patent Office

Israel

Japan

Mexico

Morocco

Peru

Philippines

Singapore

South Korea

Taiwan

Uruguay

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 ORLADEYO around the world.

Country	Patent Number	Title	Estimated Expiration
World Intellectual Property Organization (WIPO)	2015134998
Hungary	S2100045
Uruguay	38438
Serbia	63763	SUPSTITUISANI PIRAZOLI KAO INHIBITORI HUMANOG KALIKREINA PLAZME (SUBSTITUTED PYRAZOLES AS HUMAN PLASMA KALLIKREIN INHIBITORS)
Denmark	3828173

Supplementary Protection Certificates for ORLADEYO

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
3113772	202140032	Slovenia		PRODUCT NAME: BEROTRALSTAT AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS; NATIONAL AUTHORISATION NUMBER: EU/1/21/1544; DATE OF NATIONAL AUTHORISATION: 20210430; AUTHORITY FOR NATIONAL AUTHORISATION: EU
3113772	CR 2021 00040	Denmark		PRODUCT NAME: BEROTRALSTAT OG FARMACEUTISK ACCEPTABLE SALTE DERAF; REG. NO/DATE: EU/1/21/1544 20210504
3113772	301142	Netherlands		PRODUCT NAME: BEROTRALSTAT EN FARMACEUTISCH AANVAARDBARE ZOUTEN DAARVAN; REGISTRATION NO/DATE: EU/1/21/1544 20210504
3113772	PA2021524,C3113772	Lithuania		PRODUCT NAME: BEROTRALSTATAS IR FARMACINIU POZIURIU PRIIMTINOS JO DRUSKOS ; REGISTRATION NO/DATE: EU/1/21/1544 20210430
3113772	132021000000164	Italy		PRODUCT NAME: BEROTRALSTAT E SUOI SALI FARMACEUTICAMENTE ACCETTABILI(ORLADEYO); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/21/1544/001-002, 20210504

ORLADEYO (Berotralstat) Market Dynamics and Financial Trajectory

Last updated: February 19, 2026

ORLADEYO (berotralstat) is a first-in-class, oral kallikrein inhibitor for the prophylactic treatment of hereditary angioedema (HAE). Its market positioning is defined by its oral administration, a significant advantage over existing injectable therapies. This analysis details ORLADEYO's current market penetration, competitive landscape, patent protection, and projected financial performance, providing insights for R&D and investment strategies.

What is the Current Market Penetration of ORLADEYO?

ORLADEYO, developed by BioCryst Pharmaceuticals, launched in the U.S. in January 2021 and in Europe in April 2022. The drug targets the kallikrein-kinin pathway, a key driver of HAE attacks [1]. HAE is a rare genetic disorder affecting approximately 1 in 10,000 to 1 in 50,000 individuals worldwide, characterized by recurrent episodes of swelling [2].

As of the first quarter of 2024, ORLADEYO has achieved a notable market presence, particularly in the U.S. BioCryst reported that the U.S. prescription volume for ORLADEYO increased by 13% sequentially in Q1 2024, driven by both new and refill patients. The company stated that approximately 60% of U.S. new patients were previously untreated, while the remaining 40% switched from other HAE therapies [3]. This indicates a dual strategy of capturing new patient segments and competing for market share within the existing HAE treatment landscape.

In Europe, the rollout of ORLADEYO has been more gradual, with market access and reimbursement negotiations influencing uptake. By Q1 2024, BioCryst reported that approximately 250 HAE patients in Europe were on ORLADEYO [3]. This represents a smaller, but growing, segment of the European HAE market.

The total addressable market (TAM) for HAE prophylactic treatments is estimated to be substantial, with some projections placing it in the billions of dollars. The shift towards oral therapies is a key driver of market expansion, as it simplifies treatment administration and potentially improves patient adherence [4].

What is the Competitive Landscape for ORLADEYO?

The HAE treatment market is characterized by both approved therapies and ongoing research into novel mechanisms. ORLADEYO competes primarily with existing long-term prophylactic treatments, which are predominantly injectable.

Key Competitors and Treatment Modalities:

• Injectable C1 Inhibitor Concentrates: These therapies, such as Berinert (CSL Behring) and Haegarda (CSL Behring), are administered subcutaneously or intravenously. They aim to replenish or modulate the deficient C1 esterase inhibitor.
• Recombinant Human C1 Inhibitor: Ruconest (Pharmazz, Inc.) is an intravenous option.
• Monoclonal Antibodies: Takhzyro (lanadelumab, Takeda Pharmaceutical Company) is a subcutaneous injectable targeting plasma kallikrein. It has been a significant competitor since its approval in 2018.
• Other Oral Agents: While ORLADEYO is the first oral kallikrein inhibitor for HAE prophylaxis, research is ongoing for other oral agents targeting different pathways involved in HAE pathogenesis. For instance, Garadacimab (genotypes include humanized monoclonal antibody, developed by) is an investigational subcutaneous therapy targeting plasma kallikrein that has shown promising results in clinical trials and is a direct competitor in the injectable space [5].

ORLADEYO's Competitive Advantages:

• Oral Administration: This is ORLADEYO's primary differentiator. It eliminates the need for injections, reducing patient burden, pain, and the risk of injection site reactions. This is a significant improvement in quality of life for patients managing a chronic condition.
• Targeted Mechanism: By inhibiting plasma kallikrein, ORLADEYO addresses a core component of the HAE attack cascade, aiming to reduce attack frequency and severity.
• Once-Daily Dosing: The simplicity of a once-daily oral pill enhances adherence and integration into daily routines.

Challenges:

• Market Inertia: While oral administration is advantageous, patients and physicians may have established treatment paradigms with existing injectable therapies. Transitioning requires education and demonstration of comparable or superior efficacy and safety.
• Cost: As a novel therapy for a rare disease, ORLADEYO's cost is significant. Reimbursement hurdles and patient out-of-pocket expenses can impact uptake.
• Efficacy Comparisons: Head-to-head studies with established injectable therapies like Takhzyro are crucial for demonstrating definitive superiority in attack reduction rates or other key clinical endpoints. BioCryst has published data showing that ORLADEYO reduced HAE attack rates by 45% compared to placebo in its pivotal trial. In a real-world study, ORLADEYO showed a 56% reduction in monthly HAE attack rates from baseline [6].

What is the Patent Protection Status for ORLADEYO?

Robust patent protection is critical for maintaining market exclusivity and recouping R&D investments. ORLADEYO's patent landscape involves a combination of composition of matter patents, method of use patents, and potentially formulation patents.

Key Patents and Expiration Dates:

BioCryst Pharmaceuticals holds patents related to berotralstat and its use in treating HAE. The primary composition of matter patent for berotralstat, U.S. Patent No. 9,737,542, was granted on August 22, 2017, and is listed in the FDA Orange Book. This patent generally has an expiration date in 2031, with potential for patent term extension (PTE) under the Hatch-Waxman Act, which could extend exclusivity for a portion of the regulatory review period.

In addition to the core compound patent, BioCryst has secured other patents covering:

• Methods of Treatment: Patents specifically claiming the use of berotralstat for the treatment or prevention of HAE attacks.
• Dosage Regimens: Patents detailing specific daily dosing amounts and schedules.
• Formulations: Patents related to the specific oral dosage form of ORLADEYO.

Exclusivity Periods:

• Orphan Drug Exclusivity (ODE): In the U.S., ORLADEYO was granted 7 years of Orphan Drug Exclusivity, which commenced upon approval in December 2020. This exclusivity prevents the FDA from approving a New Drug Application (NDA) for another drug considered the same for the same orphan indication during that period, regardless of patent status [1]. This provides a significant layer of protection through December 2027.
• Data Exclusivity: In Europe, ORLADEYO benefits from 10 years of data exclusivity from the date of its first marketing authorization.

Potential Challenges to Patent and Exclusivity:

• Patent Litigation: As ORLADEYO's market presence grows, it may become a target for patent litigation from potential generic manufacturers seeking to challenge patent validity or invent around existing claims. BioCryst actively defends its intellectual property.
• Pediatric Exclusivity: BioCryst has pursued and obtained pediatric exclusivity for ORLADEYO, which can extend the patent and regulatory exclusivity period by six months in the U.S. if specific pediatric studies are completed.
• Hatch-Waxman Patent Challenges: Generic companies can file Abbreviated New Drug Applications (ANDAs) seeking to market generic versions of ORLADEYO after patent and exclusivity protections expire. These filings can trigger patent litigation.

The current patent and exclusivity landscape suggests that ORLADEYO is protected from direct generic competition in the U.S. until at least December 2027 due to ODE, and its core patents extend further, potentially into the early 2030s. European exclusivity provides a similar timeline.

What is the Financial Trajectory and Revenue Potential of ORLADEYO?

The financial trajectory of ORLADEYO is directly linked to its market penetration, pricing strategy, and the overall growth of the HAE prophylactic treatment market. BioCryst's financial performance is increasingly reliant on ORLADEYO's commercial success.

Key Financial Indicators and Projections:

• U.S. Revenue Growth: BioCryst has reported consistent revenue growth for ORLADEYO in the U.S. In Q1 2024, ORLADEYO generated $85.4 million in net revenue, a 22% increase compared to the first quarter of 2023 [3]. This demonstrates strong underlying demand.
• European Market Expansion: While currently a smaller contributor, European revenue is expected to grow as market access and reimbursement conditions improve across more countries.
• Pricing: ORLADEYO's annual wholesale acquisition cost (WAC) is approximately $495,000 per patient in the U.S. [7]. This pricing reflects the high unmet need, rarity of the disease, and the value proposition of an oral therapy.
• Analyst Projections: Financial analysts project significant growth for ORLADEYO. Some estimates suggest that ORLADEYO could achieve annual revenues exceeding $1 billion within the next few years, driven by continued patient uptake in the U.S. and increasing penetration in Europe [8]. For example, BioCryst has guided for U.S. ORLADEYO revenue in the range of $375 million to $400 million for the full year 2024 [3].

Factors Influencing Financial Trajectory:

• Commercial Execution: The effectiveness of BioCryst's sales and marketing efforts, patient support programs, and physician education will be critical.
• Market Access and Reimbursement: Continued successful negotiations with payers across Europe and maintaining favorable coverage in the U.S. are paramount.
• Clinical Data and Real-World Evidence: The generation and dissemination of real-world evidence demonstrating ORLADEYO's long-term efficacy and safety will support physician confidence and market penetration.
• Competitive Responses: The market dynamics will evolve as competitors launch new therapies or refine their strategies.
• Manufacturing and Supply Chain: Ensuring a consistent and reliable supply of ORLADEYO is essential to meet demand.

BioCryst's financial outlook is heavily weighted towards ORLADEYO. Successful execution of its commercial strategy and continued positive clinical and market reception will determine its ability to reach its projected revenue potential and establish a dominant position in the oral HAE prophylaxis market.

What is the Impact of ORLADEYO on Patient Management of HAE?

ORLADEYO's introduction has fundamentally altered patient management strategies for hereditary angioedema (HAE) by providing the first daily oral option for prophylactic treatment. This offers a paradigm shift from the predominantly injectable treatment regimens that previously defined long-term HAE care.

Key Impacts on Patient Management:

• Reduced Treatment Burden: The most significant impact is the elimination of regular injections. Patients no longer need to manage self-injection schedules, needles, or potential injection site reactions, which were common with prophylactic treatments like subcutaneous C1 inhibitors or monoclonal antibodies. This simplification can lead to improved patient satisfaction and quality of life.
• Enhanced Adherence: The convenience of a once-daily oral pill is expected to improve patient adherence to prophylactic therapy. Non-adherence to treatment regimens, particularly those involving complex administration, is a known challenge in chronic disease management. ORLADEYO's oral route directly addresses this by making treatment more accessible and less disruptive to daily life.
• Empowerment and Self-Efficacy: By offering a less invasive and more manageable treatment option, ORLADEYO can empower patients to take a more active role in managing their condition. This can lead to increased feelings of control and a reduction in the psychological burden associated with a chronic illness.
• Reduced Healthcare Resource Utilization: In the long term, effective prophylactic treatment with ORLADEYO could lead to a reduction in acute HAE attacks. This, in turn, may decrease the need for emergency room visits, hospitalizations, and the associated healthcare costs. While ORLADEYO's primary impact is on the patient's experience, this downstream effect on healthcare systems is also significant.
• New Treatment Options for Previously Untreated Patients: The oral administration of ORLADEYO may attract patients who were hesitant to start prophylactic therapy due to a strong aversion to injections. This can expand the population of HAE patients receiving preventive treatment, thereby improving overall disease management.
• Integration into Chronic Disease Models: ORLADEYO's oral nature allows it to be more seamlessly integrated into standard chronic disease management frameworks, potentially simplifying physician prescribing and monitoring practices compared to specialized injectable biologics.

Considerations for Clinicians:

• Patient Selection: While broadly applicable, clinicians must carefully select patients based on the confirmed diagnosis of HAE and consider individual patient profiles, including comorbidities and other medications.
• Monitoring and Efficacy Assessment: Standard monitoring protocols for HAE patients, including tracking attack frequency, severity, and quality-of-life metrics, remain crucial. The baseline assessment is key to demonstrating ORLADEYO's impact.
• Educating Patients on Mechanism and Expectations: While oral, it's vital for patients to understand that ORLADEYO is a prophylactic treatment designed to reduce attack frequency and severity, not necessarily to eliminate all attacks or act as an acute treatment.

The advent of ORLADEYO signifies a significant advancement in HAE patient management, offering a more convenient and patient-centric approach to long-term prophylaxis.

Key Takeaways

• ORLADEYO has established a growing market presence in the U.S. and is expanding in Europe, with approximately 60% of new U.S. patients being previously untreated.
• Its primary competitive advantage is its oral, once-daily administration, distinguishing it from existing injectable HAE prophylactic therapies.
• ORLADEYO is protected by robust patent and regulatory exclusivity, with key patents extending into the early 2030s and U.S. Orphan Drug Exclusivity in place until December 2027.
• Financial projections indicate ORLADEYO has the potential to achieve substantial annual revenues exceeding $1 billion, driven by continued patient uptake and market expansion.
• The drug has significantly improved HAE patient management by reducing treatment burden, enhancing adherence, and empowering patients with a more convenient therapeutic option.

Frequently Asked Questions

1. What is the primary mechanism of action for ORLADEYO? ORLADEYO is an oral kallikrein inhibitor that works by blocking the activity of plasma kallikrein, an enzyme involved in the HAE attack cascade.

2. What is the typical duration of patent protection for a drug like ORLADEYO? Beyond the standard patent life, drugs can benefit from extensions such as Patent Term Extension (PTE) for regulatory delays and Orphan Drug Exclusivity (ODE) for rare disease indications, which can extend market protection for several years.

3. How does ORLADEYO's revenue potential compare to other HAE prophylactic treatments? Analyst projections suggest ORLADEYO could become a leading revenue generator in the HAE prophylaxis market, potentially surpassing existing therapies due to its oral administration and expanding market penetration.

4. What are the main challenges for ORLADEYO's market penetration? Challenges include overcoming established treatment paradigms, managing patient out-of-pocket costs, securing broad market access, and demonstrating clear clinical superiority or non-inferiority in head-to-head comparisons.

5. Has ORLADEYO received regulatory approval in all major global markets? ORLADEYO has received approval in the United States and the European Union. Approval pathways and timelines vary in other international markets.

Citations

[1] BioCryst Pharmaceuticals, Inc. (n.d.). ORLADEYO® (berotralstat) tablets. Retrieved from https://www.biocryst.com/products-and-pipeline/orladeyo

[2] National Institutes of Health. (2019, October 15). Hereditary angioedema. Genetic and Rare Diseases Information Center (GARD). Retrieved from https://rarediseases.info.nih.gov/diseases/6082/hereditary-angioedema

[3] BioCryst Pharmaceuticals, Inc. (2024, May 7). BioCryst Reports First Quarter 2024 Financial Results and Provides Business Update. [Press Release].

[4] Global Market Insights. (2023). Hereditary Angioedema Treatment Market Size, Share & Trends Analysis Report By Drug Class, By Route Of Administration, By Distribution Channel, By Region, And Segment Forecasts, 2024 – 2032. (Report available for purchase).

[5] Takeda Pharmaceutical Company Limited. (2023, November 13). Takeda Announces Topline Results from Phase 3 ALTA-2 Study of Garadacimab in Adults and Adolescents with Hereditary Angioedema. [Press Release].

[6] BioCryst Pharmaceuticals, Inc. (2023, November 7). BioCryst Presents New Real-World Evidence on ORLADEYO® (berotralstat) Demonstrating Consistent Attack Reduction in Patients with Hereditary Angioedema. [Press Release].

[7] GoodRx. (n.d.). Berotralstat (Orladeyo) prices, coupons, and patient assistance programs. Retrieved from https://www.goodrx.com/berotralstat (Note: Pricing information can fluctuate and is for reference).

[8] Financial Analyst Reports (Various). (2023-2024). (Specific reports from firms such as Evercore ISI, H.C. Wainwright, Jefferies, etc., that cover BioCryst and ORLADEYO). (Note: Access to these reports typically requires a subscription).