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 sixteen patents protecting this drug and one Paragraph IV challenge.

This drug has ninety-four patent family members in thirty-nine 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 September 9, 2035. This may change due to patent challenges or generic licensing.

There has been one patent litigation case involving the patents protecting this drug, indicating strong interest in generic launch. Recent data indicate that 63% of patent challenges are decided in favor of the generic patent challenger and that 54% of successful patent challengers promptly launch generic drugs.

Indicators of Generic Entry

Summary for ORLADEYO

International Patents:	94
US Patents:	16
Applicants:	1
NDAs:	2
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	15
Clinical Trials:	1
Drug Prices:	Drug price information for ORLADEYO
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases 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

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 sixteen US patents and four FDA Regulatory Exclusivities.

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

Australia

Brazil

Canada

China

Croatia

Cyprus

Denmark

Eurasian Patent Organization

European Patent Office

France

Hungary

Israel

Japan

Lithuania

Luxembourg

Malaysia

Mexico

Morocco

Netherlands

New Zealand

Norway

Philippines

Poland

Portugal

San Marino

Serbia

Singapore

Slovenia

South Africa

South Korea

Spain

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
Australia	2015226855
Australia	2020260400
Australia	2022259742
Brazil	112016020199
Canada	2941380
Canada	3164693

Supplementary Protection Certificates for ORLADEYO

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
3113772	301142	Netherlands		PRODUCT NAME: BEROTRALSTAT EN FARMACEUTISCH AANVAARDBARE ZOUTEN DAARVAN; REGISTRATION NO/DATE: EU/1/21/1544 20210504
3113772	CA 2021 00040	Denmark		PRODUCT NAME: BEROTRALSTAT OG FARMACEUTISK ACCEPTABLE SALTE DERAF; REG. NO/DATE: EU/1/21/1544 20210504
3113772	PA2021524	Lithuania		PRODUCT NAME: BEROTRALSTATAS IR JO FARMACINIU POZIURIU PRIIMTINOS DRUSKOS ; REGISTRATION NO/DATE: EU/1/21/1544 20210430
3113772	LUC00233	Luxembourg		PRODUCT NAME: BEROTRALSTAT ET LES SELS PHARMACEUTIQUEMENT ACCEPTABLES QUI EN DERIVENT; AUTHORISATION NUMBER AND DATE: EU/1/21/1544 20210504
3113772	2021C/544	Belgium		PRODUCT NAME: BEROTRALSTAT ET SES SELS PHARMACEUTIQUEMENT ACCEPTABLES; AUTHORISATION NUMBER AND DATE: EU/1/21/1544/001 ET 002 20210504
3113772	122021000062	Germany		PRODUCT NAME: BEROTRALSTAT ODER EIN PHARMAZEUTISCH VERTRAEGLICHES SALZ DAVON; REGISTRATION NO/DATE: EU/1/21/1544 20210430

ORLADEYO market dynamics and financial trajectory: growth drivers, pricing pressure, payer risk, and exclusivity-to-competition timeline

Last updated: July 24, 2026

Executive summary

• ORLADEYO (berotralstat) is a plasma kallikrein inhibitor positioned for hereditary angioedema (HAE) prophylaxis. Commercial trajectory is driven by U.S. payer access, HAE patient migration from on-demand and other prophylaxis, and ongoing prescriber conversion in a niche specialty market.
• Near-term revenue risk is concentrated in formulary tightening, rebate intensity, and competitor penetration, with additional pressure from future generic/biosimilar-style entry risk not currently applicable to berotralstat (small-molecule; generic path tied to patent expiration and Paragraph IV outcomes).
• Key valuation implications depend on U.S. exclusivity and patent expiration timing and whether litigation settles or produces enforceable “entry-blocking” outcomes. These determine the effective revenue cap for ORLADEYO and the speed of any competition that would compress net pricing.

What is ORLADEYO (berotralstat) and what drives its market dynamics?

ORLADEYO (berotralstat) is an oral prophylactic for hereditary angioedema (HAE). The market is structured around specialty pharmacy distribution, prior authorization (PA), and patient-level sequencing across:

• On-demand therapies (acute attacks)
• Intravenous/subcutaneous prophylaxis
• Oral prophylaxis (class consolidation and switching)

How does the HAE prophylaxis market behave commercially?

• Low patient counts create high sensitivity to payer controls and specialty pharmacy throughput.
• Uptake is driven by total-cost framing (reducing attacks and rescue use), patient adherence (oral once-daily advantage vs injection burden), and payer coverage policies.
• Net revenue is disproportionately impacted by rebate structure and contracting because the category is competitive and prescriber behavior is payer-influenced.

What are the highest-leverage commercial drivers for berotralstat?

• Formulary placement and PA criteria in major commercial plans and PBMs.
• Conversion from injection-based prophylaxis where adherence and quality-of-life improvements support switching.
• Coverage for patient subgroups that fail or discontinue other prophylaxis due to tolerability, convenience, or inadequate control.

Where do market frictions typically show up?

• Step therapy, especially requiring trial/failure of injectables or on-demand management.
• Dose- and duration-based utilization review.
• Restrictive brand-only coverage where competitors secure preferred formulary tiers.

How many patents protect ORLADEYO and how does the patent estate shape the financial trajectory?

For a small molecule like berotralstat, the effective revenue curve is set by patent expiry and any ANDA/Paragraph IV challenges. The financial trajectory depends on:

• The “last day of exclusivity” across relevant patent families
• Settlement terms that can delay entry
• Enforcement strength and likelihood of maintaining injunctions

Patent estate mapping is required for an investment-grade revenue shelf-life forecast. Without the Orange Book listing and specific patent numbers tied to ORLADEYO, no complete expiration schedule or entry-risk map can be produced.

When does ORLADEYO lose exclusivity in the US, and what is the competition entry scenario?

A credible exclusivity-to-competition model requires:

• Drug-specific FDA exclusivity identifiers (including listed patents and their expiration)
• Any data exclusivity attached to the NDA
• Litigation history that establishes whether exclusivity is effectively extended via settlements

A complete, accurate exclusivity timeline cannot be stated here without ORLADEYO’s FDA Orange Book listing, patent numbers, and expiration dates.

What is the Orange Book status of ORLADEYO?

Orange Book status determines:

• Which patents are listed for the NDA
• Their expiration dates
• Whether patents are method-of-use vs formulation vs composition of matter
• Whether there are multiple expiration milestones that structure market segmentation

Orange Book status cannot be provided accurately here without the specific ORLADEYO Orange Book record.

What patent litigation affects ORLADEYO and how does it change revenue risk?

Paragraph IV challenges and related district court filings can reshape revenue risk by:

• Creating “entry-blocking” settlements that preserve branded pricing longer than pure patent expiry
• Forcing redesign around noninfringement theories
• Leading to earlier or later launch depending on injunction posture

Litigation risk cannot be quantified without the ORLADEYO suit/settlement docket data (case numbers, ANDA/applicant, asserted patents, and settlement dates).

How strong is the patent estate for berotralstat compared with key HAE prophylaxis competitors?

Commercial compression risk depends on competitor breadth:

• Extent of oral prophylaxis competition
• Strength of competitor patent estates
• Likelihood of rapid follow-on launches that pressure net pricing even before ORLADEYO exclusivity ends

No defensible head-to-head patent-strength ranking can be produced without competitor estates and ORLADEYO’s specific listed patents and expiration data.

Which companies are challenging ORLADEYO with generics, and what is the Paragraph IV timeline?

A Paragraph IV timeline needs:

• ANDA filer identities
• Listed patents challenged
• Notice dates and litigation filing dates
• Settlement or court outcomes

No accurate “who/when” can be stated without the ORLADEYO ANDA Paragraph IV record.

What is ORLADEYO’s FDA regulatory status and how does it impact adoption?

FDA status shapes commercial velocity through:

• Indication breadth (including HAEs subsets)
• Label constraints that affect prescribing
• Postmarketing safety requirements that may shape PA criteria

Regulatory milestones cannot be detailed here without the specific FDA review/label data points for ORLADEYO.

What formulations are protected by ORLADEYO patents and what manufacturing/IP barriers exist for generics?

For small molecules, generic entry barriers typically come from:

• Composition of matter coverage for berotralstat
• Salt form, polymorph, and solid-state form claims if applicable
• Manufacturing process patents (less common but potentially relevant)
• Method-of-use coverage (route/dose regimen claims)

Formulation and manufacturing IP barriers require the specific patent claim set from the Orange Book listing and/or patent publication files.

How does ORLADEYO compare with competing HAE prophylaxis drugs on market access and payer economics?

Commercial competition in HAE often turns on:

• Dosing convenience (oral vs injection)
• Patient preference and adherence
• Attack reduction and rescue medication use
• Total medical costs and utilization patterns (ER visits, short-term rescue)

A quantified comparison of payer economics and net price trajectory requires ORLADEYO and competitor contract data or at least public net sales plus competitor segment disclosure.

What is ORLADEYO’s financial trajectory: revenue growth, net sales, and margin structure?

A full financial trajectory analysis requires:

• ORLADEYO net sales history by period
• Geographic split (US vs ex-US)
• Channel mix (specialty pharmacy vs direct)
• Rebates and charge structures
• Management guidance and realized pricing

No complete financial metrics can be compiled here without the underlying financial statements, investor presentations, and/or audited net sales series.

What revenue exposure does ORLADEYO face from payer contracting, channel mix, and utilization risk?

In branded specialty drugs for rare diseases, revenue exposure is commonly tied to:

• Contract renewal cycles with PBMs and major plans
• Specialty pharmacy reimbursement dynamics
• Utilization management (PA denials and persistence requirements)
• Patient churn between prophylaxis modalities

A structured exposure forecast requires plan-level coverage data and net pricing trend data that are not included here.

What generic entry risks exist for ORLADEYO and how would they affect pricing?

If entry occurs:

• Price erosion typically follows a step-change after launch, with further erosion depending on subsequent competition and payer switching policies.
• Coverage restrictions can limit near-term substitution if branded retains preferred status or if payer committees insist on clinical criteria.
• Litigation outcomes determine timing and whether authorized generics or “at risk” launches appear.

Entry timing and probability cannot be stated without ORLADEYO patent expiry and litigation status.

Key takeaways

• ORLADEYO’s commercial outcome is shaped more by specialty payer access and adherence-driven switching in HAE prophylaxis than by broad-market demand.
• Financial trajectory risk hinges on the timing and enforceability of berotralstat’s patent exclusivity and any Paragraph IV litigation or settlement outcomes.
• A complete revenue shelf-life and competition scenario require the ORLADEYO Orange Book patent list with expiration dates, plus ANDA challenge and litigation/settlement data, and a historical net sales series.

FAQs

1. How do PBM formulary tiers typically affect ORLADEYO net pricing?
2. What historical specialty pharmacy purchasing patterns matter for berotralstat demand forecasting?
3. What litigation and settlement terms most often delay generic berotralstat entry?
4. How should investors model ORLADEYO revenue around exclusivity milestones?
5. What KPIs best predict ORLADEYO adoption in new HAE patient cohorts?

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References

1. FDA Orange Book. Therapeutic Equivalence Evaluations for ORLADEYO (berotralstat).
2. U.S. FDA prescribing information for ORLADEYO (berotralstat).
3. FDA ANDA Paragraph IV notice and litigation records for berotralstat (ORLADEYO).

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