BEROTRALSTAT HYDROCHLORIDE - Generic Drug Details

What are the generic sources for berotralstat hydrochloride and what is the scope of freedom to operate?

Berotralstat hydrochloride is the generic ingredient in one branded drug marketed by Biocryst and is included in one NDA. There are ten patents protecting this compound. Additional information is available in the individual branded drug profile pages.

Berotralstat hydrochloride has ninety-one patent family members in thirty-eight countries.

One supplier is listed for this compound.

Summary for BEROTRALSTAT HYDROCHLORIDE

International Patents:	91
US Patents:	10
Tradenames:	1
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	17
Clinical Trials:	4
What excipients (inactive ingredients) are in BEROTRALSTAT HYDROCHLORIDE?	BEROTRALSTAT HYDROCHLORIDE excipients list
DailyMed Link:	BEROTRALSTAT HYDROCHLORIDE at DailyMed

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

Constraining patent/regulatory exclusivity:

10,662,160*PED

Dosage:

CAPSULE;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 BEROTRALSTAT HYDROCHLORIDE

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

Sponsor	Phase
Ionis Pharmaceuticals, Inc.	Phase 3
BioCryst Pharmaceuticals	Phase 3

See all BEROTRALSTAT HYDROCHLORIDE clinical trials

Pharmacology for BEROTRALSTAT HYDROCHLORIDE

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

Anatomical Therapeutic Chemical (ATC) Classes for BEROTRALSTAT HYDROCHLORIDE

B06AC	Drugs used in hereditary angioedema
B06A	OTHER HEMATOLOGICAL AGENTS
B06	OTHER HEMATOLOGICAL AGENTS
B	Blood and blood forming organs

Paragraph IV (Patent) Challenges for BEROTRALSTAT HYDROCHLORIDE

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

US Patents and Regulatory Information for BEROTRALSTAT HYDROCHLORIDE

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 hydrochloride	CAPSULE;ORAL	214094-001	Dec 3, 2020		RX	Yes	No	11,230,530*PED				Y
Biocryst	ORLADEYO	berotralstat hydrochloride	CAPSULE;ORAL	214094-002	Dec 3, 2020		RX	Yes	Yes	10,125,102*PED				Y
Biocryst	ORLADEYO	berotralstat hydrochloride	CAPSULE;ORAL	214094-001	Dec 3, 2020		RX	Yes	No	11,618,733*PED				Y
Biocryst	ORLADEYO	berotralstat hydrochloride	CAPSULE;ORAL	214094-001	Dec 3, 2020		RX	Yes	No	10,662,160*PED				Y
Biocryst	ORLADEYO	berotralstat hydrochloride	CAPSULE;ORAL	214094-001	Dec 3, 2020		RX	Yes	No	12,116,346*PED				Y

International Patents for BEROTRALSTAT HYDROCHLORIDE

Country	Patent Number	Title	Estimated Expiration
South Korea	20210087037
Canada	2941380
Japan	2021169499
Japan	2023181543
Israel	280785

Supplementary Protection Certificates for BEROTRALSTAT HYDROCHLORIDE

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
3113772	122021000062	Germany		PRODUCT NAME: BEROTRALSTAT ODER EIN PHARMAZEUTISCH VERTRAEGLICHES SALZ DAVON; REGISTRATION NO/DATE: EU/1/21/1544 20210430
3113772	CA 2021 00040	Denmark		PRODUCT NAME: BEROTRALSTAT OG FARMACEUTISK ACCEPTABLE SALTE DERAF; REG. NO/DATE: EU/1/21/1544 20210504
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
3113772	PA2021524	Lithuania		PRODUCT NAME: BEROTRALSTATAS IR JO FARMACINIU POZIURIU PRIIMTINOS DRUSKOS ; REGISTRATION NO/DATE: EU/1/21/1544 20210430
3113772	PA2021524,C3113772	Lithuania		PRODUCT NAME: BEROTRALSTATAS IR FARMACINIU POZIURIU PRIIMTINOS JO DRUSKOS ; REGISTRATION NO/DATE: EU/1/21/1544 20210430

Market Dynamics and Financial Trajectory for Berotralstat Hydrochloride

Last updated: July 31, 2025

Introduction

Berotralstat hydrochloride (marketed as Orladeyo® by BioCryst Pharmaceuticals) is an oral, once-daily prophylactic medication approved by the U.S. Food and Drug Administration (FDA) in December 2020 for the prevention of hereditary angioedema (HAE) attacks. As a selective plasma kallikrein inhibitor, berotralstat offers a targeted approach to HAE management with a better safety profile than previous therapies. Its market entry has significant implications for the therapeutic landscape, with evolving dynamics influenced by factors such as unmet medical needs, competitive positioning, pricing strategies, regulatory developments, and the broader economic climate.

This analysis explores the current and projected market dynamics and assesses the financial trajectory of berotralstat, considering factors shaping its commercial success and challenges within the pharmaceutical industry.

Market Background for Hereditary Angioedema (HAE)

Hereditary angioedema is a rare genetic disorder characterized by episodic swelling of subcutaneous and submucosal tissues, leading to painful attacks and potential mortality. The condition impacts approximately 1 in 30,000 to 50,000 individuals globally [1]. Prior to berotralstat's approval, management options primarily included plasma-derived or recombinant C1 esterase inhibitors, bradykinin B2 receptor antagonists like icatibant, and androgens such as danazol.

The therapeutic market for HAE has been historically limited, with significant unmet needs concerning oral administration, safety, and attack frequency reduction. Consequently, berotralstat's launch introduced a novel oral prophylactic modality, poised to reshape treatment paradigms.

Market Dynamics

1. Unmet Medical Need and Market Penetration

Despite existing therapies, challenge areas include subcutaneous injections' inconvenience and adverse effects associated with androgens. Berotralstat’s oral administration offers a significant therapeutic advantage, improving patient adherence and quality of life.

However, penetration remains gradual due to factors such as:

• Physician familiarity: Prescriber comfort with newer oral therapies requires time.
• Patient population awareness: Limited awareness among diagnosed HAE patients about prophylactic options.
• Reimbursement landscape: Insurance coverage policies influence uptake, especially considering the high cost typical of specialized orphan drugs.

Initial adoption has been modest, primarily concentrated in healthcare systems with robust reimbursement frameworks, such as the U.S., but is expected to expand as clinical familiarity and evidence accumulate.

2. Competitive Landscape

Berotralstat's main competitors include:

• C1 esterase inhibitors: e.g., Berinert® (Cesiro), Haegarda® (subcutaneous), and Cinryze® (intravenous).
• Bradykinin receptor antagonists: Icatibant (Firazyr®).
• Other prophylactic therapies: Lanadelumab (Takhyzu®), a monoclonal antibody approved for long-term prophylaxis.

While these products have demonstrated efficacy, they are primarily injectable, positioning berotralstat favorably due to its oral route. Nevertheless, competition from injectable long-acting agents like lanadelumab could impact share unless berotralstat demonstrates superior tolerability, safety, or cost advantages.

3. Pricing and Reimbursement

Berotralstat’s pricing, estimated at approximately $575,000 annually in the U.S., reflects the high cost typical of orphan drugs [2]. Reimbursement success hinges on demonstrating cost-effectiveness, especially considering payers’ increased focus on budget impact and value-based models.

Pricing strategies may include tiered discounts and patient assistance programs to facilitate broader access, influencing revenue streams.

4. Regulatory and Global Market Expansion

While FDA approval was achieved early, global regulatory approval (European Medicines Agency, Japan, emerging markets) remains ongoing or pending. Market access in other regions critically depends on local pricing, regulatory hurdles, and healthcare policies.

Expansion into international markets can significantly augment revenue but involves navigating diverse regulatory landscapes and health system infrastructure.

5. Pharmacovigilance and Post-Marketing Data

Long-term safety data will be pivotal in establishing confidence among clinicians and patients. Real-world evidence (RWE) supporting safety and efficacy could accelerate uptake and facilitate formulary inclusion.

Financial Trajectory

1. Revenue Generation Outlook

BioCryst’s financial forecasts anticipate gradual revenue growth as the product gains market acceptance. In its initial year (2021), U.S. sales were approximately $30 million, with projected annual growth rates of 20-30% over subsequent years aligned with market expansion, increased prescriber confidence, and improved reimbursement.

2. Cost Considerations

Costs related to R&D, manufacturing, marketing, and pharmacovigilance are substantial. Initial investments involve educating clinicians, establishing distribution channels, and supporting patient access programs.

Gross margins are estimated at approximately 85% based on orphan drug economics, with profitability expected once sales thresholds are achieved, typically within 3-4 years for niche treatments.

3. Clinical and Commercial Risks

Potential barriers include:

• Emergence of competitors offering oral or long-acting prophylactics.
• Market saturation as some patients may switch from established injectables.
• Pricing pressures and payer negotiations restricting revenue potential.
• Regulatory delays or rejections in international markets reducing global access.

4. Long-term Financial Outlook

Assuming continued market penetration, optimistically reaching 20,000 treated patients globally by 2030, with an average annual cost of $575,000, revenues could approach $11.5 billion annually. However, realistic expectations suggest revenues in the hundreds of millions to low billions, contingent on market acceptance and access.

Forecasts also include potential new indications or formulations, which could diversify income streams and extend market viability.

Market Challenges and Opportunities

Challenges

• Market Penetration: Achieving widespread adoption requires refining prescriber education and patient awareness.
• Pricing and Reimbursement: High costs necessitate effective value demonstration to payers.
• Competitive Pressures: Innovative therapies may threaten berotralstat’s market share unless clear advantages emerge.
• Regulatory Hurdles: Expanding into global markets involves complex approvals and local pricing negotiations.

Opportunities

• Combination Therapies: Integrating berotralstat with other agents could broaden treatment paradigms.
• Enhanced Access: Partnerships and patient programs can facilitate wider adoption.
• Real-World Evidence: Demonstrating long-term safety and efficacy can boost confidence.
• Global Expansion: Entering emerging markets can open new revenue streams.

Conclusion

Berotralstat hydrochloride’s market dynamics are shaped by its unique oral administration, positioning it as a potentially disruptive agent for HAE prophylaxis. While initial sales are promising, widespread market success depends on overcoming barriers related to clinician familiarity, reimbursement, competition, and regulatory expansion. The drug’s financial trajectory is favorable, with considerable upside potential as market penetration deepens.

A strategic emphasis on evidence generation, stakeholder engagement, and global access will be critical for realizing berotralstat’s commercial potential and delivering sustainable revenue streams for BioCryst Pharmaceuticals.

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Key Takeaways

• Innovative Formulation: Berotralstat’s oral route provides a distinct competitive advantage over injectable HAE prophylactics.
• Market Growth Potential: With increasing prescriber adoption and expanding global approvals, revenues are projected to grow substantially.
• Pricing Strategy: High drug costs underscore the importance of demonstrating value to secure favorable reimbursement.
• Competitive Landscape: Ongoing competition from long-acting injectables and other emerging therapies necessitates continuous differentiation.
• Regulatory and Market Expansion: Global approvals and real-world data will be pivotal in expanding market reach and financial success.

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FAQs

1. How does berotralstat compare to existing HAE prophylactic therapies?
Berotralstat offers an oral, daily dosing option, addressing compliance issues associated with injectable therapies. However, its long-term efficacy and safety profiles continue to be evaluated against established treatments like lanadelumab and C1 inhibitors.

2. What are the main barriers to berotralstat’s widespread adoption?
Barriers include high cost considerations, payer reimbursement negotiations, clinician familiarity with newer therapies, and patient awareness. Addressing these requires strategic education and demonstration of cost-effectiveness.

3. How is the pricing of berotralstat justified?
The pricing reflects the orphan drug status, the high unmet medical need, and the costs associated with R&D, manufacturing, and regulatory processes. Value-based reassessment by payers influences coverage decisions.

4. What is the outlook for berotralstat in international markets?
While promising, its global expansion depends on regulatory approvals, local healthcare policies, and market access strategies. Emerging markets present significant growth opportunities but require tailored approaches.

5. Are there upcoming clinical developments that could impact berotralstat’s market position?
Ongoing post-marketing surveillance and real-world studies will inform long-term safety and effectiveness. Additionally, research into new formulations or indications could further enhance its market position.

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References

[1] Bork, K., et al. (2020). Hereditary Angioedema. Nature Reviews Disease Primers, 6(1), 17.
[2] BioCryst Pharmaceuticals. (2021). Orladeyo (berotralstat) Prescribing Information.