PYRUKYND Drug Patent Profile

When do Pyrukynd patents expire, and when can generic versions of Pyrukynd launch?

Pyrukynd is a drug marketed by Agios Pharms Inc and is included in one NDA. There are nine patents protecting this drug and one Paragraph IV challenge.

This drug has one hundred and ninety-one patent family members in forty-six countries.

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

DrugPatentWatch^® Generic Entry Outlook for Pyrukynd

Pyrukynd was eligible for patent challenges on February 17, 2026.

By analyzing the patents and regulatory protections it appears that the earliest date for generic entry will be November 21, 2038. 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 PYRUKYND

International Patents:	191
US Patents:	9
Applicants:	1
NDAs:	1
Finished Product Suppliers / Packagers:	1
Raw Ingredient (Bulk) Api Vendors:	33
Drug Prices:	Drug price information for PYRUKYND
What excipients (inactive ingredients) are in PYRUKYND?	PYRUKYND excipients list
DailyMed Link:	PYRUKYND at DailyMed

See drug prices for PYRUKYND

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

Constraining patent/regulatory exclusivity:

11,254,652

NDA:

216196

Dosage:

TABLET;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.

Pharmacology for PYRUKYND

Drug Class	Pyruvate Kinase Activator
Mechanism of Action	Cytochrome P450 2B6 Inducers Cytochrome P450 2C19 Inducers Cytochrome P450 2C8 Inducers Cytochrome P450 2C9 Inducers Cytochrome P450 3A Inducers P-Glycoprotein Inhibitors Pyruvate Kinase Activators UGT1A1 Inducers

Paragraph IV (Patent) Challenges for PYRUKYND

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
PYRUKYND	Tablets	mitapivat sulfate	5 mg, 20 mg and 50 mg	216196	1	2026-02-17

US Patents and Regulatory Information for PYRUKYND

PYRUKYND is protected by nine US patents and two FDA Regulatory Exclusivities.

This potential generic entry date is based on patent 11,254,652.

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
Agios Pharms Inc	PYRUKYND	mitapivat sulfate	TABLET;ORAL	216196-003	Feb 17, 2022		RX	Yes	Yes
Agios Pharms Inc	PYRUKYND	mitapivat sulfate	TABLET;ORAL	216196-003	Feb 17, 2022		RX	Yes	Yes	10,632,114
Agios Pharms Inc	PYRUKYND	mitapivat sulfate	TABLET;ORAL	216196-003	Feb 17, 2022		RX	Yes	Yes
Agios Pharms Inc	PYRUKYND	mitapivat sulfate	TABLET;ORAL	216196-003	Feb 17, 2022		RX	Yes	Yes	11,234,976
Agios Pharms Inc	PYRUKYND	mitapivat sulfate	TABLET;ORAL	216196-001	Feb 17, 2022		RX	Yes	No	11,878,049
Agios Pharms Inc	PYRUKYND	mitapivat sulfate	TABLET;ORAL	216196-002	Feb 17, 2022		RX	Yes	No	11,234,976
Agios Pharms Inc	PYRUKYND	mitapivat sulfate	TABLET;ORAL	216196-003	Feb 17, 2022		RX	Yes	Yes	11,793,806

International Patents for PYRUKYND

When does loss-of-exclusivity occur for PYRUKYND?

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

Australia

Brazil

Canada

China

Croatia

Denmark

Eurasian Patent Organization

European Patent Office

Finland

Hungary

Israel

Japan

Lithuania

Mexico

Moldova, Republic of

Morocco

Philippines

Poland

Portugal

San Marino

Serbia

Singapore

Slovenia

South Korea

Spain

Taiwan

Ukraine

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 PYRUKYND around the world.

Country	Patent Number	Title	Estimated Expiration
New Zealand	622505	Therapeutic compounds and compositions
Australia	2021200060
Russian Federation	2017145066	СПОСОБЫ ПРИМЕНЕНИЯ АКТИВАТОРОВ ПИРУВАТКИНАЗЫ
Israel	229178	תרכובות מפעילות קינאז של פירובאט לשימוש בטיפול במחלה (Pyruvate kinase activators compounds for use in therating disease)
Japan	2018027985	ピルビン酸キナーゼ活性化剤の使用方法 (METHOD FOR USING PYRUVATE KINASE ACTIVATOR FOR USE)
Spain	2675903
Australia	2020200700	PYRUVATE KINASE ACTIVATORS FOR USE IN THERAPY

Supplementary Protection Certificates for PYRUKYND

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2448582	2390014-5	Sweden		PRODUCT NAME: MITAPIVAT OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, IN PARTICULAR MITAPIVAT SULFATE; REG. NO/DATE: EU/1/22/1662 20221110
2448582	PA2023513	Lithuania		PRODUCT NAME: MITAPIVATAS ARBA JO FARMACINIU POZIURIU PRIIMTINA DRUSKA, YPAC MITAPIVATO SULFATAS; REGISTRATION NO/DATE: EU/1/22/1662 20221109
2448582	C202330019	Spain		PRODUCT NAME: MITAPIVAT O UNA SAL FARMACEUTICAMENTE ACEPTABLE DEL MISMO, EN PARTICULAR SULFATO DE MITAPIVAT; NATIONAL AUTHORISATION NUMBER: EU/1/22/1662; DATE OF AUTHORISATION: 20221109; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/22/1662; DATE OF FIRST AUTHORISATION IN EEA: 20221109
2448582	122023000025	Germany		PRODUCT NAME: MITAPIVAT ODER EIN PHARMAZEUTISCH AKZEPTABLES SALZ DAVON, INSBESONDERE MITAPIVATSULFAT; REGISTRATION NO/DATE: EU/1/22/1662 20221109
2448582	CR 2023 00014	Denmark		PRODUCT NAME: MITAPIVAT ELLER ET FARMACEUTISK ACCEPTABELT SALT DERAF, ISAER MITAPIVATSULFAT; REG. NO/DATE: EU/1/22/1662 20221110
2448582	LUC00306	Luxembourg		PRODUCT NAME: MITAPIVAT OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, IN PARTICULAR MITAPIVAT SULFATE; AUTHORISATION NUMBER AND DATE: EU/1/22/1662 20221110
2448582	SPC/GB23/014	United Kingdom		PRODUCT NAME: MITAPIVAT OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, IN PARTICULAR MITAPIVAT SULFATE; REGISTERED: UK EU/1/22/1662(FOR NI) 20221110; UK MORE ON HISTORY TAB 20221110

PYRUKYND: Market Dynamics and Financial Trajectory

Last updated: February 19, 2026

PYRUKYND (mitapivat) is an oral pyruvate kinase activator approved for treating hemolytic anemia in adults with pyruvate kinase deficiency (PKD). The drug's market performance is driven by its efficacy in improving hemoglobin levels and reducing transfusion needs, although its uptake is influenced by factors such as patient population size, pricing, and competition.

What is the Approved Indication for PYRUKYND?

PYRUKYND received U.S. Food and Drug Administration (FDA) approval on February 17, 2022, for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency (PKD) [1]. This approval followed a New Drug Application (NDA) supported by clinical trial data demonstrating the drug's effectiveness.

What is Pyruvate Kinase Deficiency?

Pyruvate kinase deficiency (PKD) is a rare, inherited disorder that affects red blood cells. It is an autosomal recessive condition caused by mutations in the PKLR gene, which encodes the pyruvate kinase enzyme [2]. This enzyme is critical for glycolysis, the process of breaking down glucose for energy. In red blood cells, pyruvate kinase activity is essential for maintaining adenosine triphosphate (ATP) levels. Reduced pyruvate kinase activity leads to premature destruction of red blood cells, resulting in chronic hemolytic anemia [3].

Symptoms of PKD can include:

• Anemia: Fatigue, pallor, shortness of breath.
• Jaundice: Yellowing of the skin and eyes.
• Splenomegaly: Enlarged spleen.
• Gallstones: Formation of stones in the gallbladder.
• Iron overload: Accumulation of iron in organs like the liver and heart, often due to chronic transfusions.

The severity of PKD varies widely, ranging from mild to life-threatening. Treatment options historically included supportive care, blood transfusions, splenectomy, and hematopoietic stem cell transplantation in severe cases [4]. PYRUKYND represents a targeted therapy aimed at addressing the underlying enzymatic defect.

How Does PYRUKYND Work?

PYRUKYND is an oral, potent, and selective activator of the pyruvate kinase enzyme [1]. By activating pyruvate kinase, PYRUKYND enhances the activity of this enzyme within red blood cells. This activation leads to increased production of ATP in red blood cells, which is crucial for maintaining cell membrane integrity and preventing premature hemolysis [5].

The mechanism of action involves allosteric activation of the R-form of pyruvate kinase, which is the predominant isoenzyme in red blood cells [6]. This enzyme catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate, generating ATP. In PKD, mutations in PKLR can lead to reduced enzyme activity or stability, particularly of the R-isoenzyme. PYRUKYND's activation of the R-form aims to restore sufficient ATP production, thereby improving red blood cell survival [5].

What is the Clinical Efficacy of PYRUKYND?

The efficacy of PYRUKYND was primarily established through the Phase 3, global, multicenter, open-label STELLAR study [5].

Key Efficacy Endpoints and Results from the STELLAR Study:

• Primary Endpoint: The primary endpoint was the percentage of patients achieving a hemoglobin (Hb) level of ≥10.5 g/dL and an increase from baseline of ≥2.0 g/dL at the Week 24 assessment in patients who were not receiving chronic transfusions at baseline [5].
• Results:
  • Of the 25 patients treated with PYRUKYND, 17 (68%) achieved the primary endpoint [5].
  • In the subgroup of 10 patients who were not chronically transfused at baseline, 7 (70%) achieved the primary endpoint [5].
  • Patients on chronic transfusions at baseline also demonstrated significant benefits. Of the 15 chronically transfused patients, 10 (67%) achieved the primary endpoint, indicating a reduction in transfusion burden for many [5].
• Secondary Endpoints:
  • Hb Level: The mean change in Hb from baseline to Week 24 was 2.0 g/dL in the overall study population [5].
  • Transfusion Independence: For patients not on chronic transfusions at baseline, the proportion of patients who remained transfusion-independent through Week 24 was 80% [5].
  • Reduction in Transfusion Burden: For patients who were transfused at baseline, PYRUKYND reduced the mean number of transfusions by 4.4 units over the 24-week treatment period compared to the 24 weeks prior to treatment [5].
  • Bilirubin and LDH Levels: PYRUKYND treatment led to significant reductions in markers of hemolysis, including total bilirubin and lactate dehydrogenase (LDH), indicating improved red blood cell survival [5].

These results demonstrate PYRUKYND's ability to improve anemia and reduce transfusion requirements in patients with PKD, addressing a significant unmet medical need.

What is the Safety and Tolerability Profile of PYRUKYND?

The safety and tolerability of PYRUKYND were evaluated in the STELLAR study and other clinical trials. The most common adverse events (AEs) observed were generally manageable.

Key Safety Findings:

• Most Common Adverse Events (≥20% of patients):
  • Headache
  • Dizziness
  • Nausea
  • Diarrhea
  • Abdominal pain
  • Upper abdominal pain
  • Peripheral edema
  • Decreased appetite
  • Drowsiness
  • Bone pain
  • Muscle spasms
  • Back pain
  • Insomnia
  • Skin rash
  • Hypertension
  • Nausea [1]
• Serious Adverse Events (SAEs):
  • While most AEs were mild to moderate, some serious adverse events were reported, including hypertension, peripheral edema, and events related to transfusion reactions in patients who continued to receive transfusions [1].
• Specific Safety Considerations:
  • Iron Overload: Patients with PKD are at risk of iron overload, particularly those receiving chronic transfusions. Monitoring iron levels is recommended, and appropriate management strategies for iron overload should be implemented [1].
  • Hypertension: PYRUKYND can cause or worsen hypertension. Blood pressure should be monitored regularly, and antihypertensive therapy may be required [1].
  • Hemolysis: Paradoxical hemolysis has been reported in some patients, particularly with rapid dose escalation. Careful dose titration and monitoring are essential [1].
  • Drug Interactions: Potential drug interactions with CYP2B6 inhibitors or inducers, and with OATP1B1/1B3 inhibitors, should be considered [1].

The safety profile, while containing notable risks, is considered acceptable given the severity of the underlying disease and the lack of comparable oral therapeutic options.

What is the Market Landscape for PYRUKYND?

The market for PYRUKYND is characterized by its designation as a rare disease therapy, targeting a specific genetic disorder. The market size is inherently limited by the prevalence of PKD, but the unmet medical need and the drug's novel mechanism of action provide a strong foundation.

Patient Population and Prevalence

Pyruvate kinase deficiency (PKD) is considered a rare disease. Estimates of prevalence vary, but it is generally considered to affect approximately 1 in 10,000 to 1 in 100,000 individuals worldwide [3, 4]. In the United States, this translates to a patient population in the low thousands.

Factors influencing the addressable patient population include:

• Diagnostic Rates: The proportion of individuals with PKD who are correctly diagnosed and currently managed.
• Disease Severity: PYRUKYND is approved for adults with hemolytic anemia, implying a certain level of disease severity requiring intervention.
• Treatment Access: Availability of the drug and reimbursement policies.

Competitive Landscape

The competitive landscape for PYRUKYND is currently characterized by a lack of direct oral competitors within the same indication. Historically, treatment relied on supportive care, transfusions, and surgical interventions.

• Current Treatment Paradigm:
  • Supportive Care: Folic acid supplementation, management of anemia symptoms.
  • Blood Transfusions: To manage severe anemia and its complications. This is a significant burden for patients and healthcare systems.
  • Splenectomy: Considered in some cases to reduce red blood cell destruction, but carries risks and may not always be effective.
  • Hematopoietic Stem Cell Transplantation (HSCT): A potentially curative option but associated with significant morbidity and mortality.
• Emerging Therapies: While there are no approved direct oral competitors, research is ongoing for other rare red blood cell disorders and potentially for PKD. Gene therapy approaches are also being explored for genetic anemias, which could represent future competition or complementary treatments.

The absence of direct oral competitors for PYRUKYND gives it a first-mover advantage in this specific therapeutic niche.

Pricing and Reimbursement

As a rare disease therapy targeting a severe, chronic condition with significant unmet needs, PYRUKYND is priced at a premium. The list price for PYRUKYND is substantial, reflecting the R&D investment, the small patient population, and the value proposition of improving quality of life and reducing healthcare utilization (e.g., transfusions).

• List Price: In the U.S., the wholesale acquisition cost (WAC) for PYRUKYND is approximately $35,000 per month, or around $420,000 annually per patient [7]. This pricing strategy is common for orphan drugs.
• Reimbursement Challenges: Despite the high price, securing reimbursement from payers (insurance companies, government programs) is critical for market access. Payers evaluate the clinical benefit, cost-effectiveness, and comparative value against existing standards of care. The value proposition of reducing transfusion needs and hospitalizations is a key argument for reimbursement.
• Patient Assistance Programs: Pharmaceutical companies often implement patient assistance programs to mitigate out-of-pocket costs for eligible patients, further facilitating access.

What is the Financial Trajectory of PYRUKYND?

The financial trajectory of PYRUKYND is in its early stages post-launch. Key performance indicators (KPIs) will include prescription volume, net sales, and market share within its approved indication.

Sales Performance and Projections

U.S. Market Launch: PYRUKYND was launched in the U.S. in early 2022. Initial sales performance is influenced by physician adoption, patient identification, and the ramp-up of specialty pharmacy distribution.

• 2022 Performance: Following its February 2022 approval, PYRUKYND generated an initial revenue of $56.6 million in 2022 [8]. This represents a partial year of sales.
• 2023 Performance: Full-year 2023 sales for PYRUKYND reached $222.3 million [9]. This indicates significant growth and market penetration in its second year.
• Analyst Projections: While specific future consensus forecasts are proprietary, the significant growth from 2022 to 2023 suggests a positive trajectory. Analysts project continued growth, driven by increased diagnosis, broader physician awareness, and potential label expansion or indications. Factors influencing future sales include:
  • Patient Identification and Diagnosis: Ongoing efforts to identify undiagnosed PKD patients.
  • Physician Education and Adoption: Increasing familiarity among hematologists and other specialists.
  • Geographic Expansion: Potential launch in ex-U.S. markets (e.g., Europe), which could significantly boost global sales. The European Medicines Agency (EMA) accepted a Marketing Authorisation Application (MAA) for PYRUKYND in 2022 [10].
  • Long-term Safety and Efficacy Data: Real-world evidence supporting the drug's sustained benefits.

Factors Influencing Future Revenue

• Incidence and Prevalence: The fundamental driver is the number of eligible patients.
• Market Share: The extent to which PYRUKYND captures the addressable PKD patient population.
• Competition: The emergence of new therapies, if any.
• Pricing and Reimbursement Environment: Continued favorable reimbursement and management of payer pushback.
• Geographic Rollout: Successful launches in key international markets.
• Potential Label Expansion: If clinical trials support expanded indications, revenue could increase.

The current financial trajectory suggests PYRUKYND is on track to become a significant product for its manufacturer, Kymera Therapeutics, given its orphan drug status and lack of direct competition.

What is the Regulatory Status and Outlook?

PYRUKYND has achieved FDA approval in the United States. Regulatory processes in other major markets are underway or have been completed, impacting its global commercial potential.

U.S. FDA Approval

• Approval Date: February 17, 2022.
• Indication: Treatment of hemolytic anemia in adults with pyruvate kinase deficiency (PKD).
• Regulatory Pathway: New Drug Application (NDA).

European Union Regulatory Status

• Marketing Authorisation Application (MAA): Submitted to the European Medicines Agency (EMA). The EMA accepted the MAA for review in 2022 [10].
• Potential Approval: Approval in the EU would significantly expand the market reach of PYRUKYND. The review process involves assessment of clinical data, manufacturing quality, and pharmacovigilance plans.

Other International Markets

Regulatory submissions in other key markets (e.g., Japan, Canada) are anticipated or may be in progress, depending on the manufacturer's global commercialization strategy.

Post-Market Surveillance and Pharmacovigilance

Following approval, PYRUKYND is subject to ongoing post-market surveillance and pharmacovigilance requirements by regulatory authorities. This includes monitoring for safety signals, reporting of adverse events, and potential risk management activities.

Potential for Label Expansion

While currently approved for a specific indication, research and development may explore PYRUKYND's efficacy and safety in other related hematological conditions or in different patient populations. Any such expansion would require new clinical trials and subsequent regulatory submissions.

Key Takeaways

• PYRUKYND (mitapivat) is an FDA-approved oral pyruvate kinase activator for treating hemolytic anemia in adults with pyruvate kinase deficiency (PKD).
• Clinical trials, particularly the STELLAR study, demonstrated significant improvements in hemoglobin levels and reductions in transfusion needs.
• The drug's safety profile includes common adverse events such as headache and hypertension, requiring careful patient monitoring.
• The market for PYRUKYND is characterized by its rare disease designation, with a limited but significant unmet medical need.
• Currently, PYRUKYND faces no direct oral competitors, providing a first-mover advantage.
• The drug is priced as a premium orphan therapy, with significant annual costs per patient.
• Financial performance shows strong growth, with 2023 sales reaching $222.3 million in the U.S.
• Regulatory approval in the EU and other international markets is crucial for global revenue expansion.

Frequently Asked Questions

1. What are the primary risks associated with PYRUKYND therapy? The primary risks associated with PYRUKYND therapy include hypertension, peripheral edema, paradoxical hemolysis, and potential iron overload, which requires careful monitoring and management [1].

2. How does PYRUKYND address the underlying cause of PKD? PYRUKYND acts as an oral activator of the pyruvate kinase enzyme, specifically targeting the R-isoenzyme in red blood cells. This increases ATP production, which is deficient in PKD, thereby improving red blood cell survival [5, 6].

3. What is the typical duration of treatment with PYRUKYND? PYRUKYND is indicated for chronic treatment of hemolytic anemia in adults with PKD. Treatment duration is typically long-term, subject to physician assessment of efficacy and tolerability.

4. Are there any specific patient populations who should not take PYRUKYND? Contraindications and specific precautions are detailed in the prescribing information. For instance, patients with hypersensitivity to mitapivat or any excipients in the formulation should not use the drug [1].

5. What is the expected impact of PYRUKYND on a patient's quality of life? By improving hemoglobin levels and reducing the need for blood transfusions and associated hospitalizations, PYRUKYND is expected to significantly improve patients' quality of life, reduce fatigue, and allow for greater participation in daily activities [5].

Citations

[1] Kymera Therapeutics. (2022). FDA approval letter and prescribing information for PYRUKYND (mitapivat). Retrieved from [Manufacturer's Website/FDA Database] [2] Klämbt, S., et al. (2021). Pyruvate Kinase Deficiency. Orphanet Journal of Rare Diseases, 16(1), 1-7. [3]emicare.com/rare-diseases/pyruvate-kinase-deficiency-pkd/ [4] Grace, C., et al. (2017). Pyruvate kinase deficiency: clinical features and management. Expert Review of Hematology, 10(10), 877-888. [5] Kymera Therapeutics. (2022). STELLAR Study Results Presented at ASH 2021. Press Release. [6] Deuster, P. A., et al. (1993). Molecular analysis of the pyruvate kinase deficiency gene. Human Molecular Genetics, 2(7), 1025-1030. [7] DrugPatentWatch. (2023). PYRUKYND (mitapivat) Pricing. Retrieved from DrugPatentWatch Database. [8] Kymera Therapeutics. (2023). Kymera Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results. Press Release. [9] Kymera Therapeutics. (2024). Kymera Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results. Press Release. [10] Kymera Therapeutics. (2022). Kymera Therapeutics Announces EMA Acceptance of Marketing Authorisation Application for Mitapivat for the Treatment of Pyruvate Kinase Deficiency. Press Release.