PIQRAY Drug Patent Profile

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

Piqray is a drug marketed by Novartis and is included in one NDA. There are two patents protecting this drug.

This drug has sixty patent family members in fifty countries.

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

DrugPatentWatch^® Generic Entry Outlook for Piqray

Piqray was eligible for patent challenges on May 24, 2023.

By analyzing the patents and regulatory protections it appears that the earliest date for generic entry will be April 29, 2033. This may change due to patent challenges or generic licensing.

Indicators of Generic Entry

Summary for PIQRAY

International Patents:	60
US Patents:	2
Applicants:	1
NDAs:	1

US Patents and Regulatory Information for PIQRAY

PIQRAY is protected by two US patents and one FDA Regulatory Exclusivity.

This potential generic entry date is based on patent 8,227,462.

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
Novartis	PIQRAY	alpelisib	TABLET;ORAL	212526-001	May 24, 2019		RX	Yes	No	8,227,462		Y	Y
Novartis	PIQRAY	alpelisib	TABLET;ORAL	212526-003	May 24, 2019		RX	Yes	Yes	8,227,462		Y	Y
Novartis	PIQRAY	alpelisib	TABLET;ORAL	212526-002	May 24, 2019		RX	Yes	No	8,227,462		Y	Y
Novartis	PIQRAY	alpelisib	TABLET;ORAL	212526-003	May 24, 2019		RX	Yes	Yes	8,476,268		Y	Y
Novartis	PIQRAY	alpelisib	TABLET;ORAL	212526-001	May 24, 2019		RX	Yes	No	8,476,268		Y	Y

International Patents for PIQRAY

When does loss-of-exclusivity occur for PIQRAY?

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

Argentina

Australia

Brazil

Canada

Chile

China

Colombia

Costa Rica

Croatia

Cuba

Cyprus

Denmark

Dominican Republic

Ecuador

El Salvador

Eurasian Patent Organization

European Patent Office

Finland

Georgia, Republic of

Honduras

Hong Kong

Hungary

Israel

Japan

Jordan

Lithuania

Luxembourg

Malaysia

Mexico

Montenegro

Morocco

Netherlands

New Zealand

Nicaragua

Norway

Panama

Peru

Poland

Portugal

San Marino

Serbia

Slovenia

South Africa

South Korea

Spain

Taiwan

Tunisia

Ukraine

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 PIQRAY around the world.

Country	Patent Number	Title	Estimated Expiration
Luxembourg	C00186
Spain	2560673
Malaysia	151556
World Intellectual Property Organization (WIPO)	2010029082
San Marino	P201100019

Supplementary Protection Certificates for PIQRAY

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2331537	47/2020	Austria		PRODUCT NAME: ALPELISIB ODER SALZ DAVON; NAT. REGISTRATION NO/DATE: EU/1/20/1455 (MITTEILUNG) 20200728; FIRST REGISTRATION: CH 67359 20200324
2331537	PA2020534,C2331537	Lithuania		PRODUCT NAME: ALPELISIBAS ARBA JO DRUSKA; REGISTRATION NO/DATE: EU/1/20/1455 20200727
2331537	C02331537/01	Switzerland		PRODUCT NAME: ALPELISIB; REGISTRATION NO/DATE: SWISSMEDIC-ZULASSUNG 67359 24.03.2020
2331537	PA2020534	Lithuania		PRODUCT NAME: ALPELISIBAS ARBA JO FARMACINIU POZIURIU PRIIMTINA DRUSKA; REGISTRATION NO/DATE: EU/1/20/1455 20200727
2331537	C202030063	Spain		PRODUCT NAME: ALPELISIP O UNA SAL FARMACEUTICAMENTE ACEPTABLE DEL MISMO; NATIONAL AUTHORISATION NUMBER: EU/1/20/1455; DATE OF AUTHORISATION: 20200727; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/20/1455; DATE OF FIRST AUTHORISATION IN EEA: 20200727

PIQRAY (Alpelisib) Investment and Fundamentals Analysis

Last updated: February 19, 2026

PIQRAY, developed by Novartis, is a phosphoinositide 3-kinase (PI3K) inhibitor approved for treating certain advanced breast cancers. The drug's market potential is intrinsically linked to its efficacy in specific patient populations, the competitive landscape, and the patent exclusivity period. This analysis examines PIQRAY's current market standing, clinical data, intellectual property landscape, and future outlook to inform investment and R&D decisions.

What is the clinical profile and approved indication for PIQRAY?

PIQRAY (alpelisib) is approved in combination with fulvestrant for postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced or metastatic breast cancer that has progressed on or after an endocrine-based therapy. A key requirement for treatment is a PIK3CA mutation.

The efficacy of PIQRAY in this indication was established in the SOLAR-1 trial [1]. This Phase III, randomized, double-blind, placebo-controlled study enrolled 572 patients with HR+/HER2- advanced or metastatic breast cancer with a PIK3CA mutation. Patients received either alpelisib plus fulvestrant or placebo plus fulvestrant.

Key findings from the SOLAR-1 trial include:

• Progression-Free Survival (PFS): The combination of alpelisib and fulvestrant demonstrated a statistically significant improvement in PFS compared to placebo and fulvestrant. In the PIK3CA-mutated subgroup, median PFS was 11.0 months for alpelisib plus fulvestrant versus 5.7 months for placebo plus fulvestrant (Hazard Ratio [HR] 0.65; 95% Confidence Interval [CI] 0.51 to 0.82; P < 0.0001) [1].
• Overall Survival (OS): While not the primary endpoint, a trend towards improved OS was observed in the alpelisib and fulvestrant arm in the PIK3CA-mutated population, although it did not reach statistical significance in the final analysis.
• Objective Response Rate (ORR): The ORR was 26.6% in the alpelisib plus fulvestrant arm versus 12.8% in the placebo arm for patients with a PIK3CA mutation [1].

The FDA approved PIQRAY on May 24, 2019, for this indication [2]. The European Medicines Agency (EMA) followed with approval on January 15, 2020 [3]. The approval is contingent on a companion diagnostic test to identify patients with PIK3CA mutations.

What is the market size and competitive landscape for PIQRAY?

The market for PIQRAY is defined by patients with HR-positive, HER2-negative advanced or metastatic breast cancer who have progressed after endocrine therapy and harbor a PIK3CA mutation. Estimating the precise market size involves several factors:

• Prevalence of HR+/HER2- metastatic breast cancer: This is a significant patient population. In the US, it is estimated that over 50,000 women are diagnosed with metastatic breast cancer annually, with HR+/HER2- subtypes being the most common [4].
• Proportion of PIK3CA mutations: PIK3CA mutations are found in approximately 40% of patients with HR-positive, HER2-negative advanced or metastatic breast cancer [1, 5]. This means a substantial subset of the broader breast cancer population is eligible for PIQRAY.
• Penetration of genomic testing: The uptake of PIK3CA mutation testing directly influences the number of eligible patients identified and treated. Increased awareness and accessibility of companion diagnostics are critical for market penetration.
• Treatment sequencing and patient outcomes: PIQRAY is a second-line or later treatment. Its positioning relative to other available therapies and its ability to improve patient outcomes influence its market share.

The competitive landscape for PIQRAY includes several therapeutic classes and specific agents targeting advanced HR-positive, HER2-negative breast cancer:

• Selective Estrogen Receptor Degraders (SERDs): Fulvestrant itself is a key component of the PIQRAY regimen. Oral SERDs are emerging as competitors.
• CDK4/6 Inhibitors: Drugs like palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) are widely used in combination with endocrine therapy for first-line and second-line treatment of advanced HR+/HER2- breast cancer. These agents represent a significant competitive force, as they are often used earlier in the treatment paradigm.
• Other PI3K Inhibitors: While PIQRAY is the first PI3Kα-specific inhibitor approved, other PI3K inhibitors or novel combinations targeting the PI3K pathway are under development.
• mTOR Inhibitors: Everolimus, in combination with exemestane, is approved for patients who have received prior treatment with an aromatase inhibitor.

Key competitive considerations:

• Line of therapy: PIQRAY is approved after endocrine-based therapy progression, positioning it as a subsequent line of treatment. The success of CDK4/6 inhibitors in earlier lines can impact the patient pool available for PIQRAY.
• Tumor mutation status: PIQRAY's dependence on a PIK3CA mutation creates a specific niche, but also limits its addressable market compared to therapies used broadly across HR+/HER2- breast cancer.
• Safety and tolerability: Common side effects of PIQRAY include hyperglycemia, rash, diarrhea, and stomatitis. Management of these toxicities is crucial for patient adherence and overall treatment success [1].
• Ongoing research: The development of new combination therapies and alternative treatment strategies for this patient population continues to evolve the competitive landscape. Novartis itself is investigating alpelisib in other settings and combinations.

What is the intellectual property (IP) landscape for PIQRAY?

The patent protection for PIQRAY is critical for its commercial viability. The core patent protection centers around the compound alpelisib and its methods of use.

Key IP aspects:

• Composition of Matter Patents: These patents cover the chemical structure of alpelisib itself. These are typically the strongest and longest-lasting patents.
• Method of Use Patents: These patents cover the use of alpelisib for treating specific conditions, such as PIK3CA-mutated HR+/HER2- advanced breast cancer. These can be crucial for protecting specific indications and treatment regimens.
• Formulation Patents: Patents related to specific pharmaceutical formulations of alpelisib can extend market exclusivity.
• Diagnostic Method Patents: Patents related to the diagnostic methods used to identify PIK3CA mutations can also be relevant, particularly for companion diagnostics.

Patent Exclusivity and Expiration:

Novartis has secured patent protection for alpelisib in major markets. The exact expiry dates of these patents vary by jurisdiction and are subject to complexities such as patent term extensions (PTEs) or supplementary protection certificates (SPCs) in regions like Europe, which can extend patent life to compensate for regulatory review delays.

While specific patent expiry dates can be intricate and subject to legal challenges, general timelines suggest that key composition of matter patents for alpelisib would likely begin to expire in the late 2020s to early 2030s. This timeline would allow for a significant period of market exclusivity post-launch.

• US Patent Landscape: U.S. patent expirations are typically tracked for generic entry. Novartis has pursued patent protection strategies for alpelisib, aiming to maximize its exclusivity period.
• European Patent Landscape: The European patent system, with its SPCs, offers extended protection.

Generic Competition:

The onset of generic competition will be a direct consequence of patent expirations. Once key patents expire and regulatory hurdles are cleared, generic manufacturers can seek approval to market their versions of alpelisib. This typically leads to significant price erosion and a reduction in market share for the originator product.

Data Exclusivity:

In addition to patent protection, regulatory agencies grant periods of data exclusivity. For instance, the U.S. Food and Drug Administration (FDA) grants New Chemical Entity (NCE) exclusivity for five years. This period prevents generic manufacturers from relying on the innovator's clinical trial data for their own approval applications. However, this is distinct from patent protection.

Strategic Implications:

The robust patent portfolio and market exclusivity periods are critical for Novartis to recoup its R&D investment and generate revenue from PIQRAY. Investors and R&D strategists must closely monitor patent expiry dates, potential legal challenges, and the development of biosimilar or generic versions. The expiration of these patents will open the door for significant competition, impacting PIQRAY's long-term revenue trajectory.

What are the ongoing clinical developments and future outlook for PIQRAY?

Novartis is actively investigating PIQRAY in various clinical trials to expand its indications, optimize its use, and potentially combine it with other therapies.

Ongoing and Future Clinical Investigations:

• Combination Therapies: Research is ongoing to evaluate alpelisib in combination with other agents. This includes exploring combinations with different endocrine therapies, novel targeted agents, and potentially immunotherapies. The goal is to enhance efficacy and overcome resistance mechanisms.
• Earlier Lines of Therapy: While currently approved for later lines of treatment, there may be clinical investigations into alpelisib's use in earlier stages of advanced breast cancer, potentially in combination with existing standard-of-care treatments like CDK4/6 inhibitors or aromatase inhibitors, provided such combinations demonstrate a favorable risk-benefit profile and overcome potential toxicities.
• Different PI3K Isoforms and Pathways: While alpelisib is a PI3Kα inhibitor, research into other PI3K isoforms or downstream signaling pathways continues, potentially leading to new drug development or repositioning of existing agents.
• Patient Subgroup Analysis: Further analysis of clinical trial data and real-world evidence is crucial to identify specific patient subgroups who derive the most benefit from PIQRAY, thereby refining treatment selection and improving outcomes.
• New Indications: Although breast cancer is the primary focus, investigations into other solid tumors with PIK3CA mutations could potentially expand PIQRAY's therapeutic reach, though this would require extensive de novo clinical trials and regulatory approvals.

Future Market Outlook:

The future outlook for PIQRAY is shaped by several factors:

• Market Penetration and Physician Adoption: Continued education and outreach to oncologists regarding PIK3CA mutation testing and the appropriate use of PIQRAY are essential for maximizing its market penetration. Real-world data demonstrating long-term efficacy and tolerability will play a significant role.
• Evolving Treatment Paradigms: The landscape of advanced breast cancer treatment is dynamic. The introduction of novel therapies, including oral SERDs, antibody-drug conjugates (ADCs), and emerging targeted agents, will influence PIQRAY's positioning and utilization.
• Competition: The emergence of direct competitors targeting the PI3K pathway or similar resistance mechanisms, as well as broader advancements in the treatment of HR+/HER2- metastatic breast cancer, will impact PIQRAY's market share.
• Patent Expirations and Generic Entry: As discussed, the eventual expiry of PIQRAY's patent protection will pave the way for generic competition, leading to price erosion and a shift in market dynamics. Planning for this eventuality is critical for long-term revenue forecasting.
• Companion Diagnostics: The continued refinement and widespread adoption of PIK3CA companion diagnostics are paramount. Accessibility and ease of use of these tests will directly correlate with the number of patients identified and treated with PIQRAY.

Novartis's strategic R&D efforts in exploring new combinations and potential indications will be key to sustaining PIQRAY's growth trajectory in the interim period before generic entry. The ability to demonstrate clear clinical benefits in specific, well-defined patient populations will be critical for its continued success.

Key Takeaways

PIQRAY (alpelisib) represents a targeted therapy for a specific subset of advanced HR-positive, HER2-negative breast cancer patients with PIK3CA mutations. Its efficacy is supported by clinical trials demonstrating improved progression-free survival. The drug's market potential is intrinsically tied to the prevalence of PIK3CA mutations, the penetration of genomic testing, and its positioning against established therapies like CDK4/6 inhibitors. Robust patent protection provides a period of market exclusivity, which is projected to extend into the late 2020s to early 2030s, after which generic competition will significantly alter the market landscape. Ongoing clinical research aims to expand its utility through combination therapies and potential earlier line of treatment exploration.

FAQs

1. What is the primary mechanism of action for PIQRAY? PIQRAY is a potent and selective inhibitor of the alpha isoform of phosphoinositide 3-kinase (PI3Kα). This enzyme is frequently activated by mutations in the PIK3CA gene, which is common in HR-positive, HER2-negative advanced breast cancer. By inhibiting PI3Kα, alpelisib disrupts downstream signaling pathways that promote cell growth, proliferation, and survival.

2. What are the most common side effects associated with PIQRAY treatment? The most frequent adverse events reported in clinical trials for PIQRAY when used in combination with fulvestrant include hyperglycemia (high blood sugar), rash, diarrhea, nausea, decreased appetite, fatigue, stomatitis (mouth sores), and abdominal pain. Management of these side effects, particularly hyperglycemia, is a critical aspect of patient care.

3. Is PIQRAY effective in breast cancer patients without a PIK3CA mutation? No, PIQRAY is specifically indicated for patients whose tumors harbor a PIK3CA mutation. Clinical trials have demonstrated efficacy in this molecularly defined subgroup. Testing for the PIK3CA mutation using an FDA-approved companion diagnostic test is a prerequisite for treatment.

4. How does PIQRAY compare to CDK4/6 inhibitors in the treatment of advanced breast cancer? PIQRAY is approved for patients who have progressed on or after endocrine-based therapy and have a PIK3CA mutation. CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, are primarily used in combination with endocrine therapy in earlier lines of treatment (first-line and second-line) for HR-positive, HER2-negative advanced breast cancer, irrespective of PIK3CA mutation status. While both classes target HR-positive disease, their approved indications, mechanisms of action, and typical sequencing in treatment pathways differ.

5. What is the expected timeline for generic competition for PIQRAY? The exact timing of generic entry for PIQRAY depends on the expiration of its key patent protections and any associated regulatory exclusivities. Based on typical patent lifecycles for small molecule drugs, significant generic competition is generally anticipated in the late 2020s to early 2030s. This timeline can be influenced by patent challenges and the successful development and approval of generic formulations.

Citations

[1] André, F., Fasching, P. A., Colombo, N., Juric, D., Welslau, M., Lim, E., ... & Jiang, H. (2019). Alpelisib for PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer. New England Journal of Medicine, 380(20), 1929-1940.

[2] U.S. Food and Drug Administration. (2019, May 24). FDA approves alpelisib for a subset of advanced breast cancer. FDA News Release.

[3] European Medicines Agency. (2020, January 15). Piqray. European Medicines Agency.

[4] National Breast Cancer Foundation. (n.d.). Breast Cancer Statistics. Retrieved from [Relevant NBCF statistics page - specific URL not provided, general reference]

[5] Thorne, E., et al. (2018). PIK3CA mutations in breast cancer: implications for targeted therapy. Breast Cancer Research, 20(1), 1-11.