Phosphoinositide 3-kinase inhibitors (PI3K) - Target Population, Competitive Landscape, and Market Forecast - 2034

Key Highlights:

• Phosphoinositide 3-kinase (PI3K) inhibitors are a group of drugs that block the activity of PI3K enzymes, which are important for cell growth, survival, and metabolism. In many cancers, the PI3K pathway becomes overactive due to genetic mutations or other changes, leading to uncontrolled cell division and tumor growth.
• In cancer, mutations in PI3K genes (such as PIK3CA) or loss of tumor suppressors like phosphatase and tensin homolog (PTEN) can cause the PI3K pathway to be constantly active. By inhibiting PI3K, these drugs can slow down or stop the growth of cancer cells, trigger cell death (apoptosis), and sometimes make tumors more sensitive to other therapies.
• PI3K inhibitors have emerged as a promising therapeutic approach in the treatment of prostate cancer, lung cancer, breast cancer, ovarian cancer, glioblastoma cancer, and others.
• PI3K is a very well-validated target for cancer drugs, with five FDA-approved therapies in the class: ZYDELIG (idelalisib), ALIQOPA (copanlisib), COPIKTRA (duvelisib), PIQRAY (alpelisib), and UKONIQ (umbralasib).
• Currently, PIQRAY leads the market for PI3K inhibitors in HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer, mainly for solid tumors.
• The results presented at ASCO 2024 demonstrated that Inavolisib, when combined with endocrine therapy and a CDK 4/6 inhibitor, significantly slowed or halted cancer growth in patients with HR-positive, HER2-negative metastatic breast cancer who have a PIK3CA mutation. This promising development is expected to lead to FDA approval and provide a new treatment option for these patients.
• In January 2025, Kazia Therapeutics announced the launch of the ABC-Pax Phase 1b clinical trial, evaluating the combination of paxalisib with immunotherapy agents KEYTRUDA (pembrolizumab) or LYNPARZA (olaparib) in women with triple-negative breast cancer (TNBC).
• Key players in the PI3K inhibitors market include Gilead Sciences, Novartis, Roche/Genentech, Kazia Therapeutics, and others.
• In 2022, Gilead announced the voluntary withdrawal of U.S. indications for ZYDELIG (idelalisib) for follicular lymphoma and small lymphocytic leukemia.

DelveInsight's " Phosphoinositide 3-kinase inhibitors (PI3K) - Target Population, Competitive Landscape, and Market Forecast - 2034" report delivers an in-depth understanding of the PI3K inhibitors, historical and Competitive Landscape as well as the PI3K inhibitor market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The PI3K inhibitors market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM PI3K inhibitors market size from 2020 to 2040. The report also covers current PI3K inhibitors treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.

Geography Covered:

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2020-2034

PI3K Inhibitors Understanding

PI3K Inhibitors Overview

PI3K inhibitors are targeted cancer therapies designed to block the PI3K/AKT/mTOR pathway, a critical signaling cascade that regulates cell growth, survival, and metabolism. This pathway is tightly controlled in healthy cells but often becomes overactive in cancer due to genetic mutations or other alterations, leading to uncontrolled cell proliferation and tumor growth.

Classes of PI3K kinases

Class I PI3Ks are heterodimers with four isoforms (p110a, B, Y, δ) PIK3CA (p110a) is most often mutated in cancer.

Class II PI3Ks are monomers with three isoforms (C2a, C2B, C2Y) PI3KC2a is linked to breast cancer invasiveness.

Class III PI3Ks (VPS34) regulate autophagy and phagocytosis by forming protein complexes.

An important trend is the growing attention to solid tumors in the realm of PI3K inhibitors. While initially approved for hematological cancers, there's optimism that advancements in tolerability and efficacy might broaden their application to include solid tumors as well.

Further details are provided in the full report

PI3K Inhibitors Target Population

The PI3K inhibitors epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by target pool (Incident Cases by Indication, Eligible and Treatable Cases by Indication) in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2020 to 2034.

• In the 7MM, the highest eligible pool of promising indications for PI3K inhibitors in oncology was seen in the United States, followed by EU4 and the UK in 2024.
• As per DelveInsight, NSCLC accounted for ~ 204,900 incidence cases in the US in 2024.
• Among EU4 and the UK, Germany accounted for the highest number of PI3K Inhibitors Incident cases, while Spain accounted for the lowest number of cases.

PI3K Inhibitors Drug Chapters

The drug chapter segment of the PI3K inhibitors report encloses a detailed analysis of PI3K inhibitors marketed drugs and late-stage (Phase III and Phase II) pipeline drugs. It also helps understand the PI3K inhibitor's clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug and the latest news and press releases.

Marketed Drugs

ITOVEBI (inavolisib): Roche/Genentech

ITOVEBI is an investigational, oral targeted treatment with best-in-class potential that could provide well-tolerated, durable disease control and potentially improved outcomes for people with PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, who often have a poor prognosis and are in urgent need of new treatment options. ITOVEBI has been designed to help minimize the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and its unique mechanism of action that facilitates the degradation of mutated PI3K alpha.

In October 2024, the US FDA approved Genentech's ITOVEBI, a targeted treatment for advanced hormone receptor-positive, HER2-negative breast cancer with a PI3KCA mutation.

ZYDELIG (idelalisib): Gilead Sciences

ZYDELIG developed by Gilead Sciences is a first-in-class inhibitor of PI3K delta indicated for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

In January 2022, Gilead Sciences had voluntarily withdrawn ZYDELIG's indications for patients with relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma (SLL) who had undergone at least two prior systemic therapies.

Emerging Drugs

Paxalisib: Kazia Therapeutics

Kazia Therapeutics is developing paxalisib, a drug designed to penetrate the brain and block the PI3K/Akt/mTOR pathway. This drug is being developed to treat various types of brain cancer. Kazia licensed paxalisib from Genentech in late 2016. In 2021, a completed Phase II study in glioblastoma showed early signs that the drug might be effective. Currently, a major study called GBM AGILE is underway to test paxalisib in glioblastoma, with final results expected in the first half of 2024. Additionally, other clinical trials are testing paxalisib in brain metastases, diffuse midline gliomas, and primary CNS lymphoma. Some of these trials have already reported promising early results.

In January 2025, Kazia Therapeutics announced the launch of the ABC-Pax Phase 1b clinical trial, evaluating the combination of paxalisib with immunotherapy agents KEYTRUDA (pembrolizumab) or LYNPARZA (olaparib) in women with triple-negative breast cancer (TNBC).

Paxalisib received an Orphan Drug Designation (ODD) from the FDA for glioblastoma in February 2018, and Fast Track Designation (FTD) for glioblastoma in August 2020. It was also given Rare Pediatric Disease Designation (RPDD) and ODD for diffuse intrinsic pontine glioma (DIPG) in August 2020. Later, in June 2022 and July 2022, paxalisib was granted ODD for atypical teratoid/rhabdoid tumors. These designations help speed up the development and review of the drug for these serious conditions.

PI3K Inhibitors Market Outlook

The PI3K pathway is crucial in driving various cancers, and numerous PI3K-targeted therapies have been explored in oncology trials. This led to the regulatory approval of the isoform-selective inhibitor ZYDELIG for specific blood cancers, including relapsed/refractory (r/r) third-line chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and third-line follicular lymphoma. Although PI3K inhibitors have shown effectiveness in treating r/r CLL, their usage has been restricted due to the management complexities associated with PI3K inhibitor-related adverse events. For instance, ZYDELIG and COPIKTRA carry black box warnings for severe risks such as hepatotoxicity, diarrhea/colitis, pneumonitis, infections, and intestinal perforation.

There is an increasing focus on applying PI3K inhibitors to solid tumors. Initially approved for hematological cancers, these inhibitors are now being considered for solid tumors due to potential advancements in their tolerability and efficacy. Targeting the PI3Kδ isoform is particularly seen as a promising strategy for hematological malignancies.

The PI3K delta inhibitors landscape is rapidly evolving. Previously prominent treatments like ALIQOPA (copanlisib), COPIKTRA (duvelisib), and ZYDELIG (idelalisib) were used for relapsed follicular lymphoma, chronic lymphocytic leukemia, and small lymphocytic lymphoma. However, their market presence is declining because of significant adverse effects, including infections and liver toxicity, along with the emergence of more effective therapies.

At the September 2023 meeting of the UK Biochemical Society in Barcelona, experts discussed the PI3K pathway and suggested that advancing the understanding of PI3K biology and signaling could lead to a new era of PI3K-targeting drugs with novel mechanisms of action. Emerging therapies in the pipeline hold the potential to transform the drug approval market. As these new treatments advance, they could significantly change the available therapy landscape. Additionally, there is growing interest in combination therapies, which aim to enhance efficacy while reducing adverse effects. The future of PI3K inhibitors may be revitalized through innovative drug development and strategic combination regimens, better addressing the needs of patients with hematological malignancies.

PI3K Inhibitors Drugs Uptake

This section focuses on the uptake rate of potential approved and emerging PI3K inhibitors expected to be launched in the market during 2025-2034. The addition of inavolisib to the standard of care treatment significantly delayed disease progression in the first-line setting and has the potential to extend survival for people with metastatic breast cancers that harbor PIK3CA mutations.

PI3K Inhibitors Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I. It also analyzes key players involved in developing targeted therapeutics. The presence of numerous drugs under different stages is expected to generate immense opportunity for PI3K inhibitors market growth over the forecast period.

Pipeline development activities

The report covers information on designation, collaborations, acquisitions and mergers, licensing, and patent details for PI3K inhibitors emerging therapies. The increasing strategic collaborations among major market players to enhance the growth of their pipeline products are anticipated to drive market expansion.

KOL Views

To keep up with current and future market trends, we take Industry Experts' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry experts were contacted for insights on the PI3K inhibitor evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, drug uptake, along challenges related to accessibility.

DelveInsight's analysts connected with 30+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers such as MD Anderson Cancer Center, Cancer Research UK Barts Centre in London, and Rutgers University, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or PI3K inhibitors market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of gaps in disease diagnosis, patient awareness, physician acceptability, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided.

Conjoint Analysis analyzes multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.

In efficacy, the trial's primary and secondary outcome measures are evaluated; for instance, in event-free survival, one of the most important primary outcome measures is event-free survival and overall survival.

Further, the therapies' safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Market Access and Reimbursement

NICE Decision for PIQRAY (alpelisib)

Alpelisib plus fulvestrant is recommended as an option for treating hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced, or metastatic breast cancer in adults only if:

• Their cancer has progressed after a CDK4/6 inhibitor plus an aromatase inhibitor.
• The company provides alpelisib according to the commercial arrangement). There is a simple discount patient access scheme for alpelisib.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

ASCO 2024 Updates on PI3K Inhibitor

1. Roche presented additional analyses from first-line inavolisib/placebo + palbociclib + fulvestrant from INAVO120 Phase III randomized trial. INAVO120 met its primary endpoint, with a statistically significant and clinically meaningful improvement in PFS (15.0 months vs. 7.3 months)

2. In data presented during ASCO 2024, TQ-B3525 showed favorable efficacy and safety for relapsed/refractory follicular lymphoma patients after >=2 lines prior therapies. The ORR per independent review committee was 86.6%, with a complete response rate of 34.2%; this finding met the study's primary endpoint of ORR.

The abstract list is not exhaustive, and will be provided in the final report...

Scope of the Report:

• The report covers a segment of key events, an executive summary, and a descriptive overview of PI3K inhibitors, explaining their mechanism and applications in different indications.
• Comprehensive insight into the competitive landscape, forecasts, and future growth potential has been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late-stage and prominent therapies expected to impact the current treatment landscape.
• A detailed review of the PI3K inhibitor market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis expert insights/KOL views, and treatment preferences that help shape and drive the 7MM PI3K inhibitor market.

PI3K Inhibitors Report Insights

• PI3K Targeted Patient Pool
• PI3K Inhibitors Pipeline Analysis
• PI3K Inhibitors Market Size and Trends
• Existing and future Market Opportunity

PI3K Inhibitors Report key strengths

• Eleven years Forecast
• The 7MM Coverage
• Key Cross Competition
• Drugs Uptake and Key Market Forecast Assumptions

PI3K Inhibitors report assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT)

Key Questions:

• What was the PI3K inhibitors total market size, the market size by therapies, market share (%) distribution in 2024, and what would it look like in 2034? What are the contributing factors for this growth?
• Which drug is going to be the largest contributor in 2034?
• Which is the most lucrative market for PI3K inhibitors?
• Which indication accounts for maximum PI3K inhibitor sales?
• What are the pricing variations among different geographies for approved therapies?
• Do patients have any access issues that are driven by reimbursement decisions?
• What will be the growth opportunities across the 7MM concerning the patient population about PI3K inhibitors?
• What are the key factors hampering the growth of the PI3K inhibitor market?
• What are the recent novel therapies, targets, and technologies developed to overcome the limitations of existing therapies?
• What key designations have been granted for the emerging therapies for PI3K inhibitors?
• What is the cost burden of approved therapies on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved therapies?

Reasons to buy:

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the PI3K inhibitor market.
• Understand the existing market opportunities in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain) the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of indication-wise potential current and emerging therapies under the conjoint analysis section to provide visibility around leading indications.
• Highlights of access and reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet needs of the existing market so that the upcoming players can strengthen their development and launch strategy.