Anaplastic Lymphoma Kinase Metastatic Non-small Cell Lung Cancer - Market Insights, Epidemiology, and Market Forecast - 2034

Key Highlights:

• The total number of incident cases of ALK NSCLC in the US were ~10,130 in 2023.
• The total market size of ALK-mutated NSCLC in the 7MM was ~USD 1,526 million in 2023.
• Before 2011, patients with advanced NSCLC who were ALK-positive had few therapy choices. The usual course of treatment included chemotherapy. However, the discovery of the ALK driver mutation has significantly changed how this malignancy is treated, owing to the entry of targeted drugs for this subset.
• At present, ALECENSA and ALUNBRIG are the preferred first-line ALK TKIs. ALECENSA is much more widely used than ALUNBRIG and dominates the ALK market. Before the entry of ALECENSA and ALUNBRIG, XALKORI was the first-line treatment choice in ALK patients.
• There are not many companies at present attempting to target this segment. The pipeline of ALK NSCLC is not very robust.
• In February 2024, Nuvalent initiated the Phase II Portion of ALKOVE-1 Clinical Trial for Patients with ALK-Positive NSCLC and other Solid Tumors.
• In May 2024, the FDA granted breakthrough therapy designation (BTD) to NVL-655 for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who have been previously treated with two or more ALK tyrosine kinase inhibitors (TKIs).

According to the findings from the latest CROWN study, LORBRENA is superior to XALKORI as an initial treatment for people with advanced NSCLC that has changes in the ALK gene. After five years of follow-up data, 60% of the participants in the LORBRENA group were alive without the disease having worsened, compared with just 8% of those in the XALKORI group.

DelveInsight's "Anaplastic Lymphoma Kinase Metastatic Non-small Cell Lung Cancer - Market Insights, Epidemiology, and Market Forecast - 2034" report delivers an in-depth understanding of ALK Non-small Cell Lung Cancer, historical and forecasted epidemiology as well as ALK Non-small Cell Lung Cancer market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The ALK Non-small Cell Lung Cancer market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM ALK Non-small Cell Lung Cancer market size from 2020 to 2034. The report also covers current ALK Non-small Cell Lung Cancer 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

Anaplastic Lymphoma Kinase Metastatic Non-small Cell Lung Cancer Disease Understanding and Treatment Algorithm

ALK Non-small Cell Lung Cancer Overview

ALK refers to anaplastic lymphoma kinase, initially identified in lymphoma but predominantly associated with non-small cell lung cancer. The ALK gene is present during embryonic development and forms the gastrointestinal and nervous systems. It becomes inactive in utero, but in some individuals, it can re-activate and undergo fusion (joining) with another gene, resulting in an ALK fusion or ALK rearrangement that can lead to cancer. When ALK fuses with another gene and causes lung cancer, the patient is considered ALK-positive.

ALK can fuse with various genes, with the most common fusion partner being EML4. Even within EML4, multiple fusions exist based on the specific site where ALK joins the gene. Currently, the recommended treatment approach is generally uniform for most ALK-positive patients, irrespective of the precise type of ALK rearrangement they may have.

ALK Non-small Cell Lung Cancer Diagnosis

To determine if lung cancer is ALK-positive, testing of the tumor tissue or blood is required, employing various methods:

• FISH analysis: Examines chromosomal changes in tissue using microscopy.
• Immunohistochemistry: Detects cellular proteins via microscopy.
• Next-generation sequencing (comprehensive biomarker testing): Utilizes tumor tissue from a biopsy in a machine to identify numerous potential biomarkers simultaneously.
• Liquid biopsy: Searches for tumor DNA in the bloodstream.

ALK Non-small Cell Lung Cancer Treatment

Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patient's preferences and overall health. The most common treatments for ALK non-small cell lung cancer are:

Anaplastic Lymphoma Kinase Metastatic Non-small Cell Lung Cancer Epidemiology

The ALK Non-small Cell Lung Cancer epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by Total Incident Cases of NSCLC, Gender-specific Cases of NSCLC, Age-specific Cases of NSCLC, Total Incident Cases of ALK NSCLC, Total Incident Cases of NSCLC by Stage, and Total Cases of NSCLC by Genetic Mutations/Biomarkers in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2020 to 2034.

• About 10-15% of all lung cancers are SCLC, and about 80-85% are NSCLC. In the 7MM in 2023 ~ 524,000 NSCLC incident cases were present.
• Biomarker testing of ALK mutation is recommended in the 7MM and the biomarker testing rate is higher in the US compared to EU4 and the UK, and Japan.
• In 2023, there were nearly 10,000 cases of ALK NSCLC in the US, and are projected to increase during the forecasted period owing to the increase in biomarker testing rate.
• The total number of cases in EU4 and the UK for ALK NSCLC was estimated to be nearly 10,400 in 2023, and Germany accounted for the highest patient share among EU4 and the UK.

Anaplastic Lymphoma Kinase Metastatic Non-small Cell Lung Cancer Drug Chapters

The drug chapter segment of the ALK Non-small Cell Lung Cancer report encloses a detailed analysis of the marketed and the late-stage (Phase III and Phase II) pipeline drug. The marketed drugs segment includes ALECENSA (Genentech/Hoffmann-La Roche/Chugai Laboratories), ALUNBRIG (Takeda Pharmaceuticals), and others. Furthermore, the current key players for emerging drugs and their respective drug candidates include Xcovery (ensartinib), Nuvalent (NVL-655), and others. The drug chapter also helps understand the ALK Non-small cell lung cancer clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, and the latest news and press releases.

Marketed Drugs

ALECENSA: Genentech/Hoffmann-La Roche/Chugai Laboratories

ALECENSA (alectinib) is a highly selective, central nervous system-active oral medicine used to treat people with NSCLC whose tumors are identified as ALK-positive. ALECENSA is a tyrosine kinase inhibitor that targets ALK fusion proteins, preventing signaling within cancer cells to inhibit their growth and survival. It is an oral medicine created at Chugai Kamakura Research Laboratories.

The US FDA's approval of ALECENSA was based on the results of the Phase III ALEX study of ALECENSA in people with ALK-positive metastatic NSCLC who had not received prior treatment and the results of two Phase II studies, NP28761 and NP28673, of ALECENSA in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib. NCCN recommends ALECENSA for the first-line treatment of ALK NSCLC.

ALUNBRIG: Takeda Pharmaceuticals

ALUNBRIG (brigatinib) is a kinase inhibitor indicated for treating adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). ALUNBRIG is a tyrosine kinase inhibitor (TKI) with in vitro activity at clinically achievable concentrations against multiple kinases, including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in vitro and in vivo assays. Brigatinib also inhibited the in vitro proliferation of cell lines expressing EML4- ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK positive NSCLC xenograft growth in mice.

The median progression-free survival rates were 19.3 months with brigatinib and 19.2 months with alectinib in the Phase III ALTA-3 study for patients with ALK-positive non-small cell lung cancer.

Emerging Drugs

Ensartinib: Xcovery

Ensartinib is a potential best-in-class compound for the first-line treatment of ALK-positive NSCLC. Ensartinib has shown promising clinical activity in patients with ALK-positive NSCLC in a Phase I/II trial. A single-arm Phase II trial of ensartinib as second-line treatment for patients with ALK-positive NSCLC previously treated with crizotinib has been completed in 156 Chinese patients, and a New Drug Application has been filed in China. An ensartinib global first-line Phase III registration trial vs. crizotinib is ongoing. In March 2024, the FDA accepted the NDA, marking a key milestone for Xcovery in its mission to introduce ensartinib as a novel and distinct first-line therapeutic option.

NVL-655: Nuvalent

NVL-655 is a novel brain-penetrant ALK-selective inhibitor that overcomes several limitations observed with currently available therapies. NVL-655 remains active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R/L1196M ("GRLM"), G1202R/G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for brain penetrance to improve treatment options for patients with brain metastases. ALK-selectivity is emphasized to minimize CNS adverse events related to off-target inhibition of the structurally related tropomyosin receptor kinase (TRK) family and potentially drive more durable responses for patients with ALK-mutant variants. The ALKOVE-1 Phase I/II clinical trial of NVL-655 for patients with advanced ALK-positive NSCLC and other solid tumors is enrolling. In May 2024, the FDA granted breakthrough therapy designation (BTD) to NVL-655 for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who have been previously treated with two or more ALK tyrosine kinase inhibitors (TKIs).

Drug Class Insights

ALK rearrangements are present in around 5% of Non-Small-Cell Lung Cancer cases, primarily in adenocarcinomas, representing a distinct molecular subtype of lung cancer. The first ALK inhibitor approved for treatment was crizotinib, and subsequently, several other ALK inhibitors have received approval, including ceritinib, alectinib, brigatinib, and lorlatinib. A direct comparison among all the ALK TKIs is still lacking, but researchers are actively developing new ALK TKIs to overcome resistance to the currently available ones. This suggests the possibility of a sequential treatment strategy involving different ALK TKIs in this specific disease.

First generation ALK inhibitor: XALKORI was the first generation ALK inhibitor it showed better results than chemotherapy. XALKORI also had some limitations, such as its low penetration into the brain, which increased the risk of brain metastases, and its susceptibility to resistance, which reduced its effectiveness over time due to this second-generation ALK inhibitor emerged in the market and first was approved in 2017.

Second-generation ALK inhibitors: Such as ceritinib, alectinib, brigatinib, and others, effectively treat patients with ALK-positive NSCLC who have developed resistance to first-generation ALK inhibitors. These drugs showed higher potency and selectivity for ALK mutation, better penetration into the brain, and broader activity against different resistance mutations. They also had different safety profiles and side effects.

Third-generation ALK inhibitor: LORBRENA/LORVIQUA (lorlatinib) was approved in 2021 as third generation ALK inhibitor for the treatment of ALK-positive mNSCLC based on results from the CROWN trial in first line setting. It showed higher potency and selectivity for ALK mutation, better penetration into the brain, and broader activity against different resistance mutations.

Fourth-generation ALK inhibitor: NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors. NVL-655 is currently being investigated in clinical trials for treating patients with ALK-positive NSCLC who have developed resistance to second-generation ALK inhibitors.

American Society of Clinical Oncology (ASCO) May 2024

Anaplastic Lymphoma Kinase Metastatic Non-small Cell Lung Cancer Market Outlook

The treatment landscape of ALK-positive mNSCLC is constantly evolving. Targeted therapies are actively being developed as the understanding of the disease improves. Historically, ALK-positive mNSCLC was treated with chemotherapy alone and was associated with low 5-year survival rates. XALKORI (crizotinib) was the first drug to be approved for treating ALK-mutated NSCLC in 2011. Later, in 2017, the FDA approved ZYKADIA (ceritinib), the first-to-market second-generation TKI. Its PFS is not much better than chemotherapy, and major concerns were also noted, particularly gastrointestinal toxicity and some dosing issues.

ALUNBRIG (brigatinib), another first-line option, was approved by the FDA in 2020 based on results of the ALTA-1L (NCT02737501) trial, which compared brigatinib to crizotinib in patients with ALK-positive NSCLC who were refractory to crizotinib. Another next-generation ALK inhibitor approved by the FDA was LORBRENA/LORVIQUA (lorlatinib) in 2021 as a first-line therapy for patients with ALK-positive mNSCLC based on results from the CROWN (NCT03052608) trial.

The ALK market space become stagnant, and only a few players are developing therapies for ALK-mutated NSCLC. Some companies, such as Xcovery Holding Company (ensartinib) and Nuvalent (NVL-655), are exploring their assets in different clinical trials. Ensartinib is an ALK inhibitor already approved in China and is conducting a Phase III trial in the US for ALK-positive NSCLC. NVL-655 is a novel ALK inhibitor in the early development stage. These drugs may offer advantages over the existing ALK inhibitors, such as improved potency, selectivity, and safety. However, they face a competitive market with several approved drugs with proven efficacy and survival benefits. The ALK market needs more innovation and differentiation to attract new players and patients.

• In 2023, the total market size in the US for ALK non-small cell lung cancer was estimated to be nearly USD 915 million.
• Alectinib is a common second ALK TKI used after crizotinib progression in 1st line of treatment. In 2023 Alectinib captured ~60% market share of the ALK market in the US.
• There are few players in the emerging pipeline. Xcovery developed ensartinib, which is an ALK inhibitor already approved in China, and is conducting a Phase III trial in the US for ALK-positive NSCLC. Another is Nuvalent NVL-655, in the early stage of development.
• Lorlatinib is a third-generation ALK inhibitor. Lorlatinib generated ~ USD 250 million in 2023 in the 7MM.

Anaplastic Lymphoma Kinase Non-small Cell Lung Cancer Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2020-2034, which depends on the competitive landscape, safety, efficacy data, and order of entry. It is important to understand that the key players evaluating their novel therapies in the pivotal and confirmatory trials should remain vigilant when selecting appropriate comparators to stand the greatest chance of a positive opinion from regulatory bodies, leading to approval, smooth launch, and rapid uptake. Lorlatinib is a third-generation ALK inhibitor. It showed higher potency and selectivity for ALK mutation, better penetration into the brain, and broader activity against different resistance mutations compared to the previous generation ALK inhibitor. Its uptake is fast compared to alectinib. But by 2034 the highest market size is expected to be captured by alectinib.

Anaplastic Lymphoma Kinase Metastatic Non-small Cell Lung Cancer Activities

The report provides insights into therapeutic candidates in Phase III and II. It also analyzes key players involved in developing targeted therapeutics.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for small-cell Cell Lung Cancer emerging therapies.

KOL Views

To keep up with the real-world scenario in current and emerging market trends, we take opinions from Key Industry leaders working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on the evolving treatment landscape, patient reliance on conventional therapies, patient's therapy switching acceptability, and drug uptake along with challenges related to accessibility, including Medical/scientific writers, Medical Oncologists, Pulmonologists and Professors, Chief of the Thoracic Service at the Memorial Sloan Kettering Cancer Center, and Others.

Delveinsight's analysts connected with 40+ KOLs to gather insights; however, interviews were conducted with 18+ KOLs in the 7MM. Centers such as MD Anderson Cancer Center, Texas, UT Southwestern Medical Center in Dallas, Cancer Research UK Barts Centre in London, LUNGevity Foundation, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or ALK Non-Small Cell Lung Cancer market trends.

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 crucial 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 this clearly explains the drug's side effects 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

The cost of treating ALK Non-non-small cell Lung Cancer has shown significant increases over time, irrespective of the stage of the disease. According to real-world findings, this is particularly true for younger patients treated in the outpatient setting. There were apparent gaps in availability and/or reimbursement for ALK inhibitors.

In August 2018, ALECENSA was recommended, within its marketing authorization, as an option for untreated anaplastic lymphoma kinase (ALK)-positive advanced NSCLC in adults.

In January 2021, Brigatinib was recommended, within its marketing authorization, as an option for treating anaplastic lymphoma kinase (ALK)-positive advanced NSCLC that has not been previously treated with an ALK inhibitor in adults. Moreover, the next review is planned for 2024.

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

Scope of the Report:

• The report covers a segment of key events, an executive summary, and a descriptive overview of ALK Non-Small Cell Lung Cancer, explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight into the epidemiology segments and forecasts, the future growth potential of diagnosis rate, disease progression, and treatment guidelines has been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late-stage and prominent therapies will impact the current treatment landscape.
• A detailed review of the ALK Non-Small Cell Lung Cancer 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 and expert insights/KOL views, patient journey, and treatment preferences that help shape and drive the 7MM Non-Small Cell Lung Cancer market.

Anaplastic Lymphoma Kinase Metastatic Non-small Cell Lung Cancer Report Insights

• Patient Population
• Therapeutic Approaches
• ALK Non-Small Cell Lung Cancer Pipeline Analysis
• ALK Non-Small Cell Lung Cancer Market Size and Trends
• Existing and future Market Opportunity

Report Key Strengths

• Eleven Years Forecast
• The 7MM Coverage
• Non-Small Cell Lung Cancer Epidemiology Segmentation
• Key Cross Competition
• Conjoint analysis
• Drugs Uptake and Key Market Forecast Assumptions

Non-Small Cell Lung Cancer Report Assessment

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

FAQs:

• What is the historical and forecasted ALK Non-Small Cell Lung Cancer patient pool in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan?
• What was the ALK Non-Small Cell Lung Cancer total market size, the market size by therapies, market share (%) distribution in 2020, and what would it look like in 2034? What are the contributing factors for this growth?
• What are the advantages of novel fourth-generation ALK inhibitors over previous generations?
• What will be the impact of XALKORI's expected patent expiry?
• How will ALECENSA compete with other therapies in the first- and second lines?
• What are the pricing variations among different geographies for approved and off-label therapies?
• How would the market drivers, barriers, and future opportunities affect the market dynamics and subsequent analysis of the associated trends?
• Although multiple expert guidelines recommend testing for targetable mutations before therapy initiation, why do barriers to testing remain high?
• What are the current and emerging options for treating ALK Non-Small Cell Lung Cancer?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• Which ALK inhibitor generated the highest revenue by 2034?

Reasons to Buy:

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the ALK Non-Small Cell Lung Cancer Market.
• Insights on patient burden/disease prevalence, evolution in diagnosis, and factors contributing to the change in the epidemiology of the disease during the forecast years.
• 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.
• 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