BTK (Bruton Tyrosine Kinase) Inhibitors Market: Competitive Landscape, Pipeline, and Market Analysis 2023

Bruton Tyrosine Kinase (BTK) Inhibitors inhibit the BTK enzymes, which is a crucial element in the B cell signaling pathway that is used by particular B-cell receptor signaling pathways. B cell is a type of lymphocyte that has many immunoglobulins present on its surface. These immunoglobulins interact with other immunoglobulins and or antigens in the circulation. When the immunoglobulin attaches itself to the surface of the antigen and identifies it as a potential threat, it and T cells multiply into hundreds of cells. Activation of B cells induces BTK enzyme that communicates with other immune system cells and its proliferation. Therefore, inhibiting BTK can have several effects such as reducing cell migration, proliferation, and survival, as well as disrupting integrin-mediated adhesion to fibronectin, inhibiting DNA synthesis, diminishing cellular response to tissue homing chemokines (CXCL12, CXCL13, CCL19), and inducing apoptosis. Therefore, these reduce the proliferation of malignant B cells. These inhibitors are used for diseases associated with lymphocytes and are giving promising results with many candidates in clinical trials. Extensive research is being conducted globally to discover new and novel molecules to be used as BTK Inhibitors, like Calquence which is used for the treatment of Chronic Lymphocytic Leukemia (CLL). The development and launch of new products will thus increase the market’s revenue in the forecasted years. According to the American Cancer Society 2023 report, about 59,610 new leukemia cancer cases are to be reported in the USA, from which 18,740 new cases will be of CLL estimated to be nearly 1/4^th of leukemia cases. There has been a rise in the prevalence of leukemia for many years marking an opportunity for the market players globally.

A number of these inhibitors are in the market, while many are in ongoing clinical trials. 47 companies have various products in their pipelines, with 46 products in different stages of clinical trials. 2 products in Phase 4, 13 in Phase 3, 20 in Phase 2, and 13 in Phase 1 of the clinical trials.

Key Developments of BTK Inhibitors

• In February 2023, the EU approved the tablet formulation of Calquence (acalabrutinib) for treating Chronic Lymphocytic Leukemia (CLL) in adults.
• In August 2022, FDA approved Imbruvica (ibrutinib) for pediatrics older than one year with Chronic graft vs. host disease after failure of 1 or more lines of systemic therapy.
• In August 2022, FDA approved the tablet formulation of Calquence (acalabrutinib) for the treatment of adult patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and patients with relapsed or refractory mantle cell lymphoma (MCL), which is approved under accelerated approval.
• In November 2019, the EU approved Calquence (acalabrutinib) for treating Chronic Lymphocytic Leukemia (CLL) in adults.
• In November 2019, FDA approved Calquence (acalabrutinib) as a monotherapy treatment for the treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL).
• In 2023, the total revenue of the top three BTK inhibitors amounted to USD 9.7 billion, a slight dip from the previous year’s USD 9.8 billion. The primary reason for this decline is Ibrutinib (marketed as Imbruvica), which saw its sales drop from USD 8.7 billion (2021) to USD 5.9 billion by 2023. However, the blockbuster Zanubrutinib (known as Brukinsa) stood out amidst this trend. It contributed significantly to the overall revenue, raking in USD 1.3 billion in 2023.
• Beigene, the pharmaceutical company behind Zanubrutinib, is actively expanding its therapeutic indications beyond Chronic Lymphocytic Leukemia (CLL). Notably, on February 7, 2024, Zanubrutinib received approval in Canada for treating Relapsed or Refractory Follicular Lymphoma (FL) in combination with obinutuzumab. The molecule has already received approval for Waldenström's macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL) in Canada.

Approved Molecules Of BTK Inhibitors

• Imbruvica (Ibrutinib)
• Calquence (Acalabrutinib)

Drugs In The Pipeline Of BTK Inhibitors

• Brukinsa (Zanubrutinib)
• Yinuokai (Orelabrutinib)
• Remibrutinib (LOU064)
• Jaypirca (Pirtobrutinib)
• Rilzabrutinib (SAR444671)
• Evobrutinib (M2951)
• Tolebrutinib (SAR442168)
• Fenebrutinib (GDC-0853)
• Fujovee (Abivertinib)
• Edralbrutinib (TG-1701)
• Velexbru (Tirabrutinib)
• Sunvozertinib (DZD9008)
• M7583
• Branebrutinib (BMS-986195)
• Spebrutinib (CC-292)
• BMS-986142
• Nemtabrutinib (MK-1026)
• Poseltinib (HM71224)
• LP-168
• DTRMWXHS-12
• Atuzabrutinib (SAR444727)
• Elsubrutinib (ABBV-105)
• Elsubrutinib/Upadacitinib (ABBV-599)
• BIIB091
• JNJ-4681
• AC0058TA
• AS-1763
• DTRM-555
• HMPL-760
• TAK-020
• TAS5315
• TT-01488
• XNW1011
• Luxeptinib (CG-806)
• ABBV-992
• BIIB068
• CT-1530
• DWP213388
• GB5121
• HZ-A-018
• IMG-004
• MH048
• TQB3702
• Vecabrutinib (SNS-062)

Clinical Activity and Developments of BTK Inhibitors

As of July 2023, 47 companies have approximately 46 products for 66 diseases. For these diseases, 527 trials are being conducted by players globally. For instance,

• In May 2023, AstraZeneca completed a Phase 4 clinical trial to assess the safety and efficacy of acalabrutinib capsules in Indian adult patients with Chronic Lymphocytic Leukaemia (CLL) and relapsed and refractory Mantle Cell Lymphoma (MCL).
• Johnson & Johnson Pvt Ltd is conducting a Phase 4 clinical trial to assess the safety of Imbruvica (Ibrutinib Capsules 140 mg) in Indian patients with Chronic Lymphocytic Leukemia (CLL) or Mantle Cell Lymphoma (MCL) who have received at least one prior therapy or chronic lymphocytic leukemia with 17p deletion which was expected to complete by April 2023.
• BeiGene is conducting a Phase 3 clinical trial to compare the overall response rate of zanubrutinib versus ibrutinib in participants with relapsed/refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma that is expected to complete by September 2023.