Table 2.
Name, company, of some irreversible and reversible BTK inhibitors commercially disposable or under pre-clinical or clinical investigation
| Irreversible or Reversible BTKIs | Drug | Company (Trade name) | Clinical indication or pre-clinical trial investigation | Clinical Trials.gov number or FDA approved |
|---|---|---|---|---|
| Irreversible | Ibrutinib | (Imbruvica®) |
(i) Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and relapsed/refractory mantle cell lymphoma (MCL); (ii) Chronic graft-versus-host disease (cGVHD); (iii) COVID-19 treatment hospitalized patients; (iv) Refractory/relapsed autoimmune hemolytic anemia; (v) Anaphylaxis (food allergy); (vi) Aggressive systemic mastocytosis or mast cell leukemia |
(i) FDA approved in 2013; (ii) FDA approved in 2017; (iii) NCT04375397; (iv) NCT 04398459 and NTC 03827603; (v) NCT03149315; (vi) NCT 02415608 |
| Irreversible | Acalabrutinib | (Calquence®) |
(i) CLL, SLL, MCL; (ii) COVID-19 treatment hospitalized patients; (iii) Chronic graft-versus-host disease (cGVHD); (iv) Anti-MAG neuropathy mediated neuropathy; (v) Rheumatoid arthritis |
(i) FDA approved in 2017; (ii) NCT04497948 (study prematurely terminated), NCT04380688, NCT04346199; (iii) NCT04198922; (iv) NCT05065554; (v) NCT02387762 |
| Irreversible | Zanubrutinib | (Brukinsa®) |
(i) MCL; (ii) COVID-19 treatment hospitalized patients |
(i) FDA approved in 2019; (ii) NCT04382586; |
| Irreversible | Tirabrutinib | (Velexbru®) |
(i) CNS lymphoma, WM, CLL; (ii) Sjogren Syndrome; (iii) Rheumatoid arthritis |
(i) Approved in Japan; (ii) NCT03100942; (iii) NCT02626026; |
| Irreversible | Orelabrutinib | (?®) |
(i) Relapsed or refractory MCL; (ii) Phase I study for neuromyelitis optica spectrum disorder (iii) Phase 2 study for immune thrombocytopenia (ITP) (iv) Phase 2 study for relapsing–remitting Multiple Sclerosis |
(i) FDA approved in 2021 (for MCL); (ii) NCT05284175; (iii) NCT05020288; (iv) NCT04711148 |
| Irreversible | Evobrutinib | Merk® | (i) Relapsing–remitting multiple sclerosis | (i) NCT04032171 (terminated) and NCT04338061 (ongoing) |
| Irreversible | Spebrutinib | Avila Therapeutics/Calgene® | Pre-clinical studies | |
| Irreversible | Remibrutinib | Novartis® |
(i) Phase III for Chronic spontaneous urticaria; (ii) Allergy to Peanuts; (iii) Relapsing multiple sclerosis |
(i) Expanded access study NCT05170724; (ii) NCT05432388; (iii) NCT05147220 |
| Irreversible | Tolebrutinib | Sanofi®/Principia Biopharma® |
(i) Multiple sclerosis; (ii) Myasthenia gravis |
(i) NCT04742400; (ii) NCT05132569 |
| Irreversible | Olmutinib | Hamni Pharmaceuticals® | Non-small cell lung cancer |
NCT04510415 (terminated), NCT03228277, NCT02722161, NCT02444816, NCT02485652 (terminated) |
| Irreversible | Branebrutinib |
Bristol-Myers Squibb® |
(i) Atopic dermatitis; (ii) Rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren syndrome |
(i) NCT05014438 (recruiting); (ii) NCT04186871 (recruiting) |
| Irreversible | TAK-020 | Takeda® | Healthy volunteers | NTC02723201 and NCT02413255 (both completed) |
| Irreversible | Elsubrutinib | AbbVie® | Moderately to severely active systemic lupus erythematosus | NCT03978520 |
| Irreversible | Rilzabrutinib | Sanofi® |
(i) Chronic spontaneous urticaria; (ii) IgG4-related disease; (iii) Warm autoimmune hemolytic anemia wAIHA); (iv) Healthy volunteers (v) Atopic dermatitis; (vi) Immune thrombocytopenia; (vii) Asthma; (viii) Pemphigus |
(i) NCT05107115 (recruiting); (ii) NCT04520451 (recruiting); (iii) NCT05002777 (recruiting); (iv) NCT04748926 (completed); (v) NCT05018806 (recruiting); (vi) NCT04562766 (recruiting) (vii) NCT05104892 (proof of concept study, recruiting); (viii) NCT03762265 (terminated) |
| Reversible | Vecabrutinib | SNSS® | Lymphoid cancers | NCT03037645 (phase 1b, terminated) |
| Reversible | GNE-431 | Genetech® | Pre-clinical investigation | |
| Reversible | RN-489 | Roche® | Pre-clinical investigation | |
| Reversible | BMS-935177 |
Bristol-Myers Squibb® |
Pre-clinical investigation | |
| Reversible | BMS-986142 |
Bristol-Myers Squibb® |
(i) Rheumatoid arthritis; (ii) Sjögren syndrome |
(i) NCT02762123 (completed), NCT02456844 (completed); (ii) NCT02843659 (proof of concept study, terminated) |
| Reversible | GGI-1746 | GGI/Genetech® | Pre-clinical investigation | |
| Reversible | GDC-0834 | Gilead/Genetech® | Pre-clinical investigation | |
| Reversible | G-744 | Gilead/Genetech® | Pre-clinical investigation | |
| Reversible | G-278 | Gilead/Genetech® | Pre-clinical investigation (abandoned) | |
| Reversible | Fenebrutinib | Genetech |
(i) Relapsing multiple sclerosis; (ii) Healthy participants; (iii) Multiple sclerosis, primary progressive; (iv) Chronic spontaneous urticaria |
(i) NCT05119569, NCT04586010, NCT04586023 (all recruiting); (ii) NCT03596632 (completed) (iii) NCT04544449 (recruiting); (iv) NCT03693625 (terminated) |
cGVHD chronic graft-versus-host disease, CNS central nervous system, CLL Chronic lymphocytic leucemia, ITP immune thrombocytopenia, MAG myelin-associated, MCL relapsed/refractory mantle cell lymphoma, MZL marginal zone lymphoma, NCT National Clinical Trial, SLL small lymphocytic lymphoma, wAIHA warm autoimmune hemolytic anemia, WM Waldenström’s macroglobulinemia WM