In short
Orelabrutinib is an investigational medicine that blocks Bruton's tyrosine kinase (BTK), a protein involved in certain immune cells and cancers. It is currently being studied in three authorised Phase 3 clinical trials with a combined enrollment of 2,281 participants. Two trials focus on progressive forms of multiple sclerosis (primary progressive and non-active secondary progressive), and one trial investigates treatment-naive mantle cell lymphoma.
Key points
- Orelabrutinib is a Bruton's tyrosine kinase (BTK) inhibitor being studied in three Phase 3 clinical trials.
- The largest trial enrolls 1,100 participants with non-active secondary progressive multiple sclerosis.
- A trial in primary progressive multiple sclerosis enrolls 705 participants and measures time to confirmed disability progression.
- A trial in treatment-naive mantle cell lymphoma enrolls 476 participants and measures progression-free survival.
- All three trials are currently authorised, meaning they are approved to begin or are ongoing.
- Orelabrutinib is given as oral tablets at doses of 80 mg or 150 mg depending on the condition studied.
What is orelabrutinib?
Orelabrutinib is a chemical substance classified as a Bruton's tyrosine kinase (BTK) inhibitor, a type of targeted therapy that belongs to the broader group of antineoplastic (anti-cancer) agents. It is also known by its development code ICP-022 and carries the ATC code L01EL04, which places it among BTK inhibitors used in cancer treatment. The substance is currently investigational, meaning it has not yet received marketing authorisation as a medicine. It is being studied in three authorised Phase 3 clinical trials for progressive forms of multiple sclerosis and for mantle cell lymphoma.
How does orelabrutinib work?
Orelabrutinib works by blocking the activity of Bruton's tyrosine kinase, an enzyme that plays a key role in the signalling pathways of B cells, a type of immune cell. BTK is involved in the B cell receptor signalling pathway and in the NF-kappa B signalling pathway, both of which contribute to the survival and activation of B cells. By inhibiting BTK, orelabrutinib may reduce the abnormal activity of B cells that is thought to contribute to autoimmune conditions such as multiple sclerosis, and it may also interfere with the growth of B-cell cancers such as mantle cell lymphoma. The substance also interacts with platelet activation pathways, which is relevant to how it may affect blood clotting.
Which conditions is orelabrutinib being studied for?
The clinical trials of orelabrutinib focus on three conditions:
- Primary progressive multiple sclerosis (PPMS) — a form of multiple sclerosis in which disability worsens steadily from the start, without clear relapses. One Phase 3 trial is testing whether orelabrutinib can delay disability progression in this condition.
- Non-active secondary progressive multiple sclerosis (SPMS) — a later stage of multiple sclerosis in which disability accumulates even without new inflammatory activity. A Phase 3 trial is evaluating orelabrutinib in this population.
- Treatment-naive mantle cell lymphoma (MCL) — a rare type of B-cell non-Hodgkin lymphoma in patients who have not yet received treatment. A Phase 3 trial is comparing orelabrutinib in combination with rituximab plus bendamustine against rituximab plus bendamustine alone.
How is orelabrutinib given?
Orelabrutinib is given by mouth as oral tablets. In the multiple sclerosis trials, the studied dose is 80 mg once daily, while in the mantle cell lymphoma trial the dose is 150 mg once daily. In the lymphoma trial, orelabrutinib is given in combination with two other medicines: rituximab, a monoclonal antibody, and bendamustine, a chemotherapy drug, both given intravenously. In the multiple sclerosis trials, orelabrutinib is compared with placebo tablets that match its appearance, shape, size, and weight.
What do the clinical trials show?
Orelabrutinib is being evaluated in three authorised Phase 3 clinical trials. Phase 3 is the stage of research in which a potential medicine is tested in large groups of people to confirm its effectiveness and monitor side effects. All three trials are currently authorised, meaning they have received regulatory approval to proceed or are already ongoing.
What are the trials measuring?
In the primary progressive multiple sclerosis trial, the main measure is the time to onset of composite confirmed disability progression (cCDP), which is defined as a worsening on any of three assessments: the Expanded Disability Status Scale (EDSS), the Timed 25-Foot Walk Test, or the 9-Hole Peg Test, confirmed over at least 12 weeks. In the non-active secondary progressive multiple sclerosis trial, the main measure is the time to onset of confirmed disability progression, confirmed over at least 24 weeks. In the mantle cell lymphoma trial, the main measure is progression-free survival (PFS), which is the length of time a person lives without their cancer getting worse, assessed by an independent review committee according to the 2014 International Working Group Criteria for Non-Hodgkin Lymphoma.
Who can take part in these trials?
The trials enroll specific patient groups. The primary progressive multiple sclerosis trial plans to enroll 705 participants with PPMS. The non-active secondary progressive multiple sclerosis trial is larger, with a planned enrollment of 1,100 participants with non-active SPMS. The mantle cell lymphoma trial plans to enroll 476 participants with treatment-naive mantle cell lymphoma, meaning they have not previously received treatment for their lymphoma.
What side effects are known?
The provided sources do not include detailed information on the side effects of orelabrutinib. As a BTK inhibitor, the substance may interact with platelet activation pathways, which suggests potential effects on blood clotting, but specific side effect data from these trials are not available in the supplied material.