Cenrifki (tolebrutinib)
Cenrifki has been approved for the treatment of non-relapsing Secondary Progressive Multiple Sclerosis (nrSPMS) and to slow disability accumulation in the absence of relapse activity with Secondary Progressive Multiple Sclerosis (SPMS) in adults. Cenrifki contains the active ingredient tolebrutinib.
Cenrifki is approved for use in adults to:
- treat non-relapsing Secondary Progressive Multiple Sclerosis (nrSPMS)
- slow disability accumulation in the absence of relapse activity with Secondary Progressive Multiple Sclerosis (SPMS).
Multiple sclerosis (MS) is a chronic (long-term) condition that damages nerves in the central nervous system (brain and spinal cord).
In MS, the body’s immune system mistakenly damages the protective layer around nerves (called the myelin sheath) and causes inflammation. Breakdown of the myelin sheath stops the nerves from working properly and affects how signals travel around the body.
The most common form of MS is Relapsing Remitting MS (RRMS). In RRMS, people have periods of relapses (new or worsening symptoms) followed by periods of remissions (recovery or partial recovery).
The majority of people with RRMS transition to Secondary Progressive MS (SPMS). SPMS is a clinically more severe and disabling phase of the disease characterised by gradual and irreversible disability accumulation (worsening of symptoms). About 85 to 95% of people with SPMS have the non-relapsing form (nrSPMS), with fewer relapses and progressive disability accumulation over time.
Disability accumulation in MS can result from relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). However, growing evidence suggests that most disability accumulation is caused by progressive nerve damage that occurs independent of relapse activity.
Cenrifki is a Bruton’s tyrosine kinase (BTK) inhibitor. BTK inhibitors work by blocking the BTK enzyme to help stop abnormal activity of immune cells that contribute to MS development.
The exact way Cenrifki works in MS is not fully understood. Cenrifki appears to reduce the activity of certain immune cells (B cells, macrophages and microglia), in the brain, spinal cord and rest of the body to potentially limit inflammation and damage to nerves. This may slow disease progression and decline in daily functioning in MS.
Current treatments for MS generally aim to reduce relapses and slow disease progression (disease-modifying therapies), treat active relapses, and help manage symptoms. However, there are limited effective disease-modifying therapies for people with SPMS and nrSPMS.
The effectiveness and safety of Cenrifki were assessed in 3 clinical studies.
Study 1 assessed the effect of Cenrifki on confirmed disability progression (CDP) compared with placebo (a treatment with no active medicine) in 1,131 patients with nrSPMS. Disability progression was confirmed using a standard measure of disability and change over time in people with MS, called the Expanded Disability Status Scale (EDSS).
Studies 2 and 3 assessed annual relapse rates in patients with relapsing MS who received Cenrifki compared with those who received teriflunomide (a standard disease-modifying therapy). The results from studies 2 and 3 were combined (pooled) to assess other outcomes, including confirmed disability worsening (CDW), measured using the EDSS.
Key findings from the clinical studies
- Study 1 showed that Cenrifki was 31% more effective than placebo in reducing the risk of confirmed disability progression over 6 months.
- In study 1, more patients who received Cenrifki (8.6%) also showed confirmed disability improvement (CDI) over 6 months than those who received placebo (4.5%).
- Studies 2 and 3 did not meet their primary goal of improvement in relapse rates with Cenrifki compared with teriflunomide. However, combined results from studies 2 and 3 showed a 29% lower risk of confirmed disability worsening over 6 months in patients who received Cenrifki.
- The most common reported adverse event (problem or side effect) was COVID-19, as the clinical studies were conducted during the COVID-19 pandemic. Other adverse events were infections, petechiae (red or purple spots on the skin), abdominal pain, raised liver enzymes, increased tendency to bruise, and heavy menstrual bleeding.
- Serious liver injury has been reported in patients treated with existing registered BTK inhibitors and with Cenrifki in clinical studies.
Overall, the slowing of disability progression with Cenrifki was considered clinically meaningful, particularly given the unmet need for effective treatments for irreversible disability in nrSPMS.
The TGA decided that the application provided sufficient evidence to support the safety and effectiveness of Cenrifki and the medicine can be registered in Australia.
More detailed information on why the TGA approved Cenrifki will be published in the upcoming Australian Public Assessment Report (AusPAR).
For comprehensive information on potential side effects and risks, refer to the Consumer Medicine Information (CMI) leaflet or Product Information (PI) document.
This decision summary will not be updated to reflect any subsequent changes and may therefore not contain the most current information about the medicine. For the latest information, refer to the medicine’s CMI or PI.
The CMI leaflet offers guidance for consumers to support safe and effective use of the medicine. The CMI includes information on dose, how to use the medicine properly, potential side effects, safety precautions, storage instructions and more.
The Australian CMI for Cenrifki can be accessed through the searchable TGA eBusiness Services or ARTG databases.
The PI document provides essential prescribing information for health professionals, including details on dosage recommendations, pregnancy category, contraindications, precautions and potential side effects.
The Australian PI for Cenrifki can be accessed through the searchable TGA eBusiness Services or ARTG databases.
For health advice and information, including a symptom checker and service finder refer to the healthdirect website.
For advice on prescription medicines, over the counter medicines and other medicines (including complementary medicines) call Medicines Line.
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For data and reports on health and welfare topics in Australia refer to the Australian Institute of Health and Welfare website.
Treatment with Cenrifki should be started and supervised by a healthcare professional experienced in the management of MS.
As part of the approval process for Cenrifki, the sponsor company has put in place strict safety measures to reduce the risk of serious liver injury. These include clear guidance for prescribers on patient selection, a formal liver function monitoring program, and a boxed warning in the PI.
Refer to the PI for safety measures to be taken to reduce the risk of severe liver injury.