Film-coated tablets for the treatment of adults with acute myeloid leukaemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation or advanced metastatic bile duct cancer with an IDH1 R132 mutation

About the medicinal product

Tibsovo contains the active substance ivosidenib and is used to treat patients with certain cancers associated with a specific change (mutation) in a gene.

Tibsovo is used to treat adult patients with:

• newly diagnosed acute myeloid leukaemia (AML) in combination with a medicine containing the active substance azacitidine if the patients are not eligible for intensive chemotherapy. Treatment with the medicinal product Tibsovo is contraindicated in patients with acute promyelocytic leukaemia (APL).
• bile duct cancer (cholangiocarcinoma). Tibsovo is used as monotherapy for the treatment of patients whose bile duct cancer has spread to other parts of the body and for whom treatment with at least one other drug is no longer effective.

Tibsovo is used in patients whose AML or bile duct cancer is associated with mutation of the gene responsible for the production of the protein IDH1^[1] (IDH1 R132 mutation)

AML is a rapidly progressing blood cancer that is difficult to treat. It is one of the most common types of leukaemia in adults. Left untreated, AML quickly proves fatal in affected patients.

Bile duct cancer is also a life-threatening cancer with a poor prognosis.

No combination treatments targeted at IDH1 mutations are currently authorised in Switzerland for either of these diseases.

Since these cancers are rare, life-threatening diseases, the medicinal product Tibsovo has been authorised as an orphan drug. The term "orphan drug" is used to refer to important medicines for rare diseases.

^[1] _{IDH1: Isocitrate dehydrogenase-1 is an enzyme}

Mode of action

Modification of the gene that controls the production of the enzyme IDH1 disrupts the mechanism for forming healthy cells.

Degenerated cells can form as a result of the mutation of the enzyme IDH1 and potentially lead to the development of cancer.

Tibsovo blocks the mutated IDH1 enzyme and helps to slow or stop the cancer cells from growing.

Use

The medicinal product Tibsovo, containing the active substance ivosidenib, is subject to restricted medical prescription and is available as film-coated tablets in the dosage strength of 250 mg.

The doctor will confirm the presence of an IDH1 R132 mutation before starting the treatment and closely monitor the patients during the treatment.

The usual starting dose is 2 film-coated tablets (500 mg) once daily.

In addition to Tibsovo, patients with AML will also receive an intravenous medicine containing the active substance azacitidine.

The treatment should be continued until the cancer progresses. The doctor will discontinue the treatment if the patient suffers from side effects that make further treatment no longer appropriate.

Efficacy

AML

The efficacy of Tibsovo was investigated in a placebo-controlled^[2] clinical study (AG120-C-009) with 146 adult patients with previously untreated AML and an IDH1 mutation. The study participants did not satisfy the conditions for intensive chemotherapy. The patients received either 500 mg of Tibsovo or a corresponding placebo once daily in combination with azacitidine for 1 week every 4 weeks until the end of the study, disease progression, or the occurrence of serious side effects.

The study showed that the median^[3] overall survival (OS) was higher in the patients treated with Tibsovo than in those taking the dummy drug. An updated analysis of OS confirmed the benefit of Tibsovo in combination with azacitidine in terms of overall survival compared to placebo in combination with azacitidine, with median OS rates of 29.3 and 7.9 months, respectively.

Bile duct cancer

The efficacy of Tibsovo was investigated in a placebo-controlled clinical study (AG120-C-005) with 185 adult patients with locally advanced or metastatic bile duct cancer with an IDH1 R132 mutation, whose disease had progressed following at least 1, but no more than 2, prior treatments.

The study participants received either 500 mg of Tibsovo once daily or a placebo until disease progression or the occurrence of serious side effects.

The study showed that the time to recurrence of the cancer in the patients treated with Tibsovo was significantly longer than in patients in the placebo group.  

An updated OS analysis at the end of the data collection showed a median OS of 10.3 months for Tibsovo compared to 7.5 months for placebo.

^[2] _{Placebo: dummy drug}

^[3] _{Median: the value that lies exactly in the middle of a distribution of data is called the median or central value. One half is always less than the median, while the other half is always greater.}

Precautions, undesirable effects & risks

Tibsovo must not be used in those who are hypersensitive to the active substance or any of the excipients.

AML

The most common undesirable effects (affecting more than 1 in 10 users) are fatigue, vomiting, ECG changes, insomnia, headache, joint pain, dizziness, back pain, nosebleed, and a decreased white blood cell count.

Patients may also experience a serious side effect called differentiation syndrome, which can be life-threatening if left untreated.

Bile duct cancer

The most common undesirable effects (affecting more than 1 in 10 users) are fatigue, nausea and vomiting, diarrhoea, abdominal pain, decreased appetite, anaemia, headache, accumulation of fluid in the abdominal cavity, and rash.

All precautions, risks, and other possible undesirable effects are listed in the Information for patients (package leaflet) and the Information for healthcare professionals.

Why the medicinal product has been authorised

In the study with AML patients with an IDH1 R132 mutation, the overall survival was significantly prolonged in those who were treated with Tibsovo.

In the study with bile duct cancer patients with an IDH1 R132 mutation, recurrence of the cancer was delayed and overall survival prolonged in those who received Tibsovo.

Therefore, the treatment with Tibsovo represents an important therapeutic option for patients suffering from AML or bile duct cancer with the IDH1 R132 mutation.

Taking all the risks and precautions into account, and based on the available data, the benefits of Tibsovo outweigh the risks. Swissmedic has therefore authorised the medicinal product Tibsovo, containing the active substance ivosidenib, for use in Switzerland.

Further information on the medicinal product

Information for healthcare professionals:

Information for patients (package leaflet):

Healthcare professionals can answer any further questions.

^{The date of revision of this text corresponds to that of the SwissPAR. New information concerning the authorised medicinal product in question will not be incorporated into the Summary report on authorisation.}

^{Swissmedic monitors medicinal products authorised in Switzerland. Swissmedic initiates the necessary action in the event of newly discovered adverse drug reactions or other safety-relevant signals. New findings that could impair the quality, efficacy, or safety of this medicinal product are recorded and published by Swissmedic. If necessary, the medicinal product information is adapted.}