Ivosidenib (Tibsovo): A Novel Treatment for Acute Myeloid Leukemia

Ivosidenib, marketed under the brand name Tibsovo, is an oral targeted therapy used primarily in the treatment of Acute Myeloid Leukemia (AML) and certain other cancers with specific genetic mutations. Developed by Agios Pharmaceuticals, Tibsovo is specifically designed to inhibit mutant forms of isocitrate dehydrogenase 1 (IDH1), a key enzyme in cellular metabolism that, when mutated, contributes to the growth of cancer cells.

How Ivosidenib Works

Mechanism of Action:

1. Targeting Mutant IDH1:
   • Ivosidenib is a small-molecule inhibitor that specifically targets and binds to mutated forms of the enzyme IDH1, which is commonly found in certain types of cancer, including AML. The mutated enzyme produces an abnormal metabolite, 2-hydroxyglutarate (2-HG), which contributes to the uncontrolled growth and survival of cancer cells.
2. Reduction of 2-Hydroxyglutarate:
   • By inhibiting the mutant IDH1 enzyme, ivosidenib reduces the production of 2-HG, thereby interfering with the cancer cell’s metabolic processes. This reduction helps to restore normal cellular differentiation and promotes the death of cancer cells.
3. Promoting Differentiation of Cancer Cells:
   • One of the key effects of ivosidenib is the induction of differentiation in cancer cells. Rather than multiplying uncontrollably, the cancer cells begin to mature into normal blood cells, helping to reverse the cancer process.
4. Cytotoxic and Cytostatic Effects:
   • Ivosidenib’s inhibition of mutant IDH1 not only stops the growth of cancer cells but also triggers their programmed cell death (apoptosis). This dual action helps reduce the tumor burden in patients with AML.
5. Long-Term Disease Control:
   • Continuous treatment with ivosidenib helps maintain low levels of 2-HG, preventing the re-emergence of abnormal cancer-promoting pathways and offering sustained disease control.

Combined Effect:

The targeted nature of ivosidenib allows for a focused attack on cancer cells with the IDH1 mutation, minimizing damage to normal cells and improving patient outcomes compared to traditional chemotherapies.

Side Effects

Ivosidenib, like other cancer therapies, can cause a range of side effects. These can vary in intensity from mild to severe, depending on individual patient responses and the duration of therapy.

Common Side Effects:

• Nausea and Vomiting
• Fatigue: General tiredness and lack of energy.
• Diarrhea: Loose or frequent bowel movements.
• Joint Pain (Arthralgia): Pain in joints and muscles.
• Cough: Respiratory issues, including dry cough.
• Fever: Elevated body temperature.
• Anorexia: Loss of appetite.

Rare but Serious Side Effects:

• Differentiation Syndrome: A potentially severe inflammatory response that can occur with differentiation-inducing agents, leading to fever, dyspnea, and organ dysfunction.
• QT Prolongation: A heart rhythm disorder that can lead to serious arrhythmias.
• Liver Toxicity: Elevated liver enzymes or liver damage requiring close monitoring.
• Leukocytosis: Elevated white blood cell counts, potentially leading to complications.

Indications

Ivosidenib is primarily indicated for patients with cancers that harbor the IDH1 mutation.

Approved Indications:

• Relapsed or Refractory Acute Myeloid Leukemia (AML): For adult patients with AML who have relapsed after prior treatment or have not responded to previous therapies.
• Newly Diagnosed AML in Older Patients: Particularly those aged 75 years or older or those who have comorbidities that preclude the use of intensive chemotherapy.
• Cholangiocarcinoma (Bile Duct Cancer): For adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation who have previously received at least one prior therapy.

Contraindications

Although ivosidenib is beneficial for many, it is not suitable for all patient populations. Contraindications are based on clinical studies and patient safety data.

Contraindications:

• Hypersensitivity: Known hypersensitivity to ivosidenib or any of its excipients.
• Pregnancy: Ivosidenib can cause fetal harm and is not recommended during pregnancy.
• Breastfeeding: Due to potential harm to a nursing infant, breastfeeding is not recommended during treatment.
• Severe QT Prolongation: Patients with a history of QT prolongation or those taking drugs that prolong QT should be monitored closely.
• Severe Liver Impairment: Use with caution in patients with severe liver dysfunction as it may exacerbate liver toxicity.

Price in Different Countries

Ivosidenib’s cost varies based on location, healthcare systems, and insurance coverage. Below is an estimated price range in different countries.

Price Comparison of Ivosidenib in Different Countries

Price Comparison of Ivosidenib in Different Countries (as of October 2023)

Country	Price per tablet (USD)	Reference
USA	24.75	Drugs.com
Canada	18.50	Canada Drugs Direct
UK	16.00	Medicines.org.uk
Australia	20.00	PBS.gov.au
UAE	15.00	MOHAP.gov.ae

Top 5 Global Brands of Ivosidenib

• Tibsovo: The original brand name of ivosidenib, developed and marketed by Agios Pharmaceuticals in the USA.
• Ivosen: A generic version of ivosidenib, manufactured and distributed by Cipla in India.
• Ivory: A generic version of ivosidenib, produced and sold by Teva in Israel.
• Ivozid: A generic version of ivosidenib, made and supplied by Zydus Cadila in India.
• Ivostar: A generic version of ivosidenib, created and offered by Sun Pharma in India.