Understanding Venclexta A Targeted Treatment for Blood Cancers

1. Understanding Venclexta: A Targeted Treatment for Blood Cancers Acute myeloid leukaemia (AML) is the most common type of acute leukaemia in adults. It mainly affects older adults, with the average age at diagnosis being 68 years.1 AML develops in the bone marrow when cells in the body start multiplying uncontrollably .2 This can lead to symptoms such as fatigue, weight loss, fever, night sweats and loss of appetite.3 For many years, especially in older patients or those unable to tolerate intensive treatment, the main options were palliative care or low-intensity therapies such as low-dose cytarabine or hypomethylating agents (e.g. azacitidine and decitabine). While these treatments provided some benefit, their effectiveness was often limited.1 A New Direction: Targeted Therapy in Cancer Recent advancements in cancer treatment have brought a shift toward targeted therapies – medications that can interfere with specific proteins that cancer cells need to survive.2 Unlike traditional chemotherapy, targeted therapies often spare healthy cells and work in a more precise way.4 One such promising drug is Venclexta, which has shown encouraging results in treating both AML and chronic lymphocytic leukaemia (CLL).5 What is Venclexta? Venclexta is a prescription medication used to treat certain types of blood cancer. It is approved for the treatment of AML and CLL.5 Depending on the type of cancer and the patient's treatment history, Venclexta may be used on its own or in combination with other medications such as5 • • • Obinutuzumab: for patients with untreated CLL Rituximab: for patients with CLL who have received at least one prior treatment Azacitidine or decitabine: for patient with AML who are not suitable for intensive chemotherapy Venclexta may also be used as monotherapy in patients with specific genetic mutations (such as 17p deletion or TP53 mutation) or in those whose cancer has been unresponsive to chemotherapy, immunotherapy and B‑cell receptor pathway inhibitors.5 What is the key ingredient in Venclexta? The active substance in Venclexta is venetoclax. It belongs to a class of medicines called B-cell lymphoma 2 (Bcl-2) inhibitors.5 How does Venclexta work? In leukaemia, cancer cells live longer than normal. This happens because of a protein called Bcl-2, which prevents these cells from dying as they normally would and makes them resistant to cancer medicines.5 As a result, the cancer cells accumulate and interfere with healthy blood cell production.6 Venclexta works by binding to the Bcl-2 protein, effectively blocking its function. This helps trigger death of cancer cells, slowing down the progression of the disease.5 How to take Venclexta?

2. Venclexta comes as a tablet that should be taken once a day with food. It must be prescribed and monitored by a healthcare professional experienced in cancer care.5 For CLL5: • Treatment begins with a low starting dose (20 mg). • The dose is gradually increased over 5 weeks to a maintenance dose of 400 mg daily. • The total length of treatment can vary depending on whether it is used alone or in combination with other drugs. For AML5: • Treatment starts at 100 mg, which is then increased over 3 days to reach 400 mg daily. • In AML, Venclexta is always used in combination with azacitidine or decitabine, and treatment is continued as long as it remains effective and tolerated. What are the common and serious side effects of Venclexta? Like all medicines, Venclexta can cause side effects. However, not everyone will experience them, and many can be managed with supportive care.5 Common side effects in CLL5: • • • • • • Pneumonia and nose and throat infection Low counts of white blood cells Anaemia and fatigue Nausea, vomiting, or diarrhoea High potassium and phosphate levels and low calcium levels Constipation, nausea, vomiting, diarrhoea and tiredness Common side effects in AML5: • • • • • Fever, pneumonia, urinary tract infections, or sepsis Low levels of white blood cells, red cells, or platelets Loss of appetite, dizziness, headache Gastrointestinal symptoms Joint pain, weakness, and weight loss Serious side effects requiring urgent medical attention5: • • • • Pneumonia Sepsis Neutropenia without fever Bleeding Always report any new or worsening symptoms to your doctor immediately. What other medication or therapy should I avoid? While taking Venclexta, it is important to avoid certain substances: • St. John’s Wort – a common herbal remedy used for anxiety and depression5

3. • Strong CYP3A inhibitors – these are certain medications that can increase the level of Venclexta in your body, especially during the early phase of treatment for CLL, especially during the early treatment period for CLL5,7 Your doctor will review your current medications to avoid harmful interactions. How to store Venclexta appropriately? Venclexta does not require any special storage conditions.8 How does Venclexta compare with other targeted therapies? Venclexta differs from therapies that target the B-cell receptor pathway in its mechanism – it specifically inhibits Bcl-2, a protein that helps cancer cells become resistant to chemotherapy. In patients with AML who show high Bcl-2 expression, Venclexta has shown promise.2 The drug is used in combination regimens, improving effectiveness without significantly increasing toxicity for patients.9,10 How to access Venclexta in India? Venclexta is not always available through regular retail pharmacies in India. However, patients can access it legally through the Named Patient Program (NPP).11 Steps to Access Venclexta in India: 1.Consultation with oncologist and confirmation for the medical need of Venclexta. 2.The doctor will submit a request to a licensed NPP provider. 3.The provider such as Rx4U will handle the regulatory approvals, importation, and delivery for smooth process. 4.Patient consent form and submission of basic documentation. 5.Upon approval, the drug is shipped directly to the hospital or pharmacy. NPP access may involve additional paperwork and cost considerations, so it is important to have a detailed discussion with your doctor or hospital pharmacy. Key Takeaway • Venclexta (venetoclax) is a targeted oral medicine used to treat CLL and AML. • It works by blocking the Bcl-2 protein, helping destroy cancer cells. • Venclexta is used alone or in combination with drugs like obinutuzumab, rituximab, azacitidine or decitabine. • Side effects are manageable but can include infections, low blood count and gastrointestinal symptoms. • In India, Venclexta can be accessed through a Named Patient Program. Frequently Asked Questions 1: Is Venclexta a form of chemotherapy? No, it is a targeted therapy, not a traditional chemotherapy drug.2

4. 2: How long will I need to take Venclexta? The treatment duration varies. It may be for a fixed period or continued as long as it works and is tolerated.5 3: Can I take Venclexta during fasting or on an empty stomach? No. Venclexta should always be taken with food.5 4: Can Venclexta cure my leukaemia? Venclexta is not considered a cure, but it can significantly reduce cancer cells.5 Note: The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment. Disclaimer: Rx4U procures prescribed medicines directly from manufacturers or authorized distributors. It does not claim ownership of any trademarks and complies with the provisions of the Trademark Act, 1999, particularly Sections 30 and 30(1) concerning ‘Fair Use’. It solely facilitates access to new launches through named patient import. References: 1.Pollyea DA, Amaya M, Strati P, Konopleva MY. Venetoclax for AML: changing the treatment paradigm. Blood Adv. 2019;3(24):4326-35. 2.What is acute myeloid leukemia. American Cancer Society. Updated March 4, 2025. Accessed June 25, 2025. https://www.cancer.org/cancer/types/acute-myeloid- leukemia/about/what-is-aml.html 3.Signs and symptoms of acute myeloid leukemia. American Cancer Society. Updated March 4, 2025. Accessed June 25, 2025. https://www.cancer.org/cancer/types/acute-myeloid- leukemia/detection-diagnosis-staging/signs-symptoms.html 4.Padma VV. An overview of targeted cancer therapy.Biomedicine (Taipei). 2015;5(4):19. doi:10.7603/s40681-015-0019-4 5.Venclyxto. European Medicines Agency. Updated September 20, 2024. Accessed June 25, 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/venclyxto 6.Saluja S, Bansal I, Bhardwaj R, Beg MS, Palanichamy JK. Inflammation as a driver of hematological malignancies.Front Oncol. 2024;14:1347402. doi:10.3389/fonc.2024.1347402 7.Bhatnagar S, Mukherjee D, Salem AH, Miles D, Menon RM, Gibbs JP. Dose adjustment of venetoclax when co-administered with posaconazole: clinical drug-drug interaction predictions using a PBPK approach.Cancer Chemother Pharmacol. 2021;87(4):465-474. doi:10.1007/s00280-020-04179-w 8.Venclyxto. Product information. AbbVie Deutschland GmbH Co. KG. 9.Pollyea DA, Pratz K, Letai A, et al. Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow-up from a phase 1b study.Am J Hematol. 2021;96(2):208-217. doi:10.1002/ajh.26039

5. 10.DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia.Blood. 2019;133(1):7-17. doi:10.1182/blood-2018-08-868752 11.Patil S. Early access programs: Benefits, challenges, and key considerations for successful implementation. Perspect Clin Res. 2016;7(1):4-8. doi:10.4103/2229-3485.173779