Dear Dr/ Prof.

We are pleased to notify that the VENCLEXTA has been registered in Israel!

VENCLEXTA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by a validated test, who have received at least one prior therapy.1

VENCLEXTA is included in the Israeli National Health Basket:1. For the treatment of chronic lymphocytic leukemia (CLL) refractory or relapsed patients with del 17p mutation, which have been previosly treated with Ibrutinib.2. The administration of VENCLEXTA, should be according to oncology or hematology expert prescription.2

VENCLEXTA is a first-in-class small molecule that targets BCL-2 to help restore the process of apoptosis. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. By binding directly to the BCL-2 protein, VENCLEXTA displaces pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases.1,3

VENCLEXTA monotherapy can cause rapid reduction in the disease burden, high overall response rate (ORR) of 77% and complete response (CR) of 18% in relapsed or refractory (R/R) CLL patients with 17p deletion.4,5

The responses are durable with median progression free survival (PFS) of 27.2 months for patients with 17p del.6

Potency of VENCLEXTA in achieving high-quality responses, such as MRD-negative CRs, even in the chemorefractory setting underscores the therapeutic potential of BCL-2 inhibition.7

VENCLEXTA, is a film-coated tablet with 3 dose options: 10mg, 50mg, 100mg. It should be taken orally once a day at the recommended daily dose. The Starting Pack provides the first 4 weeks of VENCLEXTA according to the ramp-up schedule. Once the ramp-up phase is completed, the 400mg dose is achieved using 100mg tablets supplied in bottles.1

License in Israel Venclexta

Indication and Important Safety Information

Venclexta, Venetoclax Tablets 10mg, 50mg,100mg

Indication VENCLEXTA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected a validated test, who have received at least one prior therapy. Important Safety Information Contraindication Concomitant of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated. Concomitant use of preparations containing St. John’s wort. Warnings and precautions: Tumor Lysis Syndrome; VENCLEXTA poses a risk for TLS in the initial 5-week ramp-up phase. Patients should be assessed for TLS risk, including evaluation of tumor burden and comorbidities, and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Concomitant use of VENCLEXTA with strong or moderate CYP3A inhibitors and P-gp inhibitors may increase the risk of TLS at initiation and during the ramp-up phase, and may require dose adjustment due to increases in VENCLEXTA exposure. Adverse Reactions: The most common adverse reactions (≥20%) of any grade were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue. The most frequent serious adverse reactions (≥2%) were pneumonia, febrile neutropenia, pyrexia, autoimmune hemolytic anemia (AIHA), anemia, and TLS. Drug Interactions: For patients who have completed the ramp-up phase and are on a steady daily dose of Venclexta, reduce the dose by at least 75% when used concomitantly with strong CYP3A inhibitors. Avoid concomitant use of moderate CYP3A inhibitors or P-gp inhibitors. If a moderate CYP3A inhibitors or P-gp inhibitors must be used, reduce the VENCLEXTA dose by at least 50%. Resume the VENCLEXTA dose that was used prior to initiating the CYP3A inhibitor or P-gp inhibitor 2 to 3 days after discontinuation of the inhibitor. Patients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain inhibitors of CYP3A. Avoid concomitant use of strong or moderate CYP3A inducers. Avoid concomitant use of narrow therapeutic index P-gp substrates. If these substrates must be used, they should be taken at least 6 hours before VENCLEXTA. Monitor international normalized ratio (INR) closely in patients receiving warfarin.

For full information please see Venclexta MoH approved Prescribing Information.

1. VENCLEXTA PRESCRIBING INFORMATION; March 2017. 2. Israeli National Health Basket notice, 2017. 3. Souers AJ, Leverson JD, Boghaert ER,et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nature Med. Feb 2013. 4. Seymour JF, Ma S, Brander DM, et al. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. Lancet Oncol. Jan 2017; 5. Roberts AW, Seymour JF, Eichhorst B, et al. Pooled Multi-Trial Analysis of Venetoclax Efficacy in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. 58th American Society of Hematology Annual Meeting and Exposition. Dec 2016; 3230. 6. Venclyxto SUMMARY OF PRODUCT CHARACTERISTICS (SmPC, 2016) 7. Tam CS, Seymour JF, Roberts AW. Progress in BCL2 inhibition for patients with chronic lymphocytic leukemia. Seminars in Oncology, (2016)

Abbvie Biopharmaceuticals Ltd. Israel at 4 Hacharash Street, Hod Hasharon 4524075. Tel: 09-7909600, Fax: 09-7909606

ILVE

N0517/0072

May 2017

רונית סטוביצקימנהלת תחום אונקולוגיה

אבווי ישראל

אינה קאןמנהלת רפואית- תחום אונקולוגיה

אבווי ישראל

בברכה,