Roche announced that Venclexta® (venetoclax) in combination with azacitidine has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with previously untreated intermediate, high- and very high-risk myelodysplastic syndromes (MDS) based on the revised International Prognostic Scoring System (IPSS-R). MDS are a rare group of blood cancers that gradually affect the ability of the bone marrow to produce normal blood cells. This can lead to weakness, frequent infections, anaemia and debilitating fatigue. In some cases, MDS can also progress into acute myeloid leukaemia (AML). Every year in the US, approximately 10,000 people are diagnosed with MDS, and the median survival for those with higher-risk MDS is approximately 18 months. This designation was granted based on interim results from the phase Ib M15-531 study investigating Venclexta/Venclyxto plus azacitidine in people with previously untreated, higher-risk MDS. BTD is designed to accelerate the development and review of medicines intended to treat serious or life-threatening conditions with preliminary evidence that indicates they may demonstrate a substantial improvement over existing therapies. This is the 38th BTD for Roche’s portfolio of medicines, and the 11th designation for its haematology portfolio. This most recent designation reinforces the potential of Venclexta/Venclyxto-based combinations across several blood cancers, including MDS. In the US, Venclexta has been granted six BTDs by the FDA: one for previously untreated chronic lymphocytic leukaemia (CLL), two for relapsed or refractory CLL, two for previously untreated AML, and one for MDS. Venclexta/Venclyxto is already approved in the US (as Venclexta) in combination with azacitidine, decitabine or low-dose cytarabine for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, and in the EU (as Venclyxto) in combination with hypomethylating agents, azacitidine and decitabine, for the treatment of adult patients with newly diagnosed AML who are ineligible for intensive chemotherapy. Venclexta/Venclyxto is also approved in the US and EU in combination with MabThera®/Rituxan® (rituximab) for the treatment of adult patients with CLL who have received at least one prior therapy; in combination with Gazyva®/Gazyvaro® (obinutuzumab) for the treatment of adult patients with previously untreated CLL; and as a monotherapy for the treatment of CLL in the presence of 17p deletion or TP53 mutation in people who are unsuitable for or have failed a B-cell receptor pathway inhibitor. MDS are a rare group of blood cancers that gradually affect the ability of the bone marrow to produce normal blood cells.2 This can lead to weakness, frequent infections, anaemia and debilitating fatigue. In some cases, MDS can also progress into acute myeloid leukaemia (AML).4,5 Every year in the US, approximately 10,000 people are diagnosed with MDS and the median survival for those with higher-risk MDS is approximately 18 months. There are several classifications of MDS – very low-risk to very high-risk – determined by the composition of the bone marrow, blood cell counts, and chromosomal alterations. Higher-risk disease is defined as intermediate, high- or very high-risk based on the revised International Prognostic Scoring System (IPSS-R), which is a risk assessment scale that uses five prognostic indicators to predict the course of a patient’s disease. Approximately half (45%) of patients present with higher-risk MDS, which is associated with a poorer prognosis and short life expectancy. The M15-531 [NCT02942290] study is a phase Ib, open-label, non-randomised, multicentre, dose-finding study evaluating Venclexta®/Venclyxto® (venetoclax) in combination with azacitidine in treatment-naïve patients with higher-risk myelodysplastic syndromes (MDS) comprising a dose-escalation portion and a safety expansion portion. The primary objectives of the study are to assess the safety profile and pharmacokinetics and determine the recommended phase II dose and dosing schedule of Venclexta/Venclyxto in combination with azacitidine. The response criteria specified in the M15-531 study are based on the modified International Working Group 2006 response criteria for MDS. Venclexta®/Venclyxto® (venetoclax) is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis. Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche group, in the US and commercialised by AbbVie outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood cancers. In the US, Venclexta has been granted six Breakthrough Therapy Designations by the U.S. Food and Drug Administration: one for previously untreated chronic lymphocytic leukaemia (CLL), two for relapsed or refractory CLL, two for previously untreated acute myeloid leukaemia, and one for myelodysplastic syndromes. Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; experience and knowledge in this therapeutic area runs deep. They are investing more than ever in effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, and Hemlibra® (emicizumab). pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, and cevostamab, targeting FcRH5 and CD3; Tecentriq® (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Scientific expertise, combined with the breadth of portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.