Roche’s Polivy combination approved by European Commission for people with previously untreated diffuse large B-cell lymphoma

• First new treatment option in more than 20 years to show a clinically meaningful improvement in progression-free survival is approved for people with previously untreated diffuse large B-cell lymphoma (DLBCL)
• Approval is based on pivotal data from the phase III POLARIX study, where Polivy plus R-CHP significantly improved progression-free survival with comparable safety versus the standard of care, R-CHOP
• First-line treatment with Polivy plus R-CHP has the potential to reduce the burden on patients and healthcare systems, associated with disease progression¹

Basel, 25 May 2022 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission (EC) has granted approval of Polivy® (polatuzumab vedotin) in combination with MabThera®(rituximab) plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL).

DLBCL is an aggressive blood cancer and the most common form of non-Hodgkin lymphoma.² Each year in Europe, it is estimated that 40,000 people are diagnosed with DLBCL.3 While many patients are responsive to initial treatment, four out of ten are not cured with the current standard of care, and the majority of people who require subsequent lines of therapy have poor outcomes.⁴˒⁵ Most DLBCL relapses occur within 24 months of starting treatment and patients who remain progression-free 24 months following initiation of first-line therapy have favourable survival outcomes.⁴

“After more than 20 years with very limited treatment advances, the approval of Polivy plus R-CHP marks a new era for people battling this aggressive disease,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are delighted that the European Commission has approved this Polivy regimen and believe it has the potential to make a significant impact on the lives of people with DLBCL.”

“The approval of Polivy plus R-CHP in the first-line setting is great news for people in the EU diagnosed with this aggressive lymphoma, giving them a greater opportunity for positive outcomes,” said Professor Hervé Tilly, POLARIX Principal Investigator and Professor of Haematology at the University of Rouen. “Treatment with this regimen has been shown to reduce the chance of relapse and therefore need for subsequent treatments, limiting the burden of DLBCL.”

Today’s EC approval was based on results from the phase III POLARIX study (GO39942), the first trial to show a clinically meaningful improvement in progression free survival (PFS), compared to standard of care rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated DLBCL. All patients were followed for at least 24 months and at a median follow-up of 28.2 months, results of the study showed a 27% reduction in the risk of disease worsening or death with Polivy plus R-CHP compared to R-CHOP in first-line DLBCL (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; P<0.0177).⁶ The safety profile was comparable for Polivy plus R-CHP versus R-CHOP. The most frequently-reported (≥ 30%) adverse events with Polivy plus R-CHP were peripheral neuropathy (52.9%), nausea (41.6%), neutropenia (38.4%), and diarrhoea (30.8%).⁶ Results were presented for the first time in December 2021 at the 63rd American Society of Hematology Annual Meeting & Exposition and simultaneously published in the New England Journal of Medicine. The POLARIX study is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

In addition to today’s approval, the EC also converted Polivy's initial conditional marketing authorisation in the EU for the treatment of adult patients with relapsed or refractory DLBCL, who are not candidates for a haematopoietic stem cell transplant, to a full approval.

Roche continues to explore areas where Polivy has the potential to deliver additional benefit, including ongoing studies investigating combinations of Polivy with CD20xCD3 T-cell engaging bispecific antibodies in previously treated/untreated DLBCL.

About Polivy® (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies.⁷˒⁸ Polivy binds to cancer cells such as CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.⁹˒¹⁰ Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL. Polivy is currently marketed in the EU for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

About the POLARIX study
POLARIX [NCT03274492] is an international phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy® (polatuzumab vedotin) plus MabThera® (rituximab), cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma. Eight-hundred and seventy-nine patients were randomised 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by rituximab for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of rituximab. The primary outcome measure is progression-free survival (PFS) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goal of first-line therapy: decreasing the risk of disease worsening. 

About the LYSA and the LYSARC
The Lymphoma Study Association, or LYSA, is the internationally leading cooperative group for lymphoma research in Europe, conducting clinical studies ranging from the first tests of new medicines in humans to the establishment of reference therapeutic strategies. LYSA includes in its network more than 90 care centres distributed throughout three countries (France, Belgium, Portugal), and collaborates with many scientific teams at the international level.

The Lymphoma Academic Research Organisation, or LYSARC, is the LYSA operational structure that conducts clinical research projects on lymphomas at the international level.

About diffuse large B-cell lymphoma (DLBCL)
DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL. 2 DLBCL is an aggressive (fast-growing) type of NHL.2 While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.⁴˒⁵ Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.¹¹

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera® (rituximab), Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclyxto® (venetoclax) in collaboration with AbbVie, and Hemlibra® (emicizumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, and cevostamab, targeting both 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. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

About Roche 
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.

In recognizing our endeavor to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. 

Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. 

For more information, please visit www.roche.com.

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References
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[2] Cancer.Net. Leukemia – Lymphoma –Non-Hodgkin: Subtype. [Internet; cited 2022 May]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes.
[3] World Health Organization. GLOBOCAN 2020, Cancer Incidence and Mortality: IARC CancerBase No. 11 [Internet; cited 2022 May]. Available from: https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=cancer&mode_population=continents&population=900&populations=908&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=1&include_nmsc_other=1#collapse-group-1-4-0.
[4] Maurer MJ, Ghesquières H, Jais JP, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32(10):1066-1073.
[5] Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015;125(1):22-32.
[6] Roche. Polivy SmPC. European Medicines Agency. 
[7] Dornan D, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 2009;114:2721-29.
[8] Pfeifer M, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015;29:1578-86.
[9] Ducry L, et al. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem 2010;21:5-13.
[10] ADC Review. What are antibody-drug conjugates? [Internet; cited 2022 May]. Available from: https://adcreview.com/adc-university/adcs-101/antibody-drug-conjugates-adcs/.
[11] Globocan 2020. World Fact Sheet. [Internet; cited 2022 May]. Available from: http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.

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