CHMP recommends EU approval of Roche’s Polivy combination

• Polivy plus R-CHP showed first clinically meaningful improvement in PFS with comparable safety in people with previously untreated diffuse large B-cell lymphoma (DLBCL) over the standard of care in more than 20 years
• Approximately 40% of people with previously untreated DLBCL are not cured with the current standard of care and face a poor prognosis [1,2]

• Recommendation is based on pivotal data from the phase III POLARIX study

Basel, 25 March 2022 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Polivy® (polatuzumab vedotin) in combination with MabThera® (rituximab) plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of previously untreated diffuse large B-cell lymphoma (DLBCL). Polivy plus R-CHP is the first treatment regimen to significantly improve outcomes in this disease in more than 20 years. A final decision regarding the approval of this Polivy combination is expected from the European Commission in the near future.

DLBCL is the most common form of non-Hodgkin lymphoma and it is estimated 40,000 people in Europe are diagnosed with the disease each year.[3,4] Approximately four out of ten patients will relapse after first line treatment and the majority of patients who require subsequent lines of therapy have poor outcomes.[1,2]

“A significant proportion of people newly diagnosed with diffuse large B-cell lymphoma, an aggressive form of blood cancer, do not respond adequately to existing therapies,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Therefore, more treatment options are needed that could increase a person’s chance of cure, and we look forward to bringing this new Polivy combination to people with DLBCL as soon as possible.”

The CHMP opinion was based on efficacy and safety data from the phase III POLARIX study (GO39942), comparing Polivy in combination with chemotherapy regimen R-CHP versus the standard of care MabThera plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in treatment of first-line DLBCL. The study showed significantly higher progression-free survival (PFS) versus R-CHOP after a median follow-up of 28.2 months (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; P<0.02).[5] PFS is a clinically meaningful disease-related outcome for people with previously untreated DLBCL and represents a goal of first-line therapy: decreasing the risk of disease worsening. The safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%), respectively.[5] 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.

Once approved, Polivy’s conditional marketing authorisation in the EU in combination with bendamustine plus MabThera, for the treatment of adult patients with relapsed or refractory DLBCL who are not candidates for a haematopoietic stem cell transplant will be converted to a full approval.

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.[6,7] Polivy binds to cancer cells such as CD79b and kills these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.[8,9] 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 MabThera, 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 MabThera for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of MabThera. 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 goals of first-line therapy: avoiding disease relapse, disease progression, and death. POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

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.[3] DLBCL is an aggressive (fast-growing) type of NHL.[3] While it is generally responsive to treatment in the frontline, as many as 40% of patients will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.[1,2] Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.[10]

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 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 recognising our endeavour 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.

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References
[1] 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.
[2] 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.
[3] Cancer.Net. Leukemia – Lymphoma –Non-Hodgkin: Subtype. [Internet; cited 2022 March]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes.
[4] World Health Organization. GLOBOCAN 2020, Cancer Incidence and Mortality: IARC CancerBase No. 11 [Internet; cited 2022 March]. 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.
[5] Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022;386(4):351-363. doi:10.1056/NEJMoa2115304.
[6] 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.
[7] 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.
[8] Ducry L, et al. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem 2010;21:5-13.
[9] ADC Review. What are antibody-drug conjugates? [Internet; cited 2022 March]. Available from: https://adcreview.com/adc-university/adcs-101/antibody-drug-conjugates-adcs/.
[10] Globocan 2020. World Fact Sheet. [Internet; cited 2022 March]. Available from: http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.

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