FDA Advisory Committee votes in favour of the clinical benefit of Roche’s Polivy combination for people with previously untreated diffuse large B-cell lymphoma

2023-03-09

U.S. FDA’s Oncologic Drugs Advisory Committee voted 11 to 2 in favour of the clinical benefit of the phase III POLARIX study of Polivy in combination with R-CHP for people with previously untreated diffuse large B-cell lymphoma (DLBCL)
This is the first treatment in 20 years to show a significant and clinically meaningful improvement in progression-free survival over the standard of care for first-line DLBCL
DLBCL is an aggressive, hard-to-treat disease and the most common form of non-Hodgkin lymphoma in the US

Basel, 10 March 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 11 to 2 in favour of Polivy® (polatuzumab vedotin-piiq) in combination with Rituxan® (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of people with previously untreated diffuse large B-cell lymphoma (DLBCL). The ODAC provides the FDA with independent opinions and recommendations from outside medical experts though the recommendations are not binding. The FDA is expected to make a final decision on its review of the supplemental Biologics License Application (sBLA) for Polivy in this indication by 2 April 2023.

“Today’s committee decision to recognise the potential of this Polivy combination as a first-line treatment option is important since four in ten people with diffuse large B-cell lymphoma relapse or do not respond to initial treatment,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We believe the clinical benefit demonstrated in the POLARIX study may improve outcomes for many people with newly diagnosed DLBCL and look forward to continued collaboration with the FDA to make this treatment option available in the US.”

More than 60 countries have approved this Polivy combination for the treatment of adult patients with previously untreated DLBCL, including in the EU, UK, Japan, Canada and China. Polivy in combination with R-CHP was recently added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 1, preferred regimen for first-line DLBCL.

DLBCL is an aggressive, hard-to-treat disease and is the most common form of non-Hodgkin lymphoma in the US. Limited progress has been made in improving patient outcomes in previously untreated DLBCL over the last two decades. Polivy in combination with R-CHP is the first treatment in 20 years to show a significant improvement in progression-free survival (PFS) over the standard of care, MabThera/Rituxan in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in this setting.

The sBLA submission is based on pivotal data from the phase III POLARIX study, which demonstrated a statistically significant and clinically meaningful improvement in PFS with Polivy plus R-CHP compared to standard-of-care R-CHOP in first-line DLBCL. The risk of disease progression, relapse or death was reduced by 27% with Polivy plus R-CHP compared with R-CHOP (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; p<0.02). Safety outcomes were consistent with those seen in previous clinical trials, and 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%).

Polivy in combination with bendamustine and MabThera/Rituxan is currently approved in more than 80 countries worldwide for the treatment of adults with relapsed or refractory DLBCL after one or more prior therapies, including in the US under FDA accelerated approval, as a readily available, fixed-duration treatment option .

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-piiq) plus MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus MabThera/Rituxan, 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/Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of MabThera/Rituxan. The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. POLARIX is being conducted in collaboration with The Lymphoma Study Association and The Lymphoma Academic Research Organisation.

About diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.¹ DLBCL is an aggressive (fast-growing) type of NHL.¹ 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.^2,3 Approximately 160,000 people worldwide are estimated to be diagnosed with DLBCL each year^.⁴

About Polivy® (polatuzumab vedotin-piiq)
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. 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. Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

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®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin-piiq), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab) and Lunsumio® (mosunetuzumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies glofitamab, 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] Cancer.Net. Lymphoma –Non-Hodgkin: Subtype. [Internet; cited 2023 March]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes.
[2] 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.
[3] 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.
[4] Calculation for worldwide incidence: GLOBOCAN 2020. World Fact Sheet. [Internet; cited 2023 March]. Available from: http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.

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