Roche’s Polivy combination reduced the risk of disease worsening or death by 27% in people with previously untreated aggressive form of lymphoma

Rhea-AI Summary

Roche announced promising results from the phase III POLARIX study, demonstrating that Polivy combined with R-CHP significantly improves progression-free survival by 27% for patients with previously untreated diffuse large B-cell lymphoma (DLBCL) compared to the standard R-CHOP therapy. This breakthrough marks the first substantial treatment advance for DLBCL in over 20 years. The trial involved 879 patients, with results presented at ASH 2021 and published in NEJM. Roche aims to expedite global availability of this potential treatment option.

Positive

• Phase III POLARIX study shows Polivy plus R-CHP reduces disease progression risk by 27%.
• First significant advancement in DLBCL treatment in over 20 years.
• Strong safety profile comparable to R-CHOP based on study results.

Negative

• None.

• Polivy plus R-CHP is the first treatment regimen to significantly improve outcomes in previously untreated diffuse large B-cell lymphoma in more than 20 years, potentially transforming treatment for people with this disease
• Four out of ten people receiving the current standard of care for this type of disease will see their cancer return after initial therapy
• Data were presented as a late-breaking abstract at ASH 2021 and simultaneously published in the NEJM
  
  

Basel, 14 December 2021 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from the phase III POLARIX study showing that treatment with Polivy® (polatuzumab vedotin) in combination with MabThera®/Rituxan® (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) significantly reduced the risk of disease progression, relapse or death (progression-free survival; PFS) by 27% compared with the current standard-of-care, MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Safety outcomes were consistent with those seen in previous trials and the safety profile was comparable for Polivy plus R-CHP versus R-CHOP.^1,2 Results were presented as a late-breaking abstract and during a press briefing at the American Society of Hematology (ASH) Annual Meeting and Exposition on Tuesday, December 14, 2021. Data from POLARIX were simultaneously published in the New England Journal of Medicine (NEJM). The study is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

“As many as 40% of people with this aggressive lymphoma experience a return of their cancer after initial therapy, at which point they face a poor prognosis and limited treatment options,” said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. “This Polivy-based regimen may conceivably change the disease course for many people with DLBCL, so we are working with health authorities around the world to make this important, potential new treatment option available as soon as possible.”

“DLBCL is an aggressive disease and, despite continuous research efforts, there have been limited treatment advances in the frontline setting in the past 20 years,” said Professor Hervé Tilly, POLARIX Principal Investigator and Professor of Haematology at the University or Rouen. “Results from the POLARIX trial represent an important advancement, bringing hope to people with this disease.”

First efficacy and safety data from the pivotal phase III POLARIX study showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP in patients with previously untreated DLBCL 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).^1,2 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. 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.^1,2 The POLARIX data form the basis of ongoing marketing applications to global health authorities.

Currently Polivy is used as an off-the-shelf, fixed-duration treatment option in the relapsed or refractory (R/R) DLBCL setting and is approved in combination with bendamustine and MabThera/Rituxan for the treatment of R/R DLBCL in more than 70 countries worldwide, including in the EU and in the United States. Roche continues to explore areas of unmet need where Polivy has the potential to deliver benefit, with ongoing studies investigating combinations of Polivy with the CD20xCD3 T-cell engaging bispecific antibodies mosunetuzumab and glofitamab, with Venclexta®/Venclyxto® (venetoclax), which is being developed by AbbVie and Roche, and with MabThera/Rituxan in combination with gemcitabine and oxaliplatin in the phase III POLARGO study.

Follow Roche on Twitter via @Roche and keep up to date with ASH 2021 news and updates by using the hashtag #ASH21.

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®/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 (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 120 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 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, making it a promising target for the development of new therapies.^3,4 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.^5,6 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 marketed in the US by Genentech as Polivy (polatuzumab vedotin-piiq), with piiq as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

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.⁷ DLBCL is an aggressive (fast-growing) type of NHL.⁸ 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.⁸ Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.⁹

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®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/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
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics, as well as growing capabilities in the area of data-driven medical insights help Roche deliver truly personalised healthcare. Roche is working with partners across the healthcare sector to provide the best care for each person.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. In recent years, the company has invested in genomic profiling and real-world data partnerships and has become an industry-leading partner for medical insights.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the thirteenth consecutive year, Roche has been recognised as one of the most sustainable companies in the pharmaceutical industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. 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.

All trademarks used or mentioned in this release are protected by law.

References
[1] Tilly H, et al. The POLARIX study: polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy in patients with previously untreated diffuse large B-cell lymphoma. Presented at: ASH Annual Meeting and Exposition; 2021 Dec 11-14. Abstract #LBA-1.
[2] Tilly H, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. New Eng J Med. 2021.
[3] 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.
[4] 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.
[5] Ducry L, et al. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem 2010;21:5-13.
[6] ADC Review. What are antibody-drug conjugates? [Internet; cited 2021 July]. Available from: https://adcreview.com/adc-university/adcs-101/antibody-drug-conjugates-adcs/
[7] World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press; 2008.
[8] Maurer JM, 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;32:1066-73.
[9] Globocan 2020. World Fact Sheet. [Internet; cited 2021 November]. Available from: http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf

Roche Group Media Relations
Phone: +41 61 688 8888 / e-mail: media.relations@roche.com

Dr. Nicolas Dunant Phone: +41 61 687 05 17	Sileia Urech Phone: +41 79 935 81 48
Dr. Barbara von Schnurbein Phone: +41 61 687 89 67	Karsten Kleine Phone: +41 61 682 28 31
Nina Mählitz Phone: +41 79 327 54 74	Nathalie Meetz Phone: +41 61 687 43 05

Roche Investor Relations

Dr. Karl Mahler Phone: +41 61 68-78503 e-mail: karl.mahler@roche.com	Dr. Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.com
Dr. Sabine Borngräber Phone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.com	Dr. Gerard Tobin Phone: +41 61 68-72942 e-mail: gerard.tobin@roche.com
Dr. Birgit Masjost Phone: +41 61 68-84814 e-mail: birgit.masjost@roche.com

Investor Relations North America

Loren Kalm
Phone: +1 650 225 3217
e-mail: kalm.loren@gene.com

 

Attachment

• 14122021_MR_POLARIX_en

FAQ

What are the results of the POLARIX study related to RHHBY?

The POLARIX study demonstrated that Polivy plus R-CHP improves progression-free survival by 27% compared to R-CHOP in untreated DLBCL patients.

When were the POLARIX study results presented?

The results were presented on December 14, 2021, at the ASH Annual Meeting.

What is the significance of Polivy for DLBCL patients and RHHBY?

Polivy represents a major treatment advancement for DLBCL, potentially changing the prognosis for many patients.

What is the current status of Polivy's approval for DLBCL?

Roche is working with global health authorities to expedite the availability of Polivy as a treatment option for DLBCL.