F. Hoffmann-La Roche Ltd: CHMP recommends EU approval of Roche's fixed-duration Columvi (glofitamab) for people with relapsed or refractory diffuse large B-cell lymphoma

• Once approved, Columvi will be the first CD20xCD3 T-cell-engaging bispecific antibody available to treat people in Europe with this aggressive lymphoma
• The recommendation is based on results from the phase I/II NP30179 study, where Columvi given as a fixed course induced early and long-lasting complete responses in people with heavily pre-treated or refractory diffuse large B-cell lymphoma¹
• Columvi is part of Roche's industry-leading CD20xCD3 T-cell-engaging bispecific development programme, which aims to transform the treatment experience for people with blood cancers using off-the-shelf and fixed-duration options
  
  

Basel, 26 April 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Columvi® (glofitamab), for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Columvi has the potential to change the current standard of care in DLBCL. As well as inducing early and long-lasting responses in people with heavily pre-treated or refractory DLBCL, potentially allowing patients a treatment free period, Columvi is designed to be given for a fixed period of time so that people know when their treatment will end. It is also an off-the-shelf therapy, meaning that people do not have to wait for cell collection and genetic engineering before starting treatment, which could be particularly important for patients who are at a high-risk of their disease progressing. A final decision is expected from the European Commission (EC) in the near future.

"New therapeutic options that are readily and broadly available are urgently needed for people with relapsing diffuse large B-cell lymphoma, which can become fatal without immediate treatment," said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development. "The CHMP's recommendation for Columvi brings us closer to providing a new, fixed-duration therapy for people with diffuse large B-cell lymphoma that induces early and long-lasting responses."

DLBCL is an aggressive (fast-growing) type of lymphoma and is one of the most prevalent types of blood cancer among adults.² Each year in Europe, an estimated 36,000 people are diagnosed with DLBCL.³ While many people with DLBCL are responsive to initial treatment, four out of ten are not cured with the current frontline standard of care, and the majority of those who require subsequent lines of therapy have poor outcomes.^4,5 Once approved, fixed-duration Columvi will be the first CD20xCD3 T-cell-engaging bispecific antibody available to treat people in Europe with this aggressive type of lymphoma following multiple prior lines of therapy.

The CHMP recommendation is based on positive results from a pivotal cohort in the phase I/II NP30179 study, where Columvi given as a fixed-course induced early and long-lasting responses in people with R/R DLBCL. Overall, 83.3% of patients were refractory to their most recent therapy, 90% were refractory to any previous line of therapy, and about one-third (35.2%) had received prior CAR T-cell therapy. Results showed that Columvi given as a fixed course induced a complete response (CR; a disappearance of all signs of cancer) in 35.2%
(n =38/108) of people and 50% (n=54/108) achieved an overall response (OR; the combination of CR and partial response, a decrease in the amount of cancer in their body). Among those who achieved a CR, 74.6% (95% CI: 59.19-89.93) continued to experience a response at 12 months, while the median duration of CR was not reached. The median follow-up for duration of response (DOR) was 12.8 months. Median time to first CR was 42 days (95% CI: 41-47). The most common adverse events (AEs) were cytokine release syndrome (CRS; 64.3%), neutropenia (a reduction in white blood cells [37.7%]), anaemia (30.5%) and thrombocytopenia (low blood platelet count [24.7%]). CRS was generally low grade (Grade 1: 48.1%; Grade 2: 12.3%). One patient discontinued treatment due to CRS.¹

Additional data from a larger cohort in the NP30179 study, published in the New England Journal of Medicine, reinforce the durability of Columvi. Fixed-duration Columvi resulted in early and long-lasting responses in people with heavily pre-treated or refractory DLBCL, with 39.4% of patients (n=61/155) achieving a CR and a median DOR of 18.4 months. Median time to first CR was 42 days (95% CI: 42-44), with the majority of responses reported at the first scheduled response assessment (approximately 1.4 months after the start of treatment). Half of patients (51.6%; n=80/155) achieved an OR. The most common AE was CRS, which was generally low grade (Grade 1: 47.4%; Grade 2: 11.7%) and occurred at initial doses. Columvi-related AEs leading to treatment discontinuation occurred in 3.2% of patients.⁶

Columvi was recently approved by Health Canada for the treatment of adult patients with R/R DLBCL not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma, who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR T-cell therapy or have previously received CAR T-cell therapy. Additionally, the U.S. Food and Drug Administration (FDA) accepted Genentech's Biologics License Application and granted priority review for glofitamab for the treatment of people with R/R large B-cell lymphoma. The U.S. FDA is expected to make a decision on approval by 1 July 2023. Submissions to additional health authorities worldwide are ongoing.

Columvi is part of Roche's broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development programme. Roche's portfolio also includes Lunsumio® (mosunetuzumab), which was granted accelerated approval by the U.S. FDA in December 2022 and conditional marketing authorisation by the EC in June 2022 for the treatment of adult patients with R/R follicular lymphoma after two or more lines of systemic therapy.

In an effort to help more patients in need of new treatment options, Roche continues to expand Columvi's clinical development programme, which includes the phase III STARGLO trial, evaluating Columvi in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in people with second-line plus DLBCL who are ineligible for autologous stem cell transplant. Additional phase III studies are also planned, including in first-line DLBCL.

About Columvi®] is a phase I/II, multicentre, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of Columvi® (glofitamab) in people with relapsed or refractory diffuse large B-cell lymphoma. Outcome measures include complete response rate by an independent review committee (primary endpoint), overall response rate, duration of response, progression-free survival, safety, and tolerability (secondary endpoints).

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. 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 Each year in Europe, it is estimated that 36,000 people are diagnosed with DLBCL.³

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), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes a T-cell-engaging bispecific antibody 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.

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

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

References
[1] Roche data on file.
[2] Cancer.Net. Lymphoma - Non-Hodgkin: Subtypes. [Internet; cited April 2023]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes.
[3] Calculation for Worldwide incidence: World Health Organization. GLOBOCAN 2020, Cancer Incidence and Mortality: IARC CancerBase No. 11 [Internet; cited April 2023]. 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=1collapse-group-1-4-0.
[4] Maurer MJ 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.
[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] Dickinson MJ et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. The New England Journal of Medicine. 2022. doi: 10.1056/NEJMoa2206913.

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