Investor Update

Basel, 01 June 2015

Roche presents encouraging update on metastatic bladder cancer data for atezolizumab (MPDL3280A, anti-PDL1)

  • More than half (57%) of people  with the highest levels of PD-L1 expression in this phase 1a study were alive at 1 year
  • Complete responses (CRs) were observed in 20 percent of people
  • Results indicated PD-L1 (programmed death ligand-1) expression correlated with how well people with previously treated, metastatic bladder cancer did on atezolizumab

Roche (SIX: RO, ROG; OTCQX: RHHBY) will today present updated data from a Phase Ia study in people with previously treated, metastatic urothelial bladder cancer (mUBC).  The study showed the investigational cancer immunotherapy atezolizumab (MPDL3280A) shrank tumours (objective response rate; ORR) in 50% of people whose mUBC expressed high levels (IC2/3) of PD-L1 (programmed death ligand-1). 57% of people in the study with high levels of PD-L1 expression were alive at 1 year. Atezolizumab continued to be well tolerated. The data will be presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).1

“Metastatic bladder cancer is a disease that has had no major advances in nearly 30 years, and we are encouraged that more than half of the people with high levels of PD-L1 expression were alive one year after their treatment started.” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development.  “In addition to this phase 1 study we look forward to sharing results from our phase II urothelial bladder cancer study, IMvigor210, later this year.”

The updated results from this phase Ia open-label study showed the investigational cancer immunotherapy atezolizumab (also known as MPDL3280A; anti-PDL1) shrank tumours in all PD-L1 subgroups.  In this study higher levels of PD-L1 expression (IC2/3) were associated with higher ORRs; levels of PD-L1 (programmed death ligand-1) were assessed by a test being developed by Roche, utilising the SP142 immunohistochemistry (IHC) antibody.

In the overall mUBC population:

  • Complete responses (CRs) were observed in 20% (9/46) of people with high levels of PD-L1 expression
  • Responders also included people with visceral metastases at baseline: 38% of people (32) with high levels of PD-L1 expression (IC2/3)  and visceral metastases experienced an ORR
  • 14% of people (36) with visceral metastases whose tumours expressed low levels of PD-L1 (IC1/0) experienced an ORR
  • 20 of 30 people had ongoing responses at the time of data cutoff
  • The median duration of response was not reached for the efficacy evaluable people (87/92) in the study,
  • ORR in people whose tumours expressed the lowest levels of PD-L1 (IC0/1) was 17 percent (7/41)

In May 2014, U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) for atezolizumab in metastatic bladder cancer for the treatment of people with PD-L1-positive mUBC after progression on or intolerance to a platinum-containing chemotherapy regimen.

Phase II and III studies in UBC are ongoing in late-stage disease (IMvigor210, GO29293; IMvigor211, GO29294) and planned in the adjuvant setting (IMvigor010, WO29636). Phase II data in 2nd Line UBC from IMvigor210 is expected later in 2015.

About the Phase Ia study of atezolizumab in metastatic UBC

  • Patients with previously treated, metastatic UBC were enrolled in an expansion cohort and received 15 mg/kg or 1200 mg IV atezolizumab q3w.
  • Efficacy-evaluable patients had a minimum of 12 weeks of follow-up (dosed by Jul 9, 2014; Dec 2, 2014 cutoff); median follow up was 14 months for the IC2/3 population and 12 months for the IC0/1 population.
  • ORR was assessed by RECIST v1.1 (unconfirmed), and archival biopsies were centrally evaluated for PD-L1 tumour-infiltrating immune cell expression by IHC.
Efficacy (n=87 efficacy-evaluable patients)*
PD-L1 ExpressionIC 2/3 (n=46)IC 0/1 (n=41)
ORR
N=87
50%
(95% CI: 35–65%)
9 (20%) CRs, 14 (30%)PRs
17%
(95% CI: 7–32%)
7 (17%) PRs
Median duration of responseNot yet reachedNot yet reached
Median PFS6 months (0+ to 18)1 month (0+ to 14+)
Median overall survival
N = 92
Not yet reached
(1 to 20+ mo)
8 months
(1 to 15+ mo)
1 year overall survival
N = 87
57% (41-73)
CI: 95%
38% (19-56)
CI: 95%

* 1 patient had unknown IHC status
CI: confidence interval; CR, complete response; IHC: immunohistochemistry; PFS: progression-free survival; PR, partial response; ORR, overall response rate; OS: overall survival.

Safety data (n=92)

  • Atezolizumab was well tolerated with no treatment related deaths
  • 8% of patients experienced a Grade 3-4 treatment-related adverse event (AE)
  • 1 patient  was discontinued due to a treatment-related AE
  • Renal toxicity has not been observed in atezolizumab treated patients to date
  • There were no grade 5 treatment-related AEs
  • Median safety follow up was 16 weeks

About atezolizumab

Atezolizumab (also known as MPDL3280A and anti-PDL1) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, Atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.

About metastatic urothelial bladder cancer

Metastatic urothelial bladder cancer is associated with a poor prognosis and limited treatment options. It is a disease that has seen no major advancements for nearly 30 years. Bladder cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012 and it results in approximately 145,000 deaths globally each year. Men are three times more likely to suffer from bladder cancer compared with women and it is also three times more common in developed countries than in less developed countries.

About Roche in cancer immunotherapy

For more than 30 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

About personalised cancer immunotherapy

The aim of personalised cancer immunotherapy (PCI) is to provide individual patients with treatment options that are tailored to their specific needs. Our PCI research and development programme comprises more than 20 investigational candidates, seven of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for our medicines. In the case of atezolizumab (also known as MPDL3280A), PCI begins with the PD-L1 (programmed death ligand-1) IHC assay based on the SP142 antibody developed by Roche. The goal of PD-L1 as a biomarker is to identify those people most likely to experience clinical benefit with atezolizumab as a single agent and which people may be appropriate candidates for combination therapies; the purpose is not to exclude patients from atezolizumab therapy, but rather to enable the design of combinations that will provide the greatest chance for transformative responses. The ability to combine atezolizumab with multiple chemotherapies may provide new treat.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-eight medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2014, the Roche Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs in R&D and posted sales of 47.5 billion Swiss francs. 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
1. Petrylak DP, et al. A phase Ia study of ATEZOLIZUMAB (anti-PDL1): updated response and survival data in urothelial bladder cancer (UBC), Abstract number: #8030 1 June 2015, 9:45 CDT, Chicago, United States