Investor Update

Basel, 01 June 2014

Roche to present phase I data on investigational cancer immunotherapy anti-CSF-1R (RG7155) antibody in patients with Pigmented Villonodular Synovitis (PVNS)

  • Encouraging results from  Phase 1 study in a rare disease with high unmet medical need
  • FDA has granted orphan drug designation for RG7155 in the treatment of PVNS

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the company will present new data on its anti-CSF-1R monoclonal antibody, RG7155, at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2014. RG7155 is an investigational medicine designed to decrease tumor-associated macrophages, which are induced by cancers to suppress the body’s own anti-cancer immune response. PVNS is a rare, locally aggressive, neoplastic disease of the synovia of large joints. This disorder is mainly driven by accumulation of macrophages; thus, it has been considered as a model disease to prove RG7155 activity.

Today, encouraging results will be presented from a phase I dose escalation and extension study with RG7155, which induced objective responses according to RECIST in 83% (15/18) of evaluable patients with advanced PVNS. RG7155 was well tolerated with the majority of adverse events being grade 1 and 2. Data will also be published today in the online edition of the journal Cancer cell1.

“PVNS is a debilitating disease for many of the patients affected, representing a significant unmet medical need,” said John C. Reed, M.D. Ph.D., Head of Pharma Research & Early Development (pRED) at Roche. “These encouraging data from the Phase 1 study are an important step in establishing the ability of RG7155 to treat patients with macrophage-driven diseases where CSF-1R plays a role.”  

PVNS is a rare, locally aggressive, neoplastic disease of the synovia of large joints affecting people in the midst of their lives (mostly 20-50 years). The molecular pathology is characterized by an inflammation of the synovial lining cells in joints and tendons caused by the overexpression of colony-stimulating factor-1 (CSF-1)2. This leads to a massive recruitment of colony-stimulating factor-1 receptor (CSF-1R) expressing cells, e.g. macrophages, which form the bulk of the tumorous mass. Tumor-associated macrophages are thought to be responsible for resistance of solid tumors to immunomodulatory therapeutics such as antibodies targeting PD-1 and PD-L1.

RG7155 is a humanized monoclonal IgG1 antibody that specifically targets CSF-1R, blocking its activation by CSF-1. In the multicenter Phase I clinical trial, RG7155 therapy has been shown to reduce consistently and significantly CSF-1-dependent macrophages in the joints of PVNS patients and also in the tumors of cancer patients.  

RG7155 will be further explored as monotherapy as well as in combination with other therapies including other cancer immunotherapy agents.

About the Phase I RG7155 study

BP27772 is an open-label, multicenter, dose escalation Phase Ia/Ib study with extension phase to evaluate safety, pharmacokinetics and activity of RG7155, administered as an intravenous infusion as monotherapy and in combination with paclitaxel in patients with advanced solid tumors. 124 patients have been enrolled including 22 patients (DE and extension) with inoperable progressive or relapsing PVNS. To date clinical activity was evaluated in 17 respectively 18 patients using FDG-PET (at 4 weeks after treatment start; EORTC criteria) and MRI (at 6 weeks; RECIST 1.1). Pre- and on-treatment biopsies of tumor and surrogate skin tissue as well as peripheral blood PD markers were analyzed. RG7155 is further explored in monotherapy extension cohorts in mesothelioma, pancreatic, breast and ovarian cancer. In addition, a combination arm with weekly paclitaxel in metastatic breast cancer and ovarian cancer is ongoing.

About the Phase I RG7155 extension study in PVNS

The Phase I DE and extension study enrolled 22 patients with inoperable progressive or relapsing PVNS. Treatment with RG7155 resulted in rapid onset of functional and symptomatic improvement occurring in the vast majority of patients within the first 3 infusions given every 2 weeks. Tumor MRI assessment was performed at baseline and at 6 weeks on treatment with follow up assessments every 6 weeks.  15/18 patients assessed (83%) showed a time point partial response (MRI at 6 weeks according to RECIST version 1.1.). In addition, 15/17 patients assessed (88%) showed a partial metabolic response (FDG-PET at 4 weeks, EORTC criteria). Currently, all except one patient remain clinically progression free (longest follow up 22 months). Patients received doses from 900 mg onwards, escalating to 1350 mg and 2000 mg, respectively. The maximum tolerated dose (MTD) was not reached and the optimal biological dose (OBD) for the extension cohort (1000 mg) was defined based on PD biomarker read-outs.

Overall, RG7155 was well tolerated with mostly only grade 1 and 2 adverse events (AE). Out of 22 patients already available for the safety analysis, most common AE were asthenia (68%), periorbital and peripheral edema (59% and 45%, respectively) and pruritus (45%).  Four patients experienced a serious adverse event  (periorbital edema, appendicitis, Lupus erythematosis and erythema) at doses higher than the OBD.

About RG7155

RG7155 is an investigational monoclonal IgG1 antibody designed to target and deplete tumor-associated macrophages (TAMs) in the tumor tissue. TAMs are an abundant component of the tumor microenvironment of many tumor types supporting tumorigenesis by suppressing the local immune system and promoting growth of tumor cells.  RG7155 specifically targets TAMs by binding to colony-stimulating factor-1 receptor (CSF-1R) on the cell surface and blocking its activation by CSF-1. RG7155 therapy has been shown to significantly reduce CSF-1 dependent macrophages in PVNS and in tumors of cancer patients.

About PVNS

Pigmented Villonodular Synovitis is a rare disease characterized by proliferation of synovial tissue in the joint and tendon sheath. The neoplastic process is driven by a specific genetic translocation leading to the overexpression of CSF-12 and a massive recruitment of CSF-1R-expressing macrophages that form the bulk tumorous mass. Even though the disease rarely metastasizes, it is locally aggressive and disabling. Patients are usually diagnosed at an age between 20 and 50 with equal sex distribution. Standard therapy is surgery but relapse rates are high. Patient’s quality of life is often impacted by tumor-related symptoms and surgical sequelae. There is no approved drug treatment available for PVNS3.

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-four medicines developed by Roche are included in the World Health Organisation Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2013 the Roche Group employed over 85,000 people worldwide, invested 8.7 billion Swiss francs in R&D and posted sales of 46.8 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.Ries et al., Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell, in press
2.Ottavini et al., Pigmented Villonodular Synovitis: a retrospective single-center study of 122 cases and review of the literature. Semin Arthritis Rheum 2011: 40, 539-546.
3.West et al., A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. PNAS 2006: 103, 690-695.