On average, only about five out of ten patients who receive a given therapy actually benefit from it, while some may experience side effects.

Thanks to advances in new research disciplines, scientists now have a better understanding of disease at the molecular level. As a result, they are able to distinguish patient subgroups in which different causes drive what has traditionally been regarded as a single disease. In oncology, this has led to efforts to identify genetic characteristics affecting patients’ responses to particular therapies.

Identifying clinically significant patient subgroups is a key element of our Personalised Healthcare strategy, which marries new diagnostic techniques with advances in biotechnology in an effort to develop more targeted, more efficient therapies.

This strategy is being systematically implemented at every stage of new product development at Roche and is aimed at helping us

• better understand disease diversity
• identify differences between patients
• identify the best drug targets
• improve the quality and efficiency of our R&D efforts
• develop biomarkers and diagnostic tests

Researchers across the globe are making enormous progress in understanding diseases and their root causes. This knowledge is leading to a dramatic increase in the identification of biological targets to fight many diseases. At Roche we combine our strong in-house research capacities and know-how with the latest external advances in science to identify potential drug candidates and biomarkers.

Pharmaceuticals and Diagnostics under one roof

For Roche the crucial edge comes from integrating the knowledge in our Pharmaceuticals and Diagnostics Divisions and drawing on it throughout the R&D process, from early research to approval of new diagnostic tests and medicines and their use by patients. The close cross-divisional cooperation between our R&D scientists distinguishes Roche from other companies.

Metastatic melanoma is the deadliest and most aggressive form of skin cancer. It develops when the pigment cells in the skin grow in an uncontrolled way. If identified and treated early, melanomas respond well to treatment. But once secondary tumours (metastases) have formed and spread through the body, the chances of recovery are slight.

Activation of specific receptors initiates an intracellular signaling cascade which ultimately leads to cell proliferation and survival. In metastatic melanoma, a specific protein is oncogenic in approximately 50% of cases resulting in overactive down-stream signaling and cell proliferation. Therefore, this oncogenic protein is a potential therapeutic target in metastatic melanoma.

A specific subgroup of mutations cause constitutive activation of this protein allowing it to signal independently of upstream cues.

The majority of these mutations are readily detectable via a validated and approved diagnostic test.

The constitutively active oncogenic protein then activates another protein, which then translocates into the nucleus. Here it binds to different transcription factors. This constitutive signaling by this oncogenic protein causes excessive trancription of genes that promote cell proliferation and survival in vivo, this leads to tumour genesis.

In summer 2011 the US health authorities simultaneously approved a new oral, highly selective small molecule inhibitor of this specific oncogenic protein and its companion test. In late 2011 the drug and test were made available in Switzerland.

This medicine is designed to target the active confirmation of this oncogenic protein, which in turn is expected to prevent activation of other proteins and thus inhibit down-stream signaling. This may inhibit cell proliferation and result in apoptosis, leading to tumour regression.

Screening patients for these mutations using a validated companion diagnostic will help to identify those patients that may benefit from this treatment option.

This is the first and only FDA-approved personalised medicine shown to improve survival in people with this specific mutation-positive metastatic melanoma and it shows the benefits of Roche’s Personalised Healthcare approach.

Infection with the hepatitis C virus (HCV) can cause acute or chronic liver damage and ultimately lead to liver failure, cirrhosis or cancer of the liver. Worldwide, about 170 million people are infected with HCV.

In 2001 Roche received the first approval of its combination treatment for people with hepatitis C infections which became the standard treatment. This approval was for treatment duration of 48 weeks.

Today we know that there are a number of subtypes of HCV that differ not only in their molecular structure but also in their responsiveness to treatment. Roche has developed molecular tests that can identify which HCV subtype a patient has. This information helps physicians predict how long a patient should continue treatment (e.g. 24, 48 or 72 weeks) in order to achieve a lasting virological response.

Personalised Healthcare – improving physicians' ability to predict response and adjust treatment

Roche’s Personalised Healthcare strategy draws on advances in molecular biology to

• monitor patients' responses to therapy
• adjust the duration of therapy to patients’ needs
• administer medicines at precisely the right time within a long-term treatment strategy
• develop new diagnostic tests and medicines in a more focused, efficient way