A Pharma Carol

In addition to his role in Global Research, Jonathan Knowles, Ph.D., is a member of Roche’s Executive Committee, board member of Genentech and board member of Chugai Pharmaceuticals. Since June 2004, he is also Chairman of the Research Directors’ Group of EFPIA (European Federation of Pharmaceutical Industry Associations).

NGP’s Jonathon Edgley asked him how pharma has transformed – and what has transformed it.

Q. How has the pharma R&D market changed in recent times?
A. We have access to new technologies and tools that have given us the chance to change the process of drug discovery tremendously. We are able to identify more quickly whether or not a compound will be a potential drug candidate. We are also able to understand the mechanism of action within the organism much better. This enables us to find applications of one drug in different disease areas e.g. oncology and rheumatoid arthritis.

Q. What have been the major catalysts for this?
A. Pharmacogenomics is a critical component. It enhances understanding of molecular pathology (i.e. the fundamental cellular derangements leading to disease). These are pivotal to devising new disease-fighting targeted strategies.

First examples for this development in the market are Herceptin and the AmpliChip CYP 450 test. Further developments are ongoing (AmpliChip P53, AmpliChip Leukemia).

Our aim is to offer clinically differentiated medicine and personalised healthcare; biomarkers and translational medicine are essential factors of this strategy.

Q. Do you agree with the premise that drug pipelines have been drying up?
A. As science has advanced, the discovery and development has become more complex, and this had led to higher costs of R&D. But if you look at our pipeline both from the perspective of quantity and quality I am very pleased with the potential new medicines we are creating. As a research-based company with partners and alliances globally, we create innovative products and we are confident we are pursuing the right strategy to ensure this will continue.

Q. With this in mind, is using the number of patent-protected NME launches currently an effective way to assess the success of R&D investment?
A. To assess productivity by numbers of NMEs is only one measure. Our strategy to understand how the drug works in detail has resulted in leveraging its value by identifying synergies in different disease areas. Most important is the clinical benefit brought to each patient. By finding numerous additional indications for one drug we are increasing the number of patients who will benefit from our understanding of disease and science.

Q. What are the time-to-market figures of an average product?
A. It really depends on the disease you are looking at. A product like an antibiotic or an anti-viral drug can be developed much faster than a drug in oncology or Alzheimer’s. On average the total process will take about 12 years.

Q. How important is it for companies to review R&D business models?
A. It is very important for all pharma companies to review all aspects of R&D in particular. This is needed to ensure the criteria for decision making is appropriate at each stage, with science and medicine being the key drivers.

Q. Will outsourcing and consolidation have a greater role to play?
A. Outsourcing is usually about cost saving, whereas in R&D it is the talent of your people that counts most. Therefore, it cannot be considered to be a major value driver. There is no evidence that consolidation increases R&D productivity.

Q. Roche has one of the strongest pipelines in the pharmaceutical industry. To what do you attribute this success?
A. Our strategy continues to focus on science and medicine. Our R&D strategy centres have their own decision-making criteria and we believe this increases innovation.

Q. What new technologies are – in your own words – “leading the way to a new paradigm in patient care”?
A. Better patient care is driven through our increasing understanding of molecular disease and the way individuals respond to different therapies. A number of high throughput technologies are also supporting research and development of potential new medicines.

“Our R&D strategy centres have their own decision-making criteria and we believe this increases innovation.” Prof. Jonathan K.C. Knowles, member of the Roche Executive Committee and Head of Global Research

Roche – the highlights

• Roche scientists Leo Sternbach, Lowell Randall and Earl Reeder discover a class of psychotropic medicines called benzodiazepines, e.g. Librium and Valium. Librium was launched in 1960 and Valium in 1963.
• Research efforts that led to the invention of Polymerase Chain reaction (PCR) and the purification of Tag Polymerase.
• Discovery of mycophenolate mofetil (CellCept) a potent immunosuppressant.
• The development of pioneering blood glucose monitoring products and services (Accu-Check).
• Synthesis of Rimifon, which was credited with nearly eradicating tuberculosis.
• Development of the manufacturing process of Fuzeon.
• Development with Genentech of interferon alfa-2a (Roferon-A) Roche’s first genetically engineered therapeutic protein.
• Synthesis of anti-cytomegalovirus (CMV) compounds (Cytovene and Valcyte).
• Development of Amplicor HIV-1 and HCV Monitor test.
• Synthesis of naproxen, a nonsteroidal anti-inflammatory compound (Naprosyn, Aleve).

Roche worldwide
1962: Product introduction of Fluorouracil Roche, the company’s first anti-cancer drug, paving the way for future activities in the field of cancer chemotherapy.

1980: Pure interferon alpha protein is isolated by Roche scientists. Genentech and Roche start a joint project to produce interferon alpha in genetically engineered bacteria.

1982: Rocephin, an antibiotic of the cephalosporin class, is launched in Switzerland only four years after its discovery.

1984: Niels Kaj Jerne, the first Director of the Basel Institute for Immunology, is awarded the Nobel Prize for medicine for his seminal work in immunology. Sharing the award with him are César Milstein and Georges Köhler for their discovery of monoclonal antibodies.

1985: World premiere of Reflotron the highly innovative device for use in doctors’ offices. In the same year, the company is awarded German industry’s Innovation Prize for Reflotron.

1986: First genetically engineered product, Roferon-A (interferon alpha-2a), on the market.

1991: Roche acquires the worldwide marketing rights to the polymerase chain reaction (PCR) technique from Cetus Corporation and develops it for industrial use. Capable of detecting even minute amounts of genetic material, this technique opens the way to developing diagnostic tests that are fast, sensitive and specific.

1992: The Diagnostics Division launches the first PCR-based diagnostic tests under the Amplicor trademark.

1995: Roche scientists discover a new class of therapeutics, protease inhibitors, for the treatment of AIDS.

1997: Humanised monoclonal antibodies MabThera (cancer therapy) and Zenapax (prevention of organ rejection after transplantation) are launched.

1999: Launch of Tamiflu, the first neuraminidase inhibitor in a pill form, designed to treat all common strains of influenza.

2001: Pegasys, a pegylated interferon, is introduced for the treatment of chronic hepatitis C as monotherapy as well as in combination with Copegus (anti-viral ribavirin).

2002: Roche and Chugai sign a broad-ranging collaboration agreement on small molecule drug research, closely collaborating to develop common technology platforms to facilitate the creation and advancement of research projects.

2003: Roche introduces the AmpliChip CYP450 – the world’s first pharmacogenomic microarray for clinical applications to identify naturally occurring variations in genes.

2003: Fuzeon is launched, representing a new class of HIV treatment – fusion inhibitors.

2004: Introduction of Avastin for first-line treatment of metastatic cancer of the colon or rectum. This innovative therapy works by preventing the formation of new blood vessels, a process called angiogenesis.