Over the past decade, pharmaceutical companies have begun to modify the way they do business to better respond to huge changes in the healthcare environment. These range from the transformation of once-fatal killers into chronic diseases to increases in diseases of affluence in emerging markets to an explosion of knowledge on the mechanisms of disease.
Today more people are living with diseases that would once have killed them and require drugs and medical care over an extended period. Twenty years ago the survival rate for heart disease during the first 30 days, for example, was about 10 percent, whereas today it is 60 percent, explains Paul Chew, senior vice president, chief science officer, and chief medical officer at Sanofi-Aventis, U.S., in Bridgewater. He adds that management of diabetes and cancer has improved significantly, making the diseases more chronic than immediately fatal.
Another significant trend is the huge growth in emerging markets like Brazil, Russia, India, China, Latin America, and the Middle East. “They are growing substantially in terms of affluence and the diseases of affluence, like heart disease and diabetes,” says Chew. India has a greater incidence of diabetes than any other country, he says, and China and Japan have seen significant growth in heart disease and stroke.
And of course the science behind the search for new drugs has advanced enormously. “Symptoms of disease are what is most superficial,” says Chew. “Underneath the range of symptoms are hundreds of potential mechanisms and diseases.” Breast cancer, for example, has dozens of types, depending on the types of cells and biomarkers, and the effectiveness of therapies depends on scientific understanding of these. With increased knowledge has come the development of more targeted therapies, says Chew.
Chew will speak on “BioPartnering with Sanofi-Aventis” at the BioPartnering Conference on Monday and Tuesday, June 14 and 15, at the Westin Princeton at Forrestal Village. Other speakers are Barbara Yanni, vice president and chief licensing officer for Merck and Company; Edward Saltzman, president of Defined Health; Adam Keeney, vice president of business development at Johnson & Johnson; and Cynthia Green, director of worldwide business development for Pfizer.
There will also be a panel discussion on “The Changing Landscape of the Biotech/Pharma Deal,” moderated by Saltzman, with panelists Pamela R. Demain, executive director of corporate licensing at Merck (see related story page 34), Christine T. Fischette, president of Enzo Therapeutics, and Mark J. Simon, president of the Williver Group.
Using special scheduling software, all registered life science companies will be able to set up 15-minute slots for making company presentations, on a first-come, first-served basis. Cost: $750 for BioNJ members; $850 for nonmembers. To register, go to www.biotechnj.org/biopartnering2010/. For more information, check the website, E-mail BioPartnering@BioNJ.org, or call 609-890-3185.
Sanofi-Aventis, developer of such blockbuster drugs as Plavix and Lantus, is based in France and is one of the world’s top pharma R&D firms. Worldwide, the company employs 100,000; in the U.S., about 15,000. In 2009 the company reported about $42 billion in sales and $5 billion in R&D investment, mostly in the areas of cardiovascular, oncology, and central nervous system medicines. Its U.S. headquarters, which Chew oversees, is based in Bridgewater.
Today much of the innovative scientific work in the search for new drugs lies outside of the research and development departments of large pharmaceutical companies. “What we know now is that many of the good ideas are in academic institutions and small biotechs — a small number of people with great ideas who need help in reaching the next stage,” says Chew.
In a statement on the Sanofi-Aventis website, www.sanofi-aventis.us, CEO Chris Viehbacher details the company’s interest in reaching out to others. “As an organization, we are fully committed to unleashing all the creativity and innovation we have within,” he states. “To do so, we intend to actively engage the world outside our walls.
“We sincerely believe that in tomorrow’s world, research will be all about networking and openness to scientific knowledge from several different sources: universities, biotech companies, research centers, and specialty pharmaceutical companies.”
While large pharma is on the lookout for good ideas, smaller biotechs and academic institutions are looking for ways to cover the costs and investments necessary to achieve regulatory approval and commercialize globally. “Biotechs and academe are reaching out at a time when the pharma industry needs to broaden innovation and transform the structure of how we do R&D and how we access new products,” says Chew, who estimates that approximately 55 percent of Sanofi-Aventis’s development portfolio is from external research and development partnerships or acquisitions.
Sanofi-Aventis recently restructured its research and development operations to take better advantage of innovative ideas outside its walls. Before this, Sanofi-Aventis had been a typical large pharma. “Sanofi-Aventis has been a very large traditional R&D organization, with most of the products, projects, and ideas coming from the inside,” Chew says. “It was an R&D factory.” But that approach had a significant downside. “If one part slows or breaks down, the whole assembly line comes to a halt,” says Chew.
In February, Sanofi-Aventis restructured its research and development operation into smaller units, each focusing on one of six therapeutic areas: oncology, diabetes, infectious diseases, fibrosis and wound repair, immuno-inflamation, and aging. Each is a small, entrepreneurial unit within the large company that will progress efficiently, says Chew. Within each group, the preclinical and clinical steps will proceed in miniature.
The new research units are different not just in terms of size but because they are placing the patient, not the disease, at the center of their development efforts. “We have changed our mindset from pharma to healthcare,” says Chew. As an example, he describes the work of one group in the area of aging, where Merck is looking at opportunities for preserving hearing and vision. Rather than focus only on disease, the group will be looking at how frail or impaired aging can be delayed or prevented. “Nobody minds getting old as much as the impairment,” says Chew.
In April Sanofi-Aventis announced a global license agreement with CureDM Group Holdings, a biopharmaceutical company in Philadelphia that develops new therapies that prevent, ameliorate, or reverse diseases of the metabolism.
The terms of this partnership offer benefits for both sides. CureDM will receive an upfront payment, as well as development, regulatory, and commercial milestone payments that could reach $335 million as well as tiered royalties on worldwide product sales, while Sanofi-Aventis was granted an exclusive worldwide license to develop, manufacture, and commercialize Pancreate, which is supposed to induce the pancreas to make insulin-producing cells.
Another alliance, also related to diabetes, is with AgaMatrix, a small company in the Boston area that develops products designed to improve the quality of diabetes care. AgaMatrix and Sanofi-Aventis have agreed to co-develop solutions in diabetes management that incorporate AgaMatrix’s WaveSense technology. It is a device plugged into a cell via a needle stick that gives very accurate blood glucose readings, allowing patients to adjust their insulin doses; it also transmits the reading to the patient’s medical record.
Sanofi-Aventis will commercialize the device through its global diabetes division along with current Sanofi-Aventis insulins and delivery devices.
Referring to both Pancreate and the WaveSense device, Chew observes, “With both, we are looking to help the patient rather than the disease by itself.”
Sanofi-Aventis’s reorganization of its research and development is part of its strategy to achieve sustainable growth by focusing on five areas: vaccines, emerging countries, innovative products, diabetes treatments, and consumer healthcare products. To drive success in each of these platforms, the company is working to increase innovation in research and development, seize external growth opportunities, and adapt its group structure to meet future challenges.
To take advantage of growth opportunities in emerging markets, Sanofi-Aventis is planning to provide more over-the-counter and consumer products in different parts of the world. As part of this effort, Sanofi-Aventis acquired Chattem, the Chattanooga-based company that manufactures and markets Gold Bond, Icy Hot, ACT, Cortizone-10, Selsun Blue, and Unisom. At the same time Sanofi-Aventis is seeking to convert its once-a-day antihistamine, Allegra, to an over-the-counter product that would be part of its consumer healthcare products platform.
Sanofi-Aventis is also in discussions with Merck and Schering-Plough about Merial, an animal products company that produces Frontline. Products for both companion animals and domestic livestock are a growth area, says Chew.
This new emphasis on sustainable growth counters the boom and bust cycle of pharma innovation alone. “Pharma is very important, and it becomes an upside on what I would call a floor of sustainable growth,” says Chew. “We have a tremendous opportunity in pharma, but it is not predictable that we will have one big product after another. We need to supplement that innovation and risk, because you don’t win all the time.”
Chew offered some examples of products in Sanofi-Aventis’s current pharmaceutical pipeline. In March the company filed Cabazataxil for men with metastatic prostate cancer who have failed Taxatir therapy, but it has not yet been approved; it will, however, get accelerated review.
Another is Iniparib, or BSI201, a new approach for women with triple-negative breast cancer, who do not have the three markers necessary to benefit from targeted therapies; 15 to 29 percent of these women present with metastatic, late-stage tumor, and a high mortality at one year. At phase 2, it showed an overall survival benefit with chemotherapy of about four months, which is, says Chew, “precious time for the patients.”
BSI201 was developed through a partnership with Bipar to bring the product from phase 2 to phase 3 and registration through its lung and ovarian cancer program. Sanofi-Aventis acquired Bipar in April, 2009.
Chew grew up in Rockland, Massachusetts, which is between Plymouth and Boston. His father, he says, had many careers in business, and he raised bonsai trees on the side as a hobby. His mother was a hairdresser.
Chew got all his degrees from Johns Hopkins University, including an undergraduate degree in human biology, his medical training, and residencies in both internal medicine and cardiology. He joined Johns Hopkins Hospital, where he became an assistant professor of medicine, an attending physician in radiology, director of the pacemaker clinic, and a member of the interventional cardiology staff. His research interests included acute interventional cardiology, cardiac biomechanics, and statistical modeling of pericardial biomechanics.
Chew was medical director of clinical cardiovascular development at Bristol-Myers Squibb, starting in 1992. He served as vice president of U.S. medical affairs from 1999 to 2001, responsible for Plavix, Avapro, Glucophage, and Pravachol. From 2001 to 2004,he was vice president and global head of metabolism and diabetes at Aventis Pharmaceuticals.
Between 2007 and 2009 Chew was president of U.S. research and development and vice president and therapeutic department head of metabolism, diabetes, and thrombosis at Sanofi-Aventis, U.S., with responsibility for Lovenox, Lantus, and the therapeutic development portfolio.