"The worst thing in the world that any of us could do would be for one part of our CME enterprise 

to interfere with either the professional or legal obligations of other parts of the enterprise," Murray Kopelow, chief executive of the Accreditation Council for Continuing Medical Education (ACCME), said in his opening remarks as he addressed an initially antagonistic—if not hostile—crowd on the second day of 

's Second Annual Med Ed Forum last month in Philadelphia. Facing an audience of more than 150 medical education providers and pharma company executives waiting for his session, Kopelow did an admirable job of assuaging the audience's distress over an ACCME staff-written Q&A (released a few weeks before the conference) that attempted to clarify stipulations of the organization's newly updated "Standards for Commercial Support (SCS)." At the end of his presentation, even the most belligerent attitudes seemed tamed. The following comments have been excerpted from Kopelow's comments during his formal presentation and the subsequent questions.  

Robert W. Doyle, vice-president of marketing operations			

The ACCME board of directors charged the staff with the responsibility, and gave us the authority, to interpret and explain its positions in the context of what we knew from the process of developing the SCS. The resource materials were created, I promise you, as educational resources to help bracket the landscape—not as instructions to say, 'Do this and you're going to be OK, and if you don't do these four things you are going to be out of compliance.' 

I've tried over the last 10 years not to give specific examples of what a provider should do because the facts and circumstances for each provider are unique. We were asked at this time to take a different role.  Resolving conflict of interest is something that we've never asked CME providers to do before. In the educational resources we tried to give examples of what providers could do. 

Novartis; Mary L. Lacquaniti, CAE, executive director, Healthcare Marketing and Communications Council, with Susan Torroella, CEO of Columbia MedCom Group			

But providers need to understand that those are just educational resources. If they stay on our website or if they disappear, if they get edited or changed, it doesn't mean we are changing policy, and it doesn't mean we are changing accreditation criteria. The decision-making criteria will be established over the next few years, as providers come forward with their approaches to compliance.  

We are telling providers that context matters. The context in which they operate—who their audience is, what their educational objective is, what their facts and circumstances are—will dictate their strategy. It's up to the provider to pick strategies to address these issues. It's up to the provider to decide what can be done to ensure that commercial bias is not inserted." 

 John Kamp, PhD, partner, Wiley Rein & Fielding 			

The standards are a key part of ACCME's overall strategy to ensure the credibility and validity of CME. Credibility and validity are, to a great extent, determined by who is in front of the audience teaching. It is important that the best and the brightest are teaching and that CME is independent of commercial interests. Transparency through disclosures is a large part of the credibility of CME.  

Most important, of course, is that in order for CME to serve the public's interest, what is taught needs to be true. There is promotional education that is valid and has face validity. But what distinguishes continuing medical education from promotional education is that CME is by and for the profession. The content has been created independently from any commercial interest. 

Tom LarraÃÂ±aga, group publisher of Pharmaceutical Executive magazine, with Steven Mankofsky, strategic account director, Advanstar Medical Economics, and Jerry Silverman, RPh, president of Bimark Medical Communications;			

I am not saying that education dependent on commercial interest is wrong, or invalid, or not true. It is just education created by commercial interests and not by the CME system."  

The content or format of a CME activity or its materials must promote improvements or quality in healthcare. That is the most important goal of CME, and we need to focus on that because that is what ACCME's member organizations, the public, and the learners expect." 

	Andy Bender, principal of Polaris Management Partners			

 One of the big new issues with these updated standards is resolution of personal conflicts of interest. Here, the most important things to the ACCME are the word 'mechanism' and that providers are engaged in the process of managing, or resolving, conflicts of interest. This has two major components—the identification and the resolution. Resolving conflict of interest means taking steps to ensure that the content of the activity is aligned with the interest of the public. When a relevant financial relationship exists and the content is relevant to that commercial interest, providers must insert safeguards against bias. Providers can, for example, address conflict of interest through managing a person's role or assignment in CME, or through external validation of content. We are moving away from just disclosure of relationships and raising the bar. A disclaimer saying, 'I know this is a biased presentation because I firmly believe it,' is not a standard that we use for managing conflicts of interest. External validation can be accomplished by reference to the scientific literature. There are evidence-based reviews and meta-analyses and syntheses for almost everything that we do as physicians. We need to recognize that quoting the literature, citing four articles that support what is being said, is very different from referencing a meta-analysis or meta-synthesis as the best available evidence. This expectation has been articulated in ACCME's 2002 Content Validation statements. 

Eric D. Peterson, MEd, president of the National Alliance of Medical Education and Communications Companies (NAMECC), and vice-president and general manager of Bimark Center for Medical Education.			

Another example of external validation is the circumstance where the educational space contains the world's experts. When someone brings new information from his or her own research or offers personal thoughts of what should be done, it is effectively being subjected to a peer-review process because the room contains peers who can judge what they are being asked to learn. They can say, 'this is biased,' 'this is only because of your commercial interest,' or 'the data don't support that conclusion.' That process, that mechanism, resolves conflicts of interest. There are safeguards in place. This is the way professionals and clinical scientists interact, at the expert level." 

 The 1992 SCS said a commercial interest could distribute enduring materials, and the provider was responsible for their use as a CME activity. In element 4.5 of the 2004 Updated SCS, ACCME says providers must not use commercial supporters as a distribution vehicle for a CME activity. The goal of this [SCS] element is to separate detailing from the physician's participation in CME. 'Let's sit down and do this activity together while we are detailing the product,' fails to separate education from promotion. But it's not up to ACCME to say what commercial supporters can buy or do. ACCME does not regulate commercial supporters; they are accountable to other organizations or institutions."  

 Implementing the Updated SCS is a process of change. After May 2005, as providers start new activities, we expect that they will implement the new elements of the Updated SCS. I need to emphasize that there are a limited number of new elements in the 2004 document. We understand that it will take some time, energy, and resources to implement something new, and we expect that providers will have the time to make this transition."  

The range of strategies and tactics that providers will adopt is yet to be seen; most mechanisms have not yet been described. ACCME has offered some clarification and examples, but ultimately the providers will decide how they will practice. Providers know that ACCME operates under an improvement model. When they are out of compliance, it is their responsibility to come into compliance within a designated period, usually a year. We require that providers demonstrate this  improvement in an ACCME Progress Report, a  description of current practice accompanied by documentation that verifies compliance. In our experience, 90 percent of providers who are not in compliance can and do demonstrate compliance by the end of one year. Virtually every time, the remaining 10 percent are in compliance after another six months. We know that this improvement model works. We rarely have to take away accreditation, but we do it on occasion."  

The ACCME considers itself a voluntary, self-regulated system—not a regulatory body. We fundamentally do not believe that enforcement is the major cause of compliance. We believe that we are an organization that articulates the standards that reflect the values of the profession to people who understand the values of the profession. In that context, no enforcement or regulation is required. We do not need to force providers into compliance. When people share your values and they know exactly what the requirements mean, they will implement them. That is the case with the vast majority of accredited providers within the ACCME system."

Special thanks to AndrÃ©a Azpeitia, conference producer, for her help with this article.

Articles

Features

"The worst thing in the world that any of us could do would be for one part of our CME enterprise to interfere with either the professional or legal obligations of other parts of the enterprise," Murray Kopelow, chief executive of the Accreditation Council for Continuing Medical Education (ACCME), said in his opening remarks as he addressed an initially antagonistic-if not hostile-crowd on the second day of Pharmaceutical Executive's Second Annual Med Ed Forum last month in Philadelphia.

Conflict Resolution

Chairman of the Harris Poll, Harris Interactive

I have an IQ test for forecasters. If they are brilliant like the late Herman Kahn, they never make forecasts that can be proved wrong in their lifetime. If, like me, you conduct political polls, you make a forecast on Election Day morning that may be proved wrong that evening. That obviously indicates a very low IQ. So I am happy to raise my IQ level by offering 20 forecasts regarding the next few years:

President Bush will make good on some of his campaign promises for making healthcare more accessible and affordable, but they will not substantially reduce the number of people without insurance. 

The number of uninsured and underinsured will continue to increase. 

Congress will start work on ways to "fix" or "improve" the Medicare Modernization Act-especially its pharmaceutical benefit plan. 

Washington will do little to reduce the rapidly increasing long-term costs of Medicare. 

Medicare Advantage plans will increase their share of Medicare beneficiaries, but most beneficiaries will remain in traditional fee-for-service Medicare. 

				The ideological debate about roles of government and "the market" will continue. On the left: the proponents of universal coverage, single-payer systems, and healthcare as an entitlement. On the right: proponents of competition, choice, personal responsibility, and market forces. Bismarck, Beveridge, and FDR vs. Adam Smith and Milton Friedman. Neither side will land a knockout punch, but advocates of market forces will win some battles. 

There will be better metrics to evaluate the quality of care provided by hospitals, physicians, and health plans, but they will not be good enough to persuade those being evaluated that they are fair. 

The "pay for performance" movement will grow, led by third-party payers (e.g., Leapfrog and Bridges to Excellence), the Institute of Medicine, academics, and policy wonks. Many doctors and hospitals will complain. 

Pressure will grow to create a new federal government agency to evaluate the cost-effectiveness of diagnostics, drugs, procedures, and other treatments, influenced by those in the United Kingdom, Australia, Germany, and other countries. 

High deductible and "consumer-driven" health plans will grow rapidly-but from a small base-and will be described as "consumer empowerment" or "consumer choice" plans. 

Out-of-pocket costs will rise even faster than total healthcare spending. This trend will be described as increased "personal responsibility." As a consequence, nonadherence/compliance will increase substantially. 

The IT revolution will move forward (slower in the United States than abroad), but it will be too soon to know if it can deliver on its promise of improved quality, fewer medical errors, increased efficiency, and lower costs. 

The insured public will respond positively to "choice" and negatively to higher out-of-pocket costs. 

Healthcare costs will continue to grow much faster than the GDP (but more slowly than in the early 2000s). The main drivers: new technology, increased utilization, and hospital price inflation. 

The "Vioxx effect" will cause more drug companies to fund clinical trials of approved drugs, following the example of Pfizer's new trial of Celebrex. 

All major drug companies will list clinical trials of their new drugs in a register, whether this is mandatory or voluntary, and release the results, both positive and negative. 

A drug importation (or "reimportation") bill will pass and be signed into law, but it will fall short of what many advocates are asking for. 

If a drug importation bill-or the threat of one-does not reduce the price differential between US, Canadian, and European drug prices, Congress will look for other ways to do so. 

Drug companies will start to take a tougher line with some foreign governments on drug pricing, including walking away from some countries. 

 Industry's pricing in the United States will be less aggressive as companies seek to diminish demonization.

 Companies' pricing strategies will become less aggressive.

	Â» Midsize players with targeted therapeutics may begin to merge and threaten the dominance of some big pharmas, which are struggling to prove that blockbusters are safe and are paying large sums to those who think otherwise. 

Management consultant and health economist

In 2005, the driving forces shaping the outlook for inrormation technology in the pharmaceutical marketplace include the demand for monitoring and measuring healthcare quality and patient outcomes; growing concern about a safer pharma supply chain; and the global demand for transparency. Together, these drivers converge toward the following events: 

 Health plans-both private and public-are arming physicians with PDAs and personal computers to enable e-prescribing (eRx). CafÃ©Rx, an alliance of Allscripts, Cisco, HP, Microsoft, NCPDP, NDCHealth, and others, will provide end-to-end eRx capability. This initiative could be eRx's tipping point. Health plans and payers will benefit as physicians have formulary information, including available generic substitutes, for each patient at the point of prescribing. 

 Payers and providers are increasingly able to marry patient data from different sources. As claims data can be integrated with patient outcomes data (for example, employer's return-to-work statistics with patients' perceived quality of life), payers and plans will be able to compare the true cost-effectiveness of various treatments. Groups such as the National Business Coalition on Health have begun to study this process. 

 Importation of pharmaceuticals in the United States has gained bipartisan support in Congress. To ensure a safe supply chain, pharmaceutical manufacturers, distributors, and retail pharmacies will come together to adopt the first stages of RFID across the supply chain. 

 The call for greater transparency of clinical trials influential peer-reviewed medical journals will usher in a new phase of online clinical information that can be used by patients, clinicians, and others interested in delving into greater details learned in trials. The level of details published online has yet to be negotiated, which will happen in a careful dance involving publishers, researchers, and their respective lawyers. 

Public and private  health plans will offer end-to-end electronic prescribing.

Â» Cost consciousness will rise again and again-not only among consumers. Pharma will tighten its belt to compensate for the  squeeze on profits. 

Editor-in-Chief, Applied Clinical Trials magazine

While profits in the pharmaceutical industry have slowed over the past few years, the clinical trials outsourcing market has grown by leaps and bounds. The industry has witnessed some unexpected divergences and paradigm shifts over the last year. This is reflected in sponsors now rethinking how partnerships and alliances with CROs, laboratories, IT firms, public and private research organizations, and academia can fit together to maximize their resources. Future trends will include innovative  partnerships, the incredible evolution of diagnostic tools, amazing strides in pharmacogenomics, and specific disease treatments in the development and marketing of new drugs.

Clinical trials:  Outsourcing is still on the rise. Look for new approaches to partnerships.

Senior engagement director, Cambridge Pharma Consultancy

Over the past few years, the battle over US pharmaceutical prices has focused on importation. There is a widespread perception that importation is the primary threat to free pricing. But that perception is not supported by analysis of how importation is likely to play out over time, or by the European experience of parallel trade. Nor does it take into account other threats to US prices.       

			The largest of these threats is the Medicare drug benefit. Though language in the act bars the government from direct price negotiation, precedents from Medicare and other federal programs suggest that lawmakers will be pushed to reconsider these "noninterference" protections. If that happens, the real battle over US pricing in the medium term will emerge not from importation-but from Medicare.       

This is the time of year to not only reflect on the past, but to ponder the future.Forget soothsayers, prophets, and fortune tellers' crystal balls. Inside are predictions from some of industry's key thought leaders.

Forecast 2005

Analysts and consultants dip into the pipeline to select 25 products that are going to make a difference for pharma—and patients.  			

Will this be the year drug importation staggers the industry? Will the sales force keep growing? What's next in technology? Our panel of prophets answer these questions and more. 

All those patients. All  those scientists. And all those US-trained entrepreneurs looking for partners. No wonder pharma is increasingly turning to China. 

New standards for pharma-supported medical education aren't as impossible as they seem. ACCME's Murray Kopelow explains why. 

	If ethics were just about telling wrong from right, it would be hard enough. The trickiest part, these experts say, is choosing between right and right. 

The managed-care backlash is easing 					

Malaria treatment Mosquirix halves infection rates in children 

 The European Court of Justice sympathizes with industry 

 FDA strengthens warnings on Mifepristone 

				Would you enroll your child in a clinical trial? 							

 How doctors assess  journal article quality. 

Mark Scheineson, a former FDA official, urges pharma companies to contest class-action suits aggressively. 

Bush's re-election was good news for pharma, but there are still some important issues for the next four years. 

In Britain, a new law lops another 7 percent off drug prices—by setting limits on profits. 

Some courts are rejecting "grouping" of lawsuits against pharma. Here's why that's good news. 

 is currently the seventh-largest healthcare market in the world. By 2010 it is expected to become the fifth-largest, with pharmaceutical sales of $24 billion, and some experts believe that by 2020 China will surpass the United States to become the world's largest pharmaceutical market. 

As China has become more affluent, there has been increasing demand for therapeutics, medical devices, and other healthcare products and services. Hepatitis B and C and HIV/ AIDS continue to be major problems, but the overall Chinese disease profile is looking more and more like that of the Western world. Cancers (especially lung, liver, colorectal, and gastric) and cerebrovascular, cardiovascular, and respiratory diseases accounted for 77 percent of deaths in 2000, and it is expected that changing lifestyles will soon put the spotlight on diabetes and obesity.  

Meanwhile, the expanding class of Chinese "luxury consumers" is expected to reach 100 million in the next decade. These affluent individuals have fueled the explosive entry of upscale brands such as Gucci, Armani, Cartier, and Mercedes into China and have been the force behind the rise of new private hospitals with US-style premium services. These consumers demand better healthcare, and they can afford it; they represent a lucrative market for foreign companies marketing state-of-the-art medical treatments. 

China offers tremendous opportunity for healthcare companies. Chinese companies are looking for global partners on many levels: to provide novel Western pharmaceutical, diagnostics, and medical device products that will be marketed in China by local partners; to feed the country's burgeoning drug discovery, contract research, and contract manufacturing industries; and, in the long run, to market Chinese-discovered and- developed products globally. This article will look at the market, the "returnee" entrepreneurs who are transforming the Chinese life sciences industries, and some of the most important opportunities for partnership—especially in the emerging market for traditional Chinese remedies. 

Opportunities in Life Science and Healthcare

Last year, General Motors made a profit of $437 million in China—more than half its entire North American profits, at close to eight times its North American margin. In the high-tech arena, the chip giant Intel generated revenues of $3.7 billion from China last year, making the country its third-largest market in the world and one of the most profitable. With venture investment of more than $200 million in 50 Chinese companies, Intel is possibly the most dominant high-tech brand in China. By comparison, pharmaceutical companies have lagged behind in their expansion into China. According to some estimates, for example, Pfizer's 2003 Chinese pharmaceutical revenue accounted for  less than 1 percent of total revenue (approximately $140 million out of $45 billion), although the company is reported to have invested more than $500 million in China since the 1980s. Pfizer currently markets more than 40 pharmaceuticals there and plans to launch 15 new drugs in China in the next five years.  			

In addition to Pfizer, the big pharmaceutical players in China include:  		

 GlaxoSmithKline, which has invested $400 million in the country and last year reportedly generated about $300 million in revenue there. 

 AstraZeneca, which has invested $140 million in China, achieved revenues of $151 million in the country last year, and expects to increase its Chinese sales force to 900 people. 

 Novartis, which expects to see 20 percent annual growth in its China business in the next five years and has invested $70 million in China since its entry in the late 1980s. Sales have been growing by an average of 20 percent annually since 2000 and last year hit $120 million.  

At least five multinational pharma companies have launched R&D operations in China or are considering such an initiative. In October, Roche announced the opening of Roche R&D (China) at the Shanghai Zhangjiang Hi-Tech Park, the company's first R&D facility in Asia and its fifth worldwide, and Eli Lilly established a research operation in the same park this year. AstraZeneca started its East Asia Clinical Trial Center in Shanghai in April 2003. Novo Nordisk China relocated its R&D center to the Beijing Zhongguancun Life Science Park and doubled its size this August. Russell Greig, president of international pharmaceuticals for GSK, said his company would consider establishing a R&D center in the country, if the government puts the correct regulatory regime in place, and Pfizer is close to making a decision about its China R&D center, according to Allan Gabor, Pfizer China's general manager. 

China has about 20,000 biologists with a master's degree or higher. They are paid one-fifth to one-third what similarly qualified biologists make in the United States. This vast, competitively priced talent pool is also being explored not just by Big Pharma, but also by biotech companies, such as Basilea Pharmaceutica, a Swiss-based, Roche spin-off that develops small-molecule anti-infectives. In May 2002, Basilea set up JIPharma, an impressive R&D center in Haimen, Jiangsu province, near Shanghai. With a staff of nearly 100 people, mostly chemists, recruited from leading Chinese faculties, JIPharma works to full international standards on Basilea R&D projects.  

Anthony Man, Basilea's CEO, cautions that the war for talent could be highly competitive, particularly in big cities. This will drive labor cost up in a short time, eroding to an extent the cost advantages in highly knowledge-dependent technology sectors. "The cost savings will ultimately really come for businesses dealing with volume, whether this is clinical trials or manufacturing," he says. "That's simple supply and demand." 

Man's advice: "Pay enough attention to risk and infrastructure and don't build a house of cards. The burning desire for a 'quick win, fast money' as seen in the Chinese real-estate market may undermine the original goal of sustained growth." 

The companies founded by "overseas returnee" entrepreneurs play a key role in China's life science world.  Most of the Chinese students who came to the United States in the 1980s and 1990s to pursue graduate degrees in biology or chemistry established their scientific careers at pharmaceutical and biotech companies or academic research institutes. A small but growing number have found a second passion in the business side of healthcare. Many returned to school for an MBA or JD degree, while others found opportunities in business and management.  			

Back in China, armed with Western education and corporate experience, the returnees are bridging the gap of understanding between Western and Eastern business cultures. Their companies have brought new ideas and modern business paradigms to China's economy—and they often represent the best investment/collaborative opportunities for US and European companies. 

One of the earliest returnees is Kevin Chen. Born in Shanghai, Chen graduated from East China Normal University in Shanghai and received his master's from Shanghai Biochemistry Institute before coming to the United States in 1985. After receiving his PhD from the University of Minnesota and doing postdoctoral training at Caltech, Chen held positions at MIT and DuPont and was hired in 1997 to establish a research center in Beijing for Novo Nordisk.  

Today, Chen is president of a pair of Chinese companies. South Gene Technology (SGT) is the commercial arm of Shanghai's National Human Genome Center (NHGC), a major center for Chinese genomic research. "SGT is equipped with high-end high-throughput genotyping equipment and has the capability to churn out high-quality data at very competitive cost," Chen says. "We have the ability to access disease-associated genes discovered by NHGC and patient samples from our wide network with hospitals and universities." In addition, Chen heads Shanghai IgCon Therapeutics, a joint venture between SGT and California-based Genetastix that pursues therapeutical human antibodies.  

Ge Li, another returnee, founded and runs WuXi PharmaTech, a Shanghai-based company specializing in contract chemistry research and product development services. Li grew up in Beijing, received his bachelor's degree in 1989 from Peking University and his PhD from Columbia University. He was one of Pharmacopeia's founding scientists and gained valuable experience in small-molecule drug discovery and running a successful biotech company. Many of WuXi's senior managers share similar backgrounds. For example, Shuhui Chen, the company's recently hired CSO, formerly served as senior research scientist and research adviser for Lilly's discovery chemistry division. WuXi PharmaTech has more than 60 pharma and biotech clients in the United States, Europe, and Japan, including 14 of the top 20 pharma companies and eight of the top 10 biopharmaceutical companies. 

"The pharmaceutical industry is facing the challenge of escalating costs and low R&D efficiency," says Liu Ye, who cofounded Beijing Honghui Meditech, another contract chemistry research service company, with a few fellow returnees from Sweden after more than a decade of education and experience at companies such as Pharmacia and Karo Bio. "Companies that can develop effective therapeutics at more competitive cost will gain an important advantage," says Ye. 

Many returnee-founded companies are involved in medicinal and synthetic chemistry, but clinical research is another key area for returnees. Because of the large patient base and relatively concentrated specialty hospitals in cities, patients (including treatment-naive patients) can be recruited for a variety of disease indications faster than possible in the United States or Europe. On average, companies can save from two to five months by conducting a Phase I trial in China. The time saving could be more significant for Phase II and III trials, says Tao Min, a returnee who founded Bio-Research, a Beijing-based contract research organization (CRO), in 2000.  

Bio-Research is undertaking an eight-year study—cosponsored by the American Epidemiology Society and the Chinese CDC—of 100,000 Chinese cancer patients to identify environmental and dietary factors contributing to the development of cancers of the GI tract. According to Min, it is inconceivable to conduct such studies in the United States, not just because of higher costs but because the greater mobility of US patients makes them difficult to follow for the length of time required. 

Though the cost of conducting clinical trials has increased in China, it is still only 40-60 percent of the cost for most indications in the US. In China, only hospitals designated by the Chinese State Food and Drug Administration (SFDA) are authorized to conduct trials. As a result, principal investigators at such hospitals often have extensive experience with Western companies. 

One of the key differences in conducting clinical trials in China and the United States is that in the United States, the sponsoring company takes responsibility for the management and results of trials. In China, the responsible party is the clinical investigator. "We work differently with investigators in China," says Min. "These doctors are thought leaders in their own field and are extremely busy people. We need to be particularly service oriented and make the PI's work less cumbersome."  

Min's advice to Western biotech/ pharmaceutical companies interested in conducting clinical trials in China is to have the right attitude and refrain from cutting corners. The Chinese SFDA modeled many of its regulatory standards and procedures after those of the US FDA; therefore, Western companies need not be overly nervous about the process in China. Having the right attitude means following SFDA instructions and processes instead of trying to bypass steps by using connections. 

In the past few years, a small number of US companies have successfully out-licensed clinical-stage or earlier compounds to Chinese biotech companies. Peregrine Pharmaceuticals, based in Tustin, California, is an excellent example. Peregrine licensed an Iodine-131 radio-labeled Tumor Necrosis Therapy (TNT) monoclonal antibody that was indicated for a type of brain cancer to Medipharm Biotech, an antibody therapeutics company based in Shanghai. Collaborating with Peregrine and its subsidiary Avid BioServices, a CMO, Medipharm received Chinese regulatory approval for an advanced lung cancer indication in August 2003, becoming the recipient of the first radio-labeled antibody approval in China.  			

The Chinese approval came before Peregrine initiated US Phase III studies for the drug. As a result, Peregrine can access robust efficacy and safety data from its Chinese partner, potentially lowering the risk of US development. Peregrine and Avid, meanwhile, are working with Medipharm to establish a cGMP facility to produce antibody therapeutics commercially in China. 

Another recent example: In July, StarVax, an early-stage therapeutic vaccine developer in China founded by returnees, announced a licensing and codevelopment deal with Mologen, a publicly traded German biotech. Under the deal, StarVax is paying Mologen 1 million euros, plus milestones and royalties to license its DNABarrier II technology in treatments of several major cancers in China and other Eastern Asian markets. Mologen will pay StarVax 0.8 million euros for its clinical development program, performed in China according to international standards. 

"This is one of the first international biotech-biotech deals involving a Chinese company," says Burghardt Wittig, Mologen's CEO. "For Mologen, this deal is significant in terms of future access to these rapidly growing Chinese and Asian markets. At the same time we will gain clinical data that will multiply for Mologen the value and probability of a licensing deal with western pharmaceutical companies." 

Yiyou Chen, StarVax's CSO and president, was educated in Beijing and Utah and worked as a scientist at Genencor in the San Francisco Bay area before returning to China in 2003. His goal was to build a biotech company from scratch, by leveraging his overseas experiences. His partner in creating StarVax was Justin Chen, a US-trained lawyer with experience in IP and corporate transactions, and now the company's CEO. 

Opportunities in Traditional Chinese Medicine

To date, Chinese companies have mostly in-licensed compounds from the Western world, but companies looking to license novel compounds from China will find an increasing number of opportunities in the next three to five years. Some of the most interesting are expected to come from the area of Traditional Chinese Medicine (TCM). 			

TCM products account for about one-third of Chinese pharmaceutical sales. These products are typically herbal formulations and are available for many conditions, including serious chronic conditions such as hepatitis and even cancer. The Chinese government has historically promoted TCM research and development as an integral part of Chinese culture and a symbol of national pride. In 1996, the government launched the TCM Modernization and Technology Commercialization Action Plan to promote the study of TCM using modern technology and techniques.  

Chinese herbal medicines have a long history of use and strong, if anecdotal, evidence of effectiveness. Many take advantage of the synergistic action of certain plants or ingredients, much like the drug cocktails used in Western medicine. The vast resource of Chinese herbs with well-documented medical use and cultivation could become a hidden gold mine in complementing traditional Western approaches to drug discovery.  

Multinational pharmaceutical companies are eying this gold mine. In the past three years, Shanghai Institute of Materia Medica (SIMM) in partnership with Novartis has isolated 1,828 natural compounds from Chinese herbs for treating a wide range of diseases, including diabetes, cancers, and central nervous system disorders. The two organizations recently extended their research agreement through 2007, by which time they expect to isolate another 1,500 new compounds.  

A few companies have made significant strides in developing therapeutics derived from traditional medicine with the scientific rigor and sophistication of Western medicine. In 1998, for example, PolaRx Biopharmaceuticals, an early-stage US biotech company, obtained commercial rights for arsenic trioxide, a small-molecule compound developed to treat acute promyelocytic leukemia (APL). Arsenic trioxide, originally developed by a Chinese medical school from a TCM compound, has been found effective in treating APL, which affects about 2,000 new patients each year in the United States. 

PolaRx set an industry record by obtaining FDA approval in 30 months after the first US patient received treatment in a corporate-sponsored clinical trial, beating the record set by GSK's Gleevec (imatinib). PolaRx was later acquired by Cell Therapeutics Inc. (CTI), a publicly traded biotech company in Seattle that develops oncology drugs. CTI's product, Trisenox, generated more than $22 million in revenue last year and is poised to gain approval for additional cancer indications.  

At least two more compounds based on TCM are currently in development: 			

 A researcher from the Connecticut Institute for Aging and Cancer (CIAC) has successfully developed an herb mix for prolonging the survival of patients with advanced nonsmall  cell lung cancer. This product is the first health-improving anticancer product and composite herbal mix funded by NIH to enter a multicenter, FDA-supervised Phase III trial. Interestingly, FDA is allowing the product to be sold as a dietary supplement while the trial is in progress, significantly lowering the cost of clinical development.  

 SIMM has identified a novel cholinesterase inhibitor from a Chinese herb that shows efficacy in Alzheimer's disease. SIMM has licensed the compound, ZT-1, to Debiopharm, a Swiss pharmaceutical company that is conducting Phase II clinical trials.

In the future, there is likely to be an increasing number of therapeutics derived from both single-ingredient and combination-ingredient herbal formulations. International alliances in the R&D and commercialization/modernization of TCM may well reap big dividends.  

When companies consider venturing into China, their greatest concern typically involves intellectual property protection. Historically, most Chinese pharma companies lacked R&D capabilities and produced undifferentiated generic drugs, competing primarily on price. Before 1993, China did not grant drug patents. New drugs were quickly copied, often by several local companies, causing price erosion and loss of profits. For this reason, multinational pharma companies have hesitated to introduce innovative drugs for fear of losing control and not getting proper protection for valuable assets.  			

China's entry into the World Trade Organization in December 2001, however, coupled with the Chinese government's desire to attract foreign investment and its mandate to protect the country's own "high technology content" industries, has definitively improved IP protection and enforcement in the past few years.  

 enhance protection of intellectual property rights by enforcing foreign and international patents in accordance with the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), which mandates at least 20 years of drug patent protection. 

  increase foreign companies' participation in the Chinese pharmaceutical distribution industry. By the end of 2004, China's entire retail and wholesale drug markets will be open to overseas entities, after an initial opening in selected cities. 

 comply fully with international regulatory standards. This includes making China's regulatory agencies transparent in their decisions on drug approval. 

 reduce tariffs on imported pharmaceuticals from 9.6 percent to 4.2 percent on average. 

Says Doug Olson, an IP lawyer with the firm of Paul, Hastings, Janofsky & Walker: "China is working hard to make patent protection in China the functional equivalent of Western patent systems. Although the Chinese court system does not yet appear to grant damages on the same scale as in the US, injunctions to stop infringement are routinely granted."  

China's large patient base and concentrated specialty hospitals make it easier to recruit patients for clinical trials in than in the United States. On average, companies can save from two to five months by conducting a Phase I study in China.

Unleash the Dragon

In an effort to save around Â£370 million ($685 million) a year on its soaring drug bill, the UK government has negotiated a new Pharmaceutical Price Regulatory Scheme (PPRS) that cuts the prices of branded drugs by an average of 7 percent. In spite of its name, the PPRS actually regulates pharma companies' profits, rather than the prices of individual drugs directly. The scheme is voluntary, but companies making branded products that decide not to join are subject to a separate, statutory scheme. 

The deal is a result of negotiations held every five years between the UK government and the Association of the British Pharmaceutical Industry (ABPI). The 1999 round led to a 4.5 percent cut, which followed a 2.5 percent reduction in 1994. The new agreement goes into effect January 1, 2005. If a company exceeds the level of profit it is allowed, it will have to repay that excess to the government.  

Despite the agreement, ABPI President Vincent Lawton says, "The price cut is unnecessary, given that medicine prices have fallen in real terms by some 15 percent over the past 10 years and that the National Health Service's medicines budget is remaining steady at about 12 percent of expenditure. Yet, because it is a five-year agreement, it offers a degree of stability that is important to an industry that works very much in the long term." 

The trade organization says it was able to go along with the cuts because of the other measures being introduced as part of the agreement. Companies are currently able to offset 23 percent of their R&D spend against their permitted profits, and that figure will rise to 28 percent. Financial incentives will also be implemented for research into pediatric medicines. "This new deal is a win-win," says UK Health Secretary John Reid, MP. "It is good value for the NHS and the taxpayer, and it is good for the industry because it provides an incentive for research and innovation." 

The companies must decide how the price cuts will be applied, because they do not necessarily have to be 7 percent across the board. Rather, the companies can skew the reductions toward different products, as long as the overall reduction is 7 percent. That means if a company has a product that is about to go off patent, it can enact a large price cut for that brand to stave off generic competition and still offset the loss by applying smaller price reductions to newer drugs. 

In another change, the sales promotion allowance will be replaced by a marketing allowance. Although the companies can spend as much as they like on marketing, they will be able to write off  Â£1 million ($1.8 million) of those expenses, plus 4 percent of sales and a small additional allowance for each molecule. The amount of "information expenses" that can be itemized has also risen, to 4 percent of sales from 1.6 percent, and this can now include the provision of information to government bodies such as the National Institute for Clinical Excellence. 

Some financial assistance has been provided for smaller companies as well. The threshold at which they routinely have to report their financial data was raised to Â£5 million ($9.2 million) from Â£1 million ($1.8 million), which eliminates some smaller companies from the process altogether. The BioIndustry Association, however, is concerned that the price cuts will disproportionately penalize the smaller companies because their fixed costs are proportionally higher and their range of products is smaller. ABPI has also come under pressure from some of its smaller members, who are unhappy that the balance is too far in favor of Big Pharma. 

The price reductions in the UK are not as severe as those instituted in Germany earlier this year, in which the government demanded a 16 percent cut in the prices of many products. But the new agreement is a further indication that drugs prices are under pressure worldwide, as healthcare providers and payers look to rein in costs.  

Although the UK represents only 4 percent of global drug sales, it is an important R&D center, and companies are keen for the domestic market to remain competitive for investment. Although the new PPRS will save the UK government an estimated Â£1.8 billion ($3.3 billion) over the life of the agreement, if it leads to more research emigrating to more friendly financial environments such as the United States, the arrangement may ultimately prove to be counterproductive.

 global correspondent. She can be reached at 

World News

The British trade association says the cuts are unnecessary because drug prices have fallen in real terms by 10-15 percent during the last 10 years while the UK government's budget has remained steady.

When Is Enough?

For pharma companies and insurers, the re-election of George Bush was good news. Much to their relief, it ends the threat of legislation that would allow the federal government to directly negotiate drug prices with Medicare drug plans.  

Continued GOP control of the government also will make for a smoother implementation of the Medicare prescription drug benefit and many complex provisions in the Medicare Modernization Act (MMA). Health and Human Services (HHS) officials pushed hard for the Medicare reform legislation and have a high stake in establishing workable regulations and policies. 

Major initiatives to expand healthcare coverage to the uninsured or reform Medicaid are low priorities at the Bush White House. Social Security and tax reform will be the administration's main domestic policy initiatives. President Bush is expected to offer additional tax incentives for individuals and small businesses to obtain health coverage. The administration's main strategy is to rely on private insurers and employers to make available health savings accounts and other more affordable coverage options.

Postelection polls show that healthcare was eclipsed by other issues during the presidential campaign. Only 6 percent of voters made their Election Day choice based on health issues, while 23 percent selected a president who reflects their "moral values," according to a postelection survey by pollster Whit Ayres. Almost 80 percent of the voters consider healthcare issues very important, but most are concerned more about affordability than about expanding coverage of the uninsured. 			

Although many elderly voters are confused about the new Medicare drug benefit and managed-care choices provided by the MMA, seniors seem to consider the new program worth trying. Bush actually did better among elderly voters this time, and efforts by Sen. John Kerry and Democrats to denounce the Medicare pharmacy benefit as inadequate and a giveaway to rich pharma companies and insurers evidently did not sit well with the public; that strategy may have even cost Senate Minority Leader Tom Daschle (D, SD) his seat. Voters complained that the presidential debate on healthcare was not specific enough and failed to offer real solutions, a perception that hurt Democrats.  

That said, rising healthcare costs and prices will draw intense scrutiny from Republicans as well as Democrats and may translate into policies for restraining healthcare spending growth. The administration faces a record budget deficit and escalating outlays for the Iraq war and counterterrorism as well as new Medicare benefits for more than 40 million elderly Americans. 

The launch of the Medicare pharmacy benefit in January 2006 will focus more public attention on drug costs, utilization and marketing. (See "Rolling Out the Regs,") Medicare drug plans will be establishing formularies, posting negotiated prices, promoting treatment protocols, and tracking adverse events and outcomes more thoroughly. All these actions are likely to shape prescribing practices and utilization of new products. Although prescription drugs account for only about 12 percent of total healthcare outlays, medical products are a growing and highly visible portion of spending.  

Policy makers are under pressure to make new therapies more affordable and accessible. They will gain more clout to do so as the government becomes the purchaser of more than half the prescription drugs used in the United States. Despite Republican rhetoric about relying on free-market competition, the administration may find itself championing a range of cost-control initiatives—including more flexibility in allowing imports from abroad.  

While broad health reform is not on the Bush policy agenda, a number of health issues important for pharmaceutical companies are likely to emerge. These include:  

 Stronger Republican control of the Senate could open the door for action on medical malpractice reform. Physicians have been pressing for caps on liability awards as a way to curb soaring malpractice insurance premiums, but proposals have been stuck in the Senate for years. During the campaign, Bush and other Republicans blamed malpractice awards for pushing up healthcare costs, a trend that also encourages defensive medicine and costly medical procedures. A majority of voters seem to agree that malpractice litigation raises costs, as seen in the adoption of several state referendums capping malpractice payments.  

An early test for liability reform may surface in proposals to expand Project BioShield. Sponsors of legislation to boost federal support for research and development of new counterterrorism vaccines and treatments want to provide liability protections for manufacturers of products likely to be used in high-risk situations. Democrats have opposed such safeguards as a giveaway to Big Pharma, but a more conservative Senate could prevail. 

Even though Democrats failed to parlay support for increased purchase of drugs from Canada and other Western nations into victory, the drug import campaign is not likely to die down. For both political and fiscal reasons, the White House will be looking for ways to identify "safe" foreign sources of less costly medicines. Several of the new Republican senators championed broader drug importing as one way to expand access to affordable medicines and will be seeking to fulfill their promises.  

The Bush victory puts on hold efforts to expand federal support for research that involves destroying human embryos. Instead, research will shift more to private and state programs. California voters approved an initiative to provide state funding for stem cell research, and other states may follow suit. Moderate Republicans in Congress hope that the California action will spur legislation to modify the Bush policy, but the President has little reason to revise his current stance.  

 As in the past, the Bush administration will look to tax breaks and market incentives to provide more options for individuals to obtain healthcare coverage. The prime vehicle is the tax-deductible health savings account coupled with a high-deductible, lower-cost insurance plan. With most of the nation's 45 million uninsured holding jobs, Republicans want to encourage employers to broaden coverage for workers as the best way to attain universal coverage. Any great expansion of these programs, however, would be costly in terms of tax losses that could add to the budget deficit. 

Washington Report

Expanded coverage for the uninsured and Medicaid reform are low priorities at the White House.

Four More...

I got an e-mail the other day from a journalism student, asking for an interview. "I'm currently trying to write an article for my advanced reporting class about the lax relationship of the FDA and the industry since the passage of the Prescription Drug User Fee Act." When I wrote back, I suggested that maybe he'd end up with a  better story if, instead of starting with the assumption that FDA had grown lax, he began by asking whether it actually had. 

Coming to a conclusion before doing the research is a classic reporter's error. It's no surprise when a student falls into it that trap, especially when approaching a topic as complex as drug regulation. What's disappointing is to see how the mainstream media are committing exactly the same error in covering the recent flaps over antidepressants, Vioxx, and the like. 

 maps out a critic's case against FDA: The number of adverse events reported to the agency is up. At the same time, the number of withdrawals of major drugs is down compared with the period 1996-2001. The number of warning letters on advertising has dropped. Obviously then, drug safety is going to hell in a handbasket. 

I hardly have to point out what's wrong with this "evidence." The number of adverse events reported to FDA is 

 to be up, as FDA has improved its reporting system and demands more postmarketing studies. If anything, the worry is that there still aren't enough adverse events being reported. The number of withdrawals may be down, but it's down from a four-year period when withdrawals were unprecedentedly high. And as for warning letters on advertising, the comparison the 

made is with the period immediately following the introduction of direct-to-consumer advertising. If things worked as they should, the number of warning letters 

to be dropping as companies learn the rules. The facts may be facts, but when you get right down to it, they don't tell us much. 

 noted at least some of the problems with the numbers—in the same pro forma way that the newspapers print the convicted killer's "I didn't even have a gun, and, besides, it wasn't loaded." The accusation was the news. The rest was just "getting the other side." 

Getting both sides of a story is important, but you have to be smart about figuring out what the two sides are. When I read the papers these days, it seems many of them have decided that it's the industry and the FDA on one side, and the embattled defenders of patients on the other. Fair enough, but there are two other sides that are equally important, and as near as I can tell, only one of them is getting to speak.  

Maybe that's because the two sides don't represent two different groups of people: they represent two competing ideas within almost all of us. One idea is that safety is the only thing that matters, and we should never have to take a risk when we take our medicine. The other is that when our own health is at stake, we should be able to make our own decisions about medicines, and the government should butt out. 

A complete contradiction? Sure. But that seems to be how people really think. They'll howl that Vioxx was left on the market too long, then they'll turn around and howl when Amgen, convinced that its experimental drug for Parkinson's disease is both ineffective and dangerous, halts trials and cuts off patients from further supplies.  

People are entitled to contradict themselves, of course. And ambivalence can be the basis of sound policy. (What is FDA's risk-management approach if not an attempt to respond to our desire to have it both ways?) But people need to understand that the conflict in the Vioxx case and others is not just between the industry and its gadflies. It's a conflict within.

is Pharmaceutical Executive’s editor-in-chief and can be reached at  

From the Editor

Journalists try to tell both sides of a story. That's fine when there are two groups in conflict. But how do you tell the story right when the real conflict is between the two halves of one ambivalent opinion.

Telling Both Sides

Science fiction writer Arthur C. Clarke's 

Third Law states: "Any sufficiently advanced technology is indistinguishable from magic." Paul Ehrlich, the Nobel Prize-winning pharmaceutical pioneer, used to say, "We must learn to shoot microbes with magic bullets." This year's 25 Most Attention-Getting Investigational Compounds (MAGIC), are all products of advanced technology—"bullets" that may well appear magical some day. But there are no tricks involved. Chosen by pharmaceutical analysts and consultants asked to name the late-stage products that caught their notice (candidates had to be beyond Phase II but not yet launched, and new uses for known products were counted as new), they embody the hopes and hard work of countless people. 			

Keeping in mind the effort, the uncertainty, the inevitable twists and turns and ups and downs, it might be said that every molecule tells a story. Here then, out of hundreds swimming upstream through the pipeline against all odds, are 25. 

The most popular selection in the MAGIC 25, Acomplia (rimonabant)  has been dubbed the antimunchie drug because, as a cannabinoid CB1 receptor antagonist, it blocks sites "believed to mediate hunger responses when individuals smoke marijuana," says 2Value analyst Marc Samet, PhD. This mechanism has produced "promising clinical data for two indications—obesity and smoking—both large consumer-friendly spaces," says Mara Goldstein, pharmaceutical analyst for CIBC World Markets. What's more, subjects in a recently reported two-year trial not only lost an average of 19 pounds, their cardiovascular profiles improved. And patients who stayed on the drug tended to maintain their weight loss, while those who went off it gained theirs back. Says David Moskowitz, an analyst with Friedman, Billings, Ramsey:"There may be some nervousness in the wake of fen-phen, but there is clearly a need for a way to reduce weight safely, especially since abdominal fat is an important indicator of cardiovascular risk."  

Acomplia is "not an extraordinary breakthrough," in the view of David Goldstein, MD, PhD, formerly with Eli Lilly and now a consultant and a member of the board of the American Society for Clinical Pharmacology and Therapeutics. But it is "a novel mechanism that will add to physicians' arsenals and allow them to try multiple treatments for obesity." Although, he adds, the efficacy of these combinations "has not been tested." He expects "marginally better results from Acomplia compared with other recent products," and thinks it will "probably get off to a hot start—people are hungry for something new." But then "reality will set in: It won't make people thin." Goldstein also foresees three potential problems: "Studies show an increase in infections in year one, possibly involving immune modulator CB2. Cannabinoids are analgesics, so those taking painkillers along with Acomplia may find their effects blunted. Finally, there are hints that Acomplia may be accompanied by an increase in anxiety and depression."  

Acomplia may appear formidable, but analysts warn that it is entering a crowded smoking cessation market and is also up against several well-entrenched statins.  

A New Drug Application (NDA) for an obesity indication is expected to be filed as early as next year.  

Called by analyst Moskowitz "an effective new molecule" for the treatment of Type 2 (noninsulin dependent, adult onset) diabetes, Exenatide was discovered in a protein found in the toxic saliva of the beaded lizard, a close relative of the Gila monster. Exenatide is the first in a new class of drugs called incretin mimetics. A glucagon-like peptide-1 (GLP-1) agonist, it stimulates insulin secretion to improve blood glucose control. But, Moskowitz says, "Unlike insulin, it does so without incurring the risk of hypoglycemia [low blood sugar]." In addition to that, Exenatide appears to promote weight loss—which would in many cases lessen the severity of diabetes—something insulin impedes. Exenatide has been found effective for Type 2 diabetics not taking insulin who have had no success with current oral medications.  

There is one possible drawback, Moskowitz says: "As a twice-daily injectable, its growth could be slowed by resistance to the delivery system." There is also competition coming. Novo Nordisk has its own GLP-1 agonist Liraglutide (NN-2211) in Phase II, and Merck and Novartis are working on oral agents with a similar mechanism of action (MOA). An NDA was filed in June and was accepted for review by FDA in September. A decision is anticipated by the end of first quarter 2005. 

A treatment for insomnia, a condition that affects 40 percent of US adults, indiplon is a second-generation nonbenzodiazepine sedative hypnotic that functions as a GABA

 receptor agonist. Its mechanism of action is similar to Sanofi-Aventis' best-selling Ambien (zolpidem), Jones Pharma's Sonata (zaleplon), and Sepracor's forthcoming Estorra (eszopiclone). But indiplon, perhaps because of its tendency to bind selectively with the alpha-1 subunit, believed to be the specific subsite responsible for promoting sleep, has shown little, if any, residual hangover effects or evidence of withdrawal or rebound insomnia. In addition to its clean side-effect profile, indiplon's biggest advantage may be Neurocrine Biosciences' choice of marketing partner: Pfizer. The two are collaborating on clinical development and promotion in the United States. Pfizer has exclusive rights to market and develop indiplon elsewhere. An NDA for indiplon IR (immediate release) was filed in October and one for a modified release formulation last month. A decision is likely in the middle of 2005. 

One of three carryovers from last year's Pipeline Report—it topped the list—lasofoxifene is a potent, non-steroidal, tissue-selective estrogen receptor modulator (SERM) being tested for the prevention of postmenopausal osteoporosis and breast cancer. Unlike estrogen, which inhibits bone loss but raises the risk of uterine cancer, it shows signs of being an anti-cancer agent. Discovered by Ligand and Pfizer, the drug is being developed by Pfizer under license in accordance with the resolution of a contract dispute.  

An NDA was submitted in October for postmenopausal osteoporosis, and a product launch is forecast for 2006-2007. Phase III trials are under way to test its effectiveness in reducing the risk of breast cancer, vertebral fractures, and cardiovascular disease.  

Lipitor/torcetrapib [atorvastatin/torcetrapib] 

Acombination of Lipitor (atorvastatin) and torcetrapib is "the first major therapy to adopt a dual approach to lipid-profile management," says Albert Rauch, PhD, an analyst with A.G. Edwards & Sons. The former lowers LDL ("bad" cholesterol), and the latter is expected to raise HDL ("good" cholesterol). It "could set a new standard in the $20 billion cholesterol reducer market and add years of exclusivity to Lipitor," says Mara Goldstein. Moskowitz thinks it has the potential to be bigger than Lipitor alone, as well as expand the market beyond $20 billion. "Initially, it will enhance Pfizer's revenues, then after Lipitor's patent expires in 2011, it will stabilize them,"she says. "Pfizer could have the cholesterol lowering market to itself."  

 Pharmaceutical Executive Pipeline Report

Torcetrapib "inhibits cholesteryl ester transferase protein (CETP), an enzyme responsible for LDL-mediated control of cholesterol synthesis," Samet explains. Now in a massive Phase III study—the largest clinical trial ever—torcetrapib, in combination with Lipitor, boosted HDL by 60-100 percent. But this, Samet points out, "required twice-daily dosing, which may slow the launch of a combination pill." However, he adds, "There are few drugs near the market that can significantly elevate HDL, which provides a unique marketing advantage for Pfizer's franchise." Winton Gibbons, an analyst at William Blair & Co. agrees: "The marketing advantage is all Pfizer's. Roche has no statin with which to package JTT-705, the HDL-raising drug it in-licensed from Japan Tobacco—though it could conceivably make a deal for one." What's more, he says, "Results of Phase II tests showed that Lipitor and torcetrapib had genuine synergy: Patients' lipid profiles were better when the drugs were taken together than when taken alone." Finally, Gibbon says, "Lipitor already has a broad claim to prevent cardiovascular disease in its original label, while Roche will have to earn it at considerable expense and over time." An NDA filing is expected before 2006. 

Vatalanib is an anti-angiogenic RTK (receptor tyrosine kinase) inhibitor. It disrupts intercellular communication through a well-known signaling pathway that has been implicated in the way cancer cells create new blood vessels from existing ones (angiogenesis). In particular, like Genentech's Avastin (bevacizumab), it blocks the vascular endothelial growth factor (VEGF) receptors, and so deprives certain tumors of the blood supply they need to grow. However, Avastin is taken intravenously, while PTK 787 is formulated as a pill. Phase III trials are ongoing. An NDA filing may be expected before the end of 2005.  

Ruboxistaurin, "the first treatment to address the microvascular complications of diabetes affecting the nerves, eyes, and kidneys," according to Rauch, "answers a huge unmet medical need." Six Phase III trials are under way. So far, initial clinical data has been positive for a variety of diabetic complications. 

Ruboxistaurin is a protein kinase C beta (PKC beta) inhibitor. Numerous studies to date have highlighted diabetic activation of PKC as a mechanism leading to the development of serious microvascular complications.  

Ruboxistaurin promises to map entirely new medical terrain. A recent study on diabetic neuropathy from Decision Resources predicts that its launch will shift the market from pain control to disease modification. 

In late November, Tysabri (natalizumab), the drug formerly known as Antegren, received approval for the prevention of multiple sclerosis (MS) relapses. That's also when it was renamed at FDA's request. An NDA had been filed on the basis of first-year results in two ongoing two-year Phase III trials in which Tysabri monotherapy reduced the rate of relapses by 66 percent compared with placebo—twice as effective as current drugs tested in other  trials (which may void comparison).  

Pharm Exec's Pipeline Report is packed with 25 of the year's most eye-catching experimental drugs. What's their secret? No smoke or mirrors-just innovative science, therapeutic value, and good business sense.

Pharmaceutical Executive-12-01-2004