Personalising medicine

pharmafile | August 1, 2005 | Feature | Research and Development |   

Hard times have hit the drug development industry. Faced with declining returns and the apparent waning of blockbusters, coupled with the aggressive onslaught of generic competition, how can pharma recapture its golden past? In the current climate of candidate drought, there doesn't seem to be a simple, single means available to drug developers to plump up their pipelines.

Dr Joel Dobbs, executive in residence and programme director, Pharmaceutical Technology Management at the Stevens Institute of Technology in New Jersey, explains how, today, most companies are engaging in a multi-pronged approach involving internal research, developmental partnerships and compound licensing, usually from smaller industry counterparts or academic labs.

Innovate to survive

This modern, mixed approach to drug development is echoed by Wyeth's head of research and development Dr Robert Ruffolo, who says: "Most large pharmaceutical companies, including Wyeth, fill their pipelines through internal discovery of new drugs. In addition, most large companies also look for opportunities externally and attempt to supplement their pipelines."

"In today's world only the innovative survive," says Dr Dobbs. "A new drug must represent a significant therapeutic advance."

The Tufts Centre for the Study of Drug Development agrees – their 2005 Outlook report looking at future drug development trends observes: "R&D strategies that strive to attain a best-in-class status for new drugs or, at the least, clear advantages over existing therapies with patient subgroups or particular indications, will dominate."

Which therapy areas will pharma be focusing its future drug development efforts on? Cancer is certainly fixed at the hub of next-generation R&D. According to Business Insights, drug development projects in cancer outnumber the drug candidates in all other therapy areas combined.

The five major causes of death in the US have remained largely unchanged over the past 50 years. "Innovative therapies that offer cures or dramatic improvements in the course of any of these – heart disease and cancer for instance – will have a significant market potential," adds Dr Dobbs.

On the other hand, concern has been voiced that the industry's enthusiasm for anti-infectives is ebbing away and that legislative incentives may be necessary to spur future drug development in this area. Wyeth's vice president of research Dr Stephen Projan said recently: "The investment equation is shifting away from treating acute disease towards chronic disease, towards larger markets." As a result, many of the big pharma companies "have stopped or have greatly curtailed their anti-infective drug discovery work, especially for antibacterials."

As well as striving for innovation in traditional areas, a new wave of drug development, driven in part by access to the entire human genome, is touching on previous wilderness areas in medicine.

"We believe that we can now attack diseases that before we couldn't even dream of treating," remarks Dr Ruffolo. "For example, Wyeth is working on drugs for muscular dystrophy, stroke, a variety of different cancers, Alzheimer's disease and chronic obstructive pulmonary disease, to name but a few. This is good news for us in the industry, but more importantly, it is even better news for patients."

Dr Dobbs agrees that treatments for orphan diseases where there are no acceptable therapies present opportune targets for pharma companies to aim at however, the market for many of these medicines may be small.

"In the end, we do need to generate sufficient revenues from our new drugs to fund research," notes Dr Ruffolo. In order to encourage future focus on orphan diseases, pharma companies agree that the onus will rest on governments and regulatory bodies to continue to provide incentives for companies to develop drugs for these rare conditions where recovering R&D costs is unlikely.

At the other end of the spectrum, lifestyle drugs continue to be close to drug developer's hearts. Dr Dobbs believes that as the baby boom cohort ages, the market for lifestyle medications will continue to grow. The success of Viagra and its follow-on products, plastic surgery, Botox, laser vision corrective surgery and treatments for baldness have shown the willingness of people to pay from their own pockets for lifestyle therapies that actually work.

"This could be the last segment of the pharmaceutical market that retains immunity from the economic forces that are challenging the industry today," Dr Dobbs concludes.

'Nichebusters'

There are considerable financial fruits to be harvested from sowing the seeds of research into niche markets. Novartis' niche proteomic product, Glivec, generated $1 billion in global sales in 2003, and a similar amount has rolled into Roche's coffers from worldwide sales of its niche drug Herceptin for HER2 positive metastatic breast cancer.

Many agree that blockbusters have had their time in the sun and that the niche product will soon step out of the shadows. From 2005 to 2008, total blockbuster sales are predicted to swell by a mere 1.6%, a considerable drop on the forecast 9% growth in the previous thrre years.

Business Insights new report, Beyond the Blockbuster Drug, depicts the industry as teetering on the brink of a 'Nichebuster' revolution which is geared to propel future market growth and give rise to the leading medicines of tomorrow.

The report predicts: "The competitive pressures and falling R&D productivity will instigate a new pharmaceutical model that replaces the unsustainable blockbuster model with personalised medicine and the 'nichebuster'".

The anticipated change in drug discovery is a move away from the small number of chronic diseases which have traditionally been the focus of big pharma companies towards other less prevalent medical conditions. If this shift happens, orphan drug development may yet come into its own.

Human Genome Project – fantasy or reality?

The Human Genome Project has started to change the landscape of drug development, but it is still early days. While genomics has yielded an explosion in the number of molecular targets, the bulk of the work remains – understanding the purpose and function of the different components and their link to disease pathology.

Dr Dobbs likens the completion of the sequencing of the human genome to the discovery of the Dead Sea Scrolls in the late 1940s. Most archaeologists knew that this was a significant discovery but, until the scrolls could be translated and studied, no one could really appreciate their significance. "This is where we are with the human genome," says Dr Dobbs. "We are at the beginning of a long and highly significant period of discovery."

Personalised medicine

A recent Reuters Business Insight report, The Future of Personalized Medicine, predicts that proteomics has the potential to slash both drug development times and attrition rates. By cutting development time by three years and doubling the number of successful NDAs, Reuters predict proteomics could shave R&D costs by as much as 30% per year. The new proteomics trend could also help companies target niche markets and harvest the manifold financial rewards.

Somewhat surprisingly, the industry has been slow to seize on the latent potential of proteomics. However, Reuters believe this picture will shift in the future as strategic alliances and acquisitions assume a central position in fuelling the industry uptake of proteomics.

There is clearly a wide gulf between employing proteomics in drug development and the eventual advent of an era of personalized medicine – although the potential is promising. According to the Reuters report: "Personalized medicine could dramatically change the marketing environment as targeted therapies and diagnostic biomarkers play a greater role in determining treatment patterns."

Dr Ruffolo thinks that personalized medicine, although not yet a common reality, should certainly not be written off as a nebulous dream. Indeed, he describes Wyeth's cancer drug Mylotarg as a current example of personalized medicine which is already being used to treat patients with acute myelogenous leukaemia (AML).

Mylotarg is like a 'smart bomb' consisting of a potent cytotoxic agent linked to an antibody directed against a cell surface protein, CD-33, found only on cancer cells in AML.

'The patient with AML can have his/her cells analyzed for the presence of CD-33, and if it is present, can be considered a candidate for Mylotarg. So this is personalized medicine at its best," says Dr Ruffolo. "I suspect that by the end of this decade there will be many more examples of personalized medicine, but I don't think it will be common practice for most of the common diseases for quite some time."

Dr Dobbs agrees that the future of customized therapies tailored to a patient's genetic profile, although a promising premise, is probably several years away in reality. Business Insights predicts 2025 as the year in which personalized health maintenance programmes may be created, spawned off the back of development of a targeted medicines sector within the industry.

Biomarkers are one of the buzz words of today's genome generation researchers. Greater understanding of genetics has fuelled increased use of these biological indicators in drug development across all therapy areas. "Virtually every major drug and biomedical companies is now engaged in biomarker research," reports Dr Mario Ehlers, chief medical officer at Pacific Biometrics, a dedicated applied research facility based in Seattle.

Along with bioassays, computer modeling techniques and validated surrogate endpoints, biomarkers are key development tools which are helping the industry rise to one of its major challenges – early termination of unpromising R&D projects. According to Tufts, this is an imperative if a pharma company hopes to remain competitive. Looking at the latest trends in drug development, Tufts notes that "rapidly rising R&D costs has led economics to gain ascendancy as a major reason for killing unpromising products in the R&D pipeline".

This emphasis on economics is hardly surprising given that, as Tufts reports, despite a huge hike in R&D spending, the actual number of new drugs and biologics being submitted to the FDA for review has been steadily decreasing in recent years. By focusing on early termination of losers in the future, drug developers will benefit from lower research costs, coupled with enhanced predictability of development cycles.

Getting together

According to Ernst & Young's Global Pharmaceutical Issues and Insights, it is concern over near-term shortage of new products and lack of robust pipelines which is causing large pharma to enter more licensing and collaborative R&D agreements for late-stage products.

Dr Dobbs agrees that licensing is one of the major burgeoning trends in drug development, being expedited by companies seeking ways to quickly close gaps in their existing pipelines and compensate for lost revenues associated with patient expirations.

"The simple truth is that most, if not all, of the large pharma companies simply cannot produce enough compounds from their internal research efforts to produce the kind of revenue needed to maintain growth into the future," he explains. "Licensing and strategic partnerships are mandatory."

Together with the increasing trend in licensing, is a parallel advance in company takeovers, where pharma businesses opt to swallow up the company with the technology/products of interest. The pharmaceutical sector closed 171 merger and acquisition deals in 2004 valued at a total of $98.9 billion.

Ernst & Young says that the declining share price of several major pharma companies in the early part of this year, coupled with other market conditions, has heightened speculation that a new series of M&As may be in the offing.

Looking to the future, Tufts believes that "Firms will face growing pressure to improve R&D productivity to get new drugs to market sooner and to develop medicines with demonstratable advantages over current therapies."

As protective periods of marketing exclusivity become ever more fleeting, the onus will be on drug developers to hone productivity in their drug development activities in order to reap maximum return on their investment.

"Productivity and quality improvements are indisputable R&D mandates for drug and biotech companies," says Tufts. "To improve their product pipelines, drug developers must address the big picture issues such as creating more innovative R&D strategies, and small picture issues such as cutting recruitment costs for patients in clinical trials."

It's a tall order and only time will tell which approach drug developers ultimately embrace, and which new trend eventually bears fruit with market success.