Explaining the Drug Drought

This is a time of deep uncertainty for the big players in the research-based industry, where the traditional metric of performance—strong profits—fails to translate to the traditional metric of reward—increased shareholder value. Most analysts attribute the disconnect to investors' lack of confidence in the industry's future, as represented by a faltering development pipeline characterized by skyrocketing risks and fewer new products with significant clinical breakthrough potential.

Eve E. Slater, M.D.

The burning question is: Is it time to declare the traditional model of drug discovery and development dead?

The question brings with it no ready answer. The exact explanation for dry pipelines and static timelines remains elusive, while the task of delivering on expectations is made harder by a convergence of external factors: a looming patent cliff, narrowing of reimbursement margins, higher pre- and post-approval regulatory hurdles, and the financial impact of US health reform, which has made the largest and most predictable of markets a blank slate for the industry going forward. Companies are responding with lateral rather than groundbreaking strategies: consolidation and alliance creation, engagement of functional service providers, "off-shoring" of clinical trials, expansion into emerging markets, and production of branded generics. These may bolster the balance sheet but do little to strengthen the underlying core competency and build R&D capacity.

Kenneth Kaitin, Ph.D

Any improvised and short-term approach such as this raises a second, broader question: What will become of biomedical innovation if Big Pharma relinquishes its responsibility in serving as the key driver of new drug development?

Private-sector R&D budgets—essential to ensuring that a pill can be taken safely by patients, for the intended clinical effect—are shrinking as the industry contracts. Reallocation of resources is also under way; the shift of monies from "R" to "D" has become unavoidable as trial endpoints become more complex, and regulatory requirements, such as risk mitigation strategies, escalate. Much of the innovation emanating from smaller biotech companies has been locked up by the big players in deals, and new venture money for cash-strapped startups is dwindling as the buyout specialists shift focus.

Without a substantive course correction, the pressures on the R&D model will constrict what remains of the pharmaceutical industry's ability to innovate. And that leads us to a third question: Will society—and patients—suffer as a result? Why can't government take on this task?

Science Moving Forward

One might conclude that, should Big Pharma stumble, the science of drug innovation will proceed elsewhere. This may be true. The discovery mantle will shift more decidedly to academia, their derivatives, or for-profit startups, and Big Pharma will simply revert to its traditional strengths: covering late clinical testing, regulatory, manufacturing, and marketing. To a large extent this is already happening. However, the long-term effects are still cause for concern. For example, will venture capitalists and other investors continue to fund startups, given the growing concern over the state of Big Pharma and what that means for a viable exit strategy? What happens when government seeks to drive disease priorities—does it have the staying power to be consistent and on point during the long pathway toward commercialization? Is disease target prioritization through public intervention necessarily better than private incentive? Is it foreordained that industry should just wash its hands of stimulating the bread-and-butter of basic discovery work?

The traditional model of drug discovery has waned in recent years, due to a focus on bolstering the balance sheet. In order for Big Pharma to uncover a new "golden age" it must regain its responsibility of being the key driver of R&D. (Getty Images / Don Bishop)

Such concerns are valid. To declare defeat and advocate a dismantling of what remains of the industry's extended R&D infrastructure (as some on Wall Street have done) could cripple the best weapon we have against the ever-changing panorama of chronic disease, which is biomedical innovation. Until we fully dissect the elements of the so-called "drug drought" and understand what is happening and why, it is premature to pronounce the traditional model "dead."

During the so-called "golden age" which culminated in the mid-'90s, over 30 new drugs on average were brought to market each year. Life-saving and enhancing new product classes abound. Statin drugs, prescribed to over 40 million Americans today, are credited with having a major impact in reducing cardiovascular morbidity and mortality. Drugs that interfere with platelet function and clotting factors have granted further benefits. The protease inhibitors that have transformed HIV/AIDS from a quick killer to a chronic disease could not have reached patients as quickly without the industry's innovative expertise in clinical certification, safety profiling, and efficient manufacturing. Likewise, the major advances in transplant surgery would not be possible without medicines to control tissue rejection. Pharmacologic cancer cures are now emerging for adults as they have over the past several decades for children. Finally, unlocking of the human genome promises targeted therapy and tailored treatments for the most vulnerable populations, as well as better health outcomes at a lower cost.

There are many therapeutic successes, yet the pharmaceutical industry is still within the crosshairs of public skepticism. The issue stems, in part, from a crisis of confidence within industry—an inability or unwillingness to stand up for a better social contract, where individual reward is evaluated against the larger benefits to society, even when such benefits cannot always be quantified. The pharma industry produces an essential good that builds on a legacy of centuries of progress in science, yet many CEOs fail to articulate the connection between what we died of yesterday and how we live today. Have the industry's leaders lost their identity as passionate innovators, for the sake of being proficient managers?

To Shape the Debate, Marshal the Evidence

It would be unfortunate to accept a future built around Big Pharma as little more than a scaled-up distribution platform. Industry should articulate the perils to future patient-centered innovation if the collaborative equipoise between academia and industry is dismantled. Biomedical innovation is not a contest of methodologies, but rather a composite national resource.

To create this fresh dynamic, the reasons that explain success and failure in industry labs must be dissected, in far greater detail than it has been to date. A suitably resourced, high-level analysis and explanation is overdue. It is up to industry to take the lead in defining problems in its own shop, and to then build a global policy consensus on how to fix them. For example, industry's chief scientists—the company heads of R&D—should state plainly as a group that more help is needed from payers, patient groups, and other stakeholders to make better decisions on what compounds to bring into development. We suspect that from this endeavor, the need for new incentive-based policies will become apparent. That need, in turn, will drive a new level of engagement—with government and other partners—for the one proven engine of innovation, which is the private research enterprise. Protecting this rich resource is good for patients and society. This opportunity must not be squandered.

Eve E. Slater, M.D., is Associate Clinical Professor of Medicine at Columbia University's College of Physicians and Surgeons. She can be reached at ees2@columbia.edu

Kenneth Kaitin, Ph.D, is Director of the Tufts Center for the Study of Drug Development and Professor at Tufts University School of Medicine. He can be reached at kenneth.kaitin@tufts.edu