Pharm Exec's 2013 Pipeline Report

Nov 01, 2012

Is the "lost decade" of declining pipeline productivity finally over? Our annual survey of analyst assessments of the state of drug development suggests so, with subtle shards of sunlight beginning to penetrate the gloom cast by the historic loss of exclusivity on more than $80 billion of blockbuster medicines since 2009, as well as the unexpected challenges in leveraging the promise of the human genome through the application of molecular biology to drug treatment.

Our discussions with a baker's dozen of investment analysts and experts provided insights that lead us to three strategic conclusions about new drug prospects for the year ahead. First, the demand from payers and patients for better evidence of outcomes has imposed new discipline on the R&D process, which is bearing fruit—our list of promising compounds clearly shows an improved correlation between development priorities and areas of real unmet medical need. Second, the emergence of biologics as the dominant area of focus suggests that the process of drug development has finally caught up with the science unleashed by the genomics revolution. Third, the commercial potential of many of these compounds are cited sufficiently to lead us to conclude that predictions of an end to the blockbuster era of "billion dollar plus" medicines are premature.

It all goes back to the traditional premise that if the clinical need is there, revenues will follow. The big overhang is whether those revenues will be accompanied by the high profit margins required to defray an equally high level of exposure risk. The irony is that, even with the resolution of the so-called crisis in R&D and a return to a more productive pipeline, the industry must still confront a gradual but irrevocable erosion of control over access and pricing for these "next generation" products.

—William Looney, Editor-in-Chief

Alzheimer's Disease: Moving Forward

Without a drug that truly modifies, if not halts, the progression of Alzheimer's disease, caring for patients in the United States alone is expected to top $1 trillion annually by 2020. Late last summer, Pfizer and J&J ended their joint development program on bapineuzumab, a late-stage monoclonal antibody targeting beta amyloid, a primary component of amyloid plaque build-up in the brains of most Alzheimer's patients. Beta amyloid appeared to be the most promising target for new drugs, which made bapi's failure all the more distressing.

Many disheartened onlookers assumed that Eli Lilly's solanezumab, a similar compound also targeting beta amyloid, was destined for the same fate. While solanezumab is not the game-changer in Alzheimer's that everyone is still waiting for, Lilly's Phase III EXPEDITION trial did evince a slowing of cognitive decline among patients in early stages of the disease. Whether or not solanezumab will eventually receive approval—and there are plenty of opinions in support of both answers to that question—what's more important is that companies working in Alzheimer's can now optimize their own development programs around Lilly's results.

"There's a difference between the fact that it got the scientists and clinicians very excited, and the fact that it's not going to be approved and be a revenue generator for Lilly," says Ben Weintraub, senior principal and director of research at inThought, a division of Source Healthcare Analytics. "The results were statistically significant but not clinically significant. But the fact that it had any effect [on cognitive decline] at all—this is the first drug that showed any hint of doing anything—is very exciting." In a note to investors, Tim Anderson of Bernstein Research described the solanezumab "controversy" as one related to Lilly's "out of favor stock among the majority of sell-side analysts," in that "bears will likely continue to find reasons to be bears, and bulls will likely continue to remain bulls until more definitive data on solanezumab is generated."

Anderson, as of late October, put solanezumab's chances of eventual approval at about 40 percent. Seamus Fernandez, of Leerink Swann, gave solanezumab a 30 percent to 50 percent chance of earning $5 billion in sales in 2022, "despite evidence giving a modest signal of cognitive benefit at 18 months."

"Alzheimer's disease affects the most complicated functions of the most complex organ in the body," said William Thies, chief medical and scientific officer at the Alzheimer's Association. The consensus of the research community is to temper expectations and keep pushing for increases in government funding for early stage research. Combating Alzheimer's disease will require a multilateral approach across many fields of science: "activity must span the range of tangled plaques, beta amyloid, tau," you name it, says Les Funtleyder, president of the investment advisory division at Poliwogg. " The problem is that we know little of the etiology of the disease, so finding a new drug is particularly hard when you can't even necessarily identify the disease in vivo."

Les Funtleyder
Even so, industry, government and academia are racing ahead. In October, Washington University School of Medicine in St. Louis announced worldwide Alzheimer's prevention trials to commence in early 2013, conducted by the Dominantly Inherited Alzheimer's Network (DIAN) Trial Unit, and supported by the National Institutes of Health (NIH), the Alzheimer's Association, and the DIAN Pharma Consortium, a group of 10 pharmaceutical companies serving as trial advisors. So far, the trials will include Lilly's solanezumab, Roche's gantenerumab, and a small molecule beta-secretase (BACE) inhibitor currently in Phase II, also from Lilly. It goes without saying that any safe and truly disease-modifying drug to reach the market in the next five to 10 years will be handsomely rewarded by payers.

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