NEWS OF THE W EEK
CLINICAL TRIAL FAILURES RESEARCH: Faltering drug candidates
have cost Pfizer, BMS, and others hundreds of millions of dollars
S
EVERAL BIG pharmaceutical firms have been hit
by clinical setbacks that are weakening their drug pipelines at a time when older products are falling to competition from generics (see page 22). Pfizer and its partners Johnson & Johnson and Elan have discontinued development of bapineuzumab, an antibody against amyloid-β, a protein that makes up the hallmark plaque in the brains of people with Alzheimer’s disease. Pfizer disclosed in July that the first of four Phase III clinical trials of bapineuzumab was not successful. That study tested the drug in people carrying the gene ApoE4, a population that had not seen an improvement in an earlier trial. Even so, researchers had hoped the treatment might prove effective for noncarriers of the gene. But last week Pfizer halted studies to test the drug among
AIRBORNE SULFUR DIOXIDE OXIDANT IDENTIFIED
An air-sampling tower sits in the forest at the Station for Measuring Forest EcosystemAtmosphere Relations II in Finland, where the research took place.
ATMOSPHERIC CHEMISTRY: Emissions
JUHO AALTO/U OF HELSINKI
from trees are key to new pathway
A
NEWLY IDENTIFIED atmospheric chemistry
pathway for turning sulfur dioxide into sulfuric acid links pollution, natural ecosystems, air quality, and climate (Nature, DOI: 10.1038/nature11278). Sulfur dioxide is a common atmospheric pollutant emitted by both volcanos and industrial processes, such as the burning of sulfur-containing coal or oil. In the atmosphere, SO2 is oxidized to sulfuric acid, which in turn seeds aerosol particles. Near Earth’s surface, aerosols harm air quality; higher up, they may seed clouds and reflect or absorb sunlight. Researchers have long believed that SO2 oxidation proceeded primarily through hydroxyl radical chemistry, but the amount of sulfuric acid produced in the atmosphere was greater than what hydroxyl radicals could produce. In the new study, R. Lee Mauldin III of the University of Helsinki, in Finland, and the University of Colorado, Boulder, and coworkers suggest that WWW.CEN-ONLIN E .ORG
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noncarriers after the first Phase III trial also failed. Bapineuzumab came out of a long-standing collaboration between Elan and Wyeth, which Pfizer acquired in 2009. That same year, J&J paid $500 million to buy into Elan’s share of the partnership. Bapineuzumab marks the second high-profile Alzheimer’s drug failure for Pfizer. In 2008, the firm paid Medivation $225 million for access to dimebon, a small molecule that tanked in Phase III studies in 2010. The bapineuzumab failure is also problematic for Elan because it now depends largely on the multiple sclerosis drugs Tysabri and BG-12, which is on the brink of commercialization. Shares of Elan fell 15% after the poor data from the first Phase III study came out, making Elan a potential acquisition target by its multiple sclerosis drug partner Biogen Idec, according to Leerink Swann stock analyst Marko Kozul. Meanwhile, Bristol-Myers Squibb has experienced its own late-stage disappointment. Earlier this month, the company abruptly halted a Phase II study of BMS-986094, an NS5b inhibitor to treat hepatitis C, after a patient experienced a serious heart-related side effect. BMS had just added the drug candidate to its pipeline in January, when it paid $2.5 billion to buy Inhibitex. Analysts say the drug, a key component of BMS’s latestage pipeline, will be delayed and possibly scrapped entirely. Either way, BMS will fall behind competitors developing all-oral regimens for hepatitis C.—LISA JARVIS
carbonyl oxides formed from plant-emitted alkenes can also oxidize SO2. Incorporating this additional chemical pathway for sulfuric acid formation will help reduce uncertainties in climate models, writes Dwayne Heard of the University of Leeds, in England, in a commentary accompanying the new report.“In calculations predicting regional and global temperature rises caused by human activities, the largest uncertainties are associated with aerosols and clouds,” he writes. Mauldin’s team observed SO2 oxidation in a forest in Finland even during the evening and night, when hydroxyl radical chemistry doesn’t happen. They also observed SO2 oxidation when they removed hydroxyl radicals from daytime samples. Additional laboratory work showed that SO2 could be oxidized in the presence of ozone and alkenes—and when the researchers placed freshly cut spruce and pine branches near the inlet of their mass spectrometer. Mauldin and colleagues propose that, in addition to the hydroxyl radical pathway, SO2 gets oxidized by Criegee intermediates. Criegee intermediates are carbonyl oxides with some biradical and some zwitterionic character. They form in the atmosphere when ozone reacts with plant-emitted alkenes, such as limonene and α-pinene. Research published earlier this year demonstrated that the simplest Criegee intermediate, CH2OO, reacts quickly with sulfur dioxide to form sulfuric acid (C&EN, Jan. 16, page 10).—JYLLIAN KEMSLEY
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