NEWS OF THE WEEK
MYLOTARG MUST GO REGULATORY ACTION: The only antibody-drug conjugate on the market has efficacy and safety issues
P
FIZER HAS AGREED to stop selling the cancer
drug Mylotarg, an antibody-drug conjugate (ADC) that has been on the market since 2000. FDA made the request after recent clinical studies failed to show any benefit from the drug and actually found that more patients taking it died than those who were receiving Linker Toxin chemotherapy alone. Fewer than 2,500 n Antibody patients in the U.S. receive Mylotarg annually, Pfizer says. CONJUGATE Mylotarg Because Mylotarg was thought to consists of an anti-CD33 IgG4 address an unmet medical need, it was κ antibody linked to a bacterial approved on the basis of limited data calicheamicin toxin. under an accelerated process—but only to treat patients who are age 60 and older with relapsed acute myeloid leukemia. Under the process, Wyeth, which Pfizer acquired last year, was required to conduct postapproval studies to show the drug’s benefit. Mylotarg is the first, and to date the only, ADC to
BATTERY BEGINNINGS BREAKING GROUND: Dow venture starts
work on lithium-ion battery plant
V
ICE PRESIDENT Joseph Biden visited Midland,
Mich., last week to help break ground on a new Dow Kokam lithium-ion battery plant. Half the cost of the facility’s first phase will be paid for with a $161 million Department of Energy grant, which is part of the funds from the American Recovery & Reinvestment Act of 2009. Construction of the facility actually began last month, so the dignitaries on hand—including Biden, Dow Chemical CEO Andrew N. Liveris, Michigan Gov. Jennifer Granholm, and Dow Kokam CEO Ravi Shanker—held a mock groundbreaking ceremony by lighting up signs shaped like lightning bolts. In his remarks, Biden characterized the federal government’s investment in the facility as “seed money.” He said that DOE is workDOW
Vice President Biden greets construction workers at the ground-breaking ceremony for Dow Kokam’s advanced battery facility in Midland, Mich.
WWW.CEN-ONLINE.ORG
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reach the market. It consists of a monoclonal antibody— targeting CD33-positive cancer cells—coupled by a chemically labile linker to a highly potent cytotoxic agent. Intended to be potent yet selective, ADCs are long-sought-after “magic bullets” in drug development, says Enrico T. Polastro, a Brussels-based senior industry specialist at the consulting firm Arthur D. Little. Mylotarg, however, has had limited commercial success. Beyond the restricted patient population, another drawback is its small therapeutic window, or the narrow range between an effective and an adverse dose. The drug is linked to potentially fatal liver toxicity; the occurrence of this condition has increased with the drug’s use. The drug’s weakness is likely due to the chemical linker, which relies on a pH-dependent release mechanism and might not be sufficiently stable, according to a recent review article by researchers at the Swiss life sciences firm Lonza (Bioconjugate Chem. 2010, 21, 5). If this is the case, too much cytotoxin can be released in the bloodstream instead of being delivered to the target. To overcome such problems and advance new ADC candidates through clinical trials, several drug companies are trying to develop improved linkers (C&EN, Dec. 14, 2009, page 26). Although researchers continue to design and synthesize ADCs, they have yet to prove that they can overcome the practical difficulties, Polastro says. Seeing the only approved product withdrawn “won’t reassure people,” he adds.—ANN THAYER
ing to “dramatically change the way we produce and use energy” and that the Dow Kokam plant is part of an effort to “launch entirely new industries and create jobs in a virtuous cycle of innovation.” The plant will manufacture prismatic lithium-ion battery cells and packs mainly for the transportation industry, with secondary uses in utility storage and defense. The facility’s first phase, set to open in 2012, will have an annual capacity of 600 million watt-hours— equivalent to the battery power needed to run 30,000 all-electric vehicles—and will employ 320 workers. Dow Kokam was established in 2009 as a partnership between Dow; TK Advanced Battery, which owns a stake in the battery maker Kokam; and the French firm Dassault, which makes electric-vehicle power systems. In addition to the federal funds, Dow Kokam received $180 million in tax incentives from the state of Michigan. “The government seed money helped us catalyze this effort,” Ravi Ramanathan, vice president of business development at Dow Kokam, tells C&EN. “This is a very capital-intensive industry. When we talk about making batteries, it’s not for the faint of heart.” In addition to capital concerns, Dow Kokam and other battery manufacturers might find a dearth of customers for their products, warns Jacob E. Grose, a senior analyst at Lux Research. “Our best estimates for electric-vehicle sales—unless gas prices unexpectedly spike—show that they won’t scale up at the rate needed to use all these batteries,” he says.—MELODY VOITH
JUNE 28, 2010
