Fresh from the biologic pipeline


volume 27 number 3 mArCH 2009 nature biotechnology from Merck, of Whitehouse Station, N.J., which voluntarily pulled the drug from the market worldwide after data revealed an increased risk of heart attack and stroke in patients dosed for 18 months or more. “It wasn’t the start [of the safety crackdown], but it was the event that most normal Americans know about, because so many people know about Vioxx,” Egan says. “We thought [the pharmaceutical industry’s reputation] was bad when Vioxx was withdrawn, but we feel it’s worse now,” she adds, as public opinion regarding drug prices and profit margins continues to boil. The FDA’s continued recoil has been strong, and maybe too strong, in her view. A behindthe-scenes trend, she says, has FDA “more and more deciding not to approve something because they don’t think it’s needed—which is arguably illegal,” because the agency’s mandate is to determine whether the risk– benefit profile merits marketing clearance, rather than decide whether another drug works similarly on a given indication. “That’s happened a lot in the last year,” she says. “I think it’s going to get worse.” As an example from history that could repeat, Egan cites Arcoxia (etoricoxib), the secondgeneration COX-2 inhibitor from Merck. At an FDA advisory panel meeting several years ago, Arcoxia’s favorable risk-benefit profile “taken in isolation” was acknowledged, Egan notes, though the drug had a potential liver toxicity issue. Arcoxia failed to win approval mainly because New York–based Pfizer’s Celebrex (celecoxib) and other nonsteroidal anti-inflammatory drugs already served the ailments that Arcoxia would have targeted, she says, and Arcoxia was considered just one of a group of already available, effective medications rather than as one that should get separate consideration of benefits weighed against risk. A more recent example is Pfizer’s Fablyn (lasofoxifene), a selective estrogen-receptor another, and then figure out how they can be used to draw conclusions.” Kim Egan, an attorney with DLA Piper in Washington, DC, who often provides consultation for biotech and pharma firms facing potential FDA roadblocks, does not believe the REMS will fling open the window for drug approvals. In fact, she believes just the opposite. “It’s having a sort of backward effect,” she says. “REMS is simply making Congress more aware and more focused on FDA’s safety practices. In a sense, it’s attracting unwanted attention and causing [the agency] to be more cautious.” The REMS, which includes various provisions whereby safe use is assured and drug reactions are tracked, can be applied to compounds previously approved with the less-stringent risk minimization action plans (RiskMAPs). Among the higher-profile drugs cleared by the FDA with REMS attached in 2008 are Cimzia (certolizumab pegol), the PEGylated anti–tumor necrosis factor (TNF)-α antibody for adults with Crohn’s disease from Brusselsbased UCB; Entereg (alvimopan), the μ-opioidreceptor antagonist for postoperative ileus from Adolor, of Exton, Pa., and London-based GlaxoSmithKline (GSK); and Lexiscan (regadenoson), a stress agent for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress, from CV Therapeutics, of Palo Alto, Calif., and Deerfield, Ill.-based Astellas Pharma US. Egan feels the agency remains “gun shy” after the criticism it received after the high-profile withdrawal in 2004 of the cyclooxygenase-2 (COX-2) inhibitor Vioxx (rofecoxib) for pain Though still underfunded and low on staff, the US Food and Drug Administration (FDA) managed to approve 21 new molecular entities (NMEs) in 2008, picking up momentum in the second half of the year and breaking a slide in approvals that had continued since the turn of the present century—except for the ‘blip’ year 2004, when the agency’s Center for Drug Evaluation and Research gave its blessing to 36 products. Included in 2008 approvals for NMEs were five new biologics (Fig. 1, Table 1), a slight uptick from 2007’s 16 NMEs and two new biologics. In all, about 80 new drug applications and biologic license applications for medications won clearance in 2008, about the same as 2007, but most involved combo drugs, added dosing forms or new formulations of already approved compounds. The FDA is more focused on safety than ever, as Congress and the nervous public holds regulators and industry to harsh scrutiny. Sara Radcliffe, vice president of science and regulatory affairs for Washington, DC’s Biotechnology Industry Organization, cited “no huge, unwelcome surprises” in approvals. The Food and Drug Administration Amendments Act (FDAAA), signed into law in 2007, is “still shaking out.”

DOI: 10.1038/nbt0309-222

3 Figures and Tables

Cite this paper

@article{Osborne2009FreshFT, title={Fresh from the biologic pipeline}, author={Randall E. Osborne}, journal={Nature Biotechnology}, year={2009}, volume={27}, pages={222-225} }