Patent Expirations Could Mean Biologics Competition
As patent expirations creep closer, blockbuster drugs face increasing competition, and the FDA faces increasing pressure.
Mr. Lamb is a freelance pharmacy writer living in Virginia Beach, Virginia, and president of Thorough Cursor Inc.
A central theme of PharmacyTimes' annual updates onpending drug patent expirationsand equivalent generic launcheshas been that subjecting blockbusterdrugs to competition from unbrandedproducts is increasingly and dramaticallyreshaping the US medication marketplace.1,2 This trend is expected tocontinue for traditional, small-moleculedrugs.
If recent discussions among federallegislators, the FDA, and drug manufacturersproduce tangible results, seismicshifts in the biopharmaceuticalsector of the drug market also willappear on the horizon. Bills allowingthe FDA to develop mechanisms forreviewing and approving applicationsfor follow-on biologics made progressin Congress in 2007.
Drug-agency officials approachedmembers of business committees fromthe Senate and House of Representativesin early February to ask for aseat at the table if new legislationregarding the regulation of therapeuticallyand structurally similar biologicsis introduced. Companies that makebiopharmaceuticals are not opposed togeneric biologics in principle; rather,they want to make sure that their originalpatented products are guaranteedadequate periods of market exclusivity.
Developments Among Traditional Drugs
When Pfizer's patent on Norvasc(amlodipine besylate) expired on thelast day of January 2007, a genericequivalent produced by Apotex immediatelywent on sale. More than adozen FDA-approved, unbranded versionsof the calcium channel blockerthat had once been the most-prescribed,best-selling antihypertensivein the United States are now available.Although Norvasc generated >$2.7 billionin sales for Pfizer with 40 millionprescriptions in 2006, the companyestimated last spring that sales wouldbe half of that in 2007.2,3
Similar dramatic losses of marketshare are likely to be reported for anumber of blockbuster drugs that lostpatent protection in 2007, includingAmbien (zolpidem, sanofi-aventis),Coreg (carvedilol, GlaxoSmithKline),and Zyrtec (cetirizine, Pfizer). Table 1shows that GlaxoSmithKline's Advair(fluticasone and salmeterol) andAvandia (rosiglitazone) are just 2 of theother top-grossing medications thatwill go off patent within the next 20months.
Follow-on Biologics More Likely Than Ever
Currently, no generic biologics existin the United States. Efforts to changethat picked up steam last year whenRep Henry Waxman (D, CA) introducedHR 1038, the Access to Life-Saving MedicineAct, which would have requiredthe FDA to create ways to license biologicsthat are very similar, if not identical,to existing licensed products.6 TheSenate version of the bill, S1695, was reported out bythe Health, Education, Labor,and Pensions Committee butnot acted on by the fullchamber.7
Key sticking points for thelegislation were the FDA'sapparent unwillingness toaggressively pursue the authority tovet generic biologics and industrydemands that patent terms for innovatorbiologics run 14 years instead ofthe bill's proposed terms of 12 years.Regulators, at least, now appear to bemore receptive.
CongressDaily reported in the firstweek of February that FDA officials haddiscussed developing a legislativeframework for follow-on biologics withsenior members of the House Committeeon Energy and Commerce andthe Senate Finance Committee.8 Thatframework, according to an FDA official,would "include necessary provisionsto ensure the safety and effectivenessof these biologic products forpatients ... [and] adequate intellectualproperty protections to preserve continuedrobust research into new andinnovative lifesaving medications."9
The agency is downplaying expectationsfor the initial discussions. During aquestion-and-answer session followinghis testimony on President Bush's budgetproposal for Fiscal Year 2009,Michael Leavitt, secretary of the Departmentof Health and Human Services,told the Senate Finance Committeethat "biologics are an importantmedical development. We'd like to seethem expanded in their generic form.We're anxious to see abipartisan proposal."10
Biopharmaceuticals setto go off patent within thenext 3 years are listed inTable 2. Genotropin (somatropin,Pfizer), NovoSeven(coagulation factor VIIa,Novo Nordisk), and Humira(adalimumab, Abbott) were among thetop 200 best-selling prescriptions in2006. With no timeline announced foraction on expanding FDA's authority tolicense generic versions, however, itremains unclear when these productscan expect to face low-cost competitors.
- Faden, M. Patent expirations produce top-selling generic drugs. Pharmacy Times. August 2006. www.pharmacytimes.com/issues/articles/2006-08_3757.asp. Accessed February 7, 2008.
- Lamb E. Top 200 prescription drugs of 2006. Pharmacy Times. November 2007. www.pharmacytimes.com/issues/articles/2007-05_4629.asp. Accessed February 7, 2008.
- Pfizer Lowers 2007 Outlook on Norvasc. International Business Times. April 20, 2007. www.ibtimes.com/articles/20070420/pfizer-outlook.htm. Accessed February 7, 2008.
- FDA Web site. Electronic Orange Book. www.fda.gov/cder/ob. Accessed February 7, 2008.
- Drugs@FDA Web site. www.accessdata.fda.gov/scripts/cder/drugsatfda. Accessed February 7, 2008.
- Detailed Outline: The Access to Life-Saving Medicine Act. February 14, 2007. Representative Henry Waxman Web site. www.henrywaxman.house.gov/pdfs/biologicsbillsummary_2.14.07.pdf. Accessed April 5, 2007.
- Martino M. Senate HELP Committee passes bill to allow FDA approval of generic versions of biotechnology medications. Fierce Biotech. July 2, 2007. www.fiercebiotech.com/node/7470. Accessed February 7, 2008.
- Johnson F, Edney A. CongressDaily. http://nationaljournal.com/about/congressdaily. Accesssed February 6, 2008.
- Edney, A. CongressDaily. nationaljournal.com/about/congressdaily. Accessed February 5, 2008.
- Hearings Before the Senate Committee on Finance, 110th Congress, 2nd Sess (2008) (testimony of Michael O. Leavitt, secretary, Department of Health and Human Services).