Editing Telithromycin (section)

== History ==

French [[pharmaceutical company]] [[Hoechst Marion Roussel]] (later [[Sanofi-Aventis]]) began phase II/III [[clinical trial]]s of telithromycin (HMR-3647) in 1998. Telithromycin was approved by the [[European Commission]] in July 2001 and subsequently went on sale in October 2001. In the US, telithromycin received U.S. [[Food and Drug Administration]] (FDA) approval on April 1, 2004.

===Safety controversies and fraud===
FDA staffers publicly complained that safety problems and some data integrity issues were ignored prior to approval, and the House Committee on Energy and Commerce held hearings to examine these complaints. One doctor went to prison because she falsified data in her portion of the clinical trials (about 400 patients out of 24,000). Further, Ketek seemed to cause liver problems, including "liver failure", to a greater extent than would be expected of a common-use antibiotic.<ref>
{{cite journal | vauthors = Splete H, Wachter K | date = March 2006 | title = Liver toxicity reported with Ketek | journal = Internal Medicine News }}
</ref> The House Committee on Energy and Commerce held hearings.<ref>{{cite web |url=http://energycommerce.house.gov/cmte_mtgs/110-oi_hrg.021307.FDA_drug_supply.shtml |title=The House Committee on Energy and Commerce :: Hearing |access-date=2007-04-20 |url-status=dead |archive-url=https://web.archive.org/web/20070426053105/http://energycommerce.house.gov/cmte_mtgs/110-oi_hrg.021307.FDA_drug_supply.shtml |archive-date=2007-04-26 }} House of Representatives, The House Committee on Energy and Commerce, Honorable John D. Dingell, Chairman, Subcommittee on Oversight and Investigations, "The Adequacy of FDA Efforts to Assure the Safety of the Drug Supply", February 13, 2007.</ref>

Study 3014 was a key clinical trial of approximately 24,000 patients which Sanofi-Aventis submitted to the FDA to seek approval for Ketek. The doctor who treated the most patients in Study 3014 (about 400), Maria "Anne" Kirkman Campbell, served a 57-month sentence in federal prison after pleading guilty to mail fraud, by defrauding Aventis and others. The indictment states that Campbell fabricated data she sent to the company.<ref>{{cite web | url = https://www.fda.gov/foi/nidpoe/n41l.htm | archive-url = https://web.archive.org/web/20060930173220/http://www.fda.gov/foi/nidpoe/n41l.htm | url-status = dead | archive-date = September 30, 2006 | work = U.S. Food and Drug Administration | title = Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (Nidpoe) | vauthors = Ball L | date = 18 May 2006 }}</ref> Documents, including internal Sanofi-Aventis emails show that Aventis was worried about Campbell early in study 3014 but didn't tell the FDA until the agency's own inspectors discovered the problem independently.<ref>[https://www.wsj.com/articles/SB114644463095840108?mod=blogs] Infected Data: Fraud, Errors Taint Key Study Of Widely Used Sanofi Drug Despite Some Faked Results, FDA Approves Antibiotic; One Doctor's Cocaine Use; Company Defends Safety, By ANNA WILDE MATHEWS, Wall Street Journal,  May 1, 2006</ref>

In January 2006, an article<ref name="Clay KD 2006"/> in the March issue of ''Annals of Internal Medicine'' was published, citing three recent drug-induced liver injury cases likely due to telithromycin, one resulting in a liver transplant and one in death.

In July 2006, according to the ''New York Times'', unpublished e-mails from FDA safety official David Graham argued telithromycin had not been proven safe, that safer drugs were available for the same indications, and that the approval was a mistake and should be immediately withdrawn.<ref name="Harris, G">{{cite news| vauthors = Harris G | title=Approval of Antibiotic Worried Safety Officials | url=https://www.nytimes.com/2006/07/19/health/19fda.html | work=[[New York Times]] | date=2006-07-19 | access-date=2010-05-25}}</ref>

Between the start of telithromycin's marketing in mid-2004 and September 2006, there were 13 cases of liver failure, including at least four deaths, vision problems, blackouts, syncope, and potentially fatal cases of [[myasthenia gravis]]. ''The Times'' said that the FDA was embroiled in a "fierce battle" over the approval, fueled by exposure in the press.  Senator Charles E. Grassley (R-Iowa, chairman, Senate Finance Committee), Representatives Edward J. Markey (D-Mass) and Henry A. Waxman (D-Calif) held hearings.

===FDA Warning===
On February 12, 2007, after an advisory committee discussion and vote in December 2006, the FDA announced a revision to the labeling of Ketek. The changes included the removal of two of the three previously approved indications: acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis. The agency determined that the balance of benefits and risks no longer supported approval of the drug for these indications. Ketek remained on the market for the treatment of community acquired bacterial pneumonia of mild to moderate severity (acquired outside of hospitals or long-term care facilities). In addition, the FDA worked with the manufacturer to update the product labeling with a "[[black box warning]]," their strongest form of warning. Ketek's warning states that it should not be used in patients with [[myasthenia gravis]], a disease that causes muscle weakness.<ref>{{cite web |url=https://www.fda.gov/bbs/topics/NEWS/2007/NEW01561.html |url-status=dead |archive-url=https://web.archive.org/web/20070214112915/http://www.fda.gov/bbs/topics/NEWS/2007/NEW01561.html |archive-date=2007-02-14 |title=FDA Announces Label and Indication Changes for the Antibiotic Ketek|website=[[Food and Drug Administration]] }}</ref> Following this decision, Sanofi-Aventis withdrew the drug from active sales in the United States.