Lamivudine - History

History

Racemic BCH-189 (the minus form is known as Lamivudine) was invented by Dr. Bernard Belleau while at work at McGill University and Dr Paul Nguyen-Ba at the Montreal-based IAF BioChem International, Inc. laboratories in 1988 and the minus enantiomer isolated in 1989. Dr. Yung-Chi Cheng of Yale University in collaboration with R.F. Schinazi and D.C. Liotta first reported the anti-hepatitis B virus (HBV) activity of Lamivudine in cell culture which eventually led to the first oral antiviral agent for the treatment of HBV. Subsequently the group at Emory University headed by Dr. Dennis C. Liotta and Dr. Raymond F. Schinazi developed a synthesis for the BCH-189 that gave exclusively the beta-enantiomers. They then went on to resolve the two enantiomers and demonstrated that the antiviral activity at non-toxic concentrations resided in the (-)-enantiomer, now called Lamivudine. The Emory patents to lamivudine were later invalidated by the original inventors. The drug's effectiveness for treating HIV in combination with AZT was discovered accidentally when a patient took Zidovudine secretly while in a clinical trial of Lamivudine monotherapy. The drug was later licensed to the British pharmaceutical company Glaxo by Biochem Pharma (now Shire Pharmaceuticals) for a 14 percent royalty. GlaxoSmithKline subsequently ceded the product to its ViiV Healthcare joint venture in 2009.

Lamivudine was approved by the Food and Drug Administration (FDA) on November 17, 1995 for use with zidovudine (AZT) and again in 2002 as a once-a-day dosed medication. The fifth antiretroviral drug on the market, it was the last NRTI for three years while the approval process switched to protease inhibitors. According to the manufacturer's 2004 annual report, its patent will expire in the United States in 2010 and in Europe in 2011.