The business strategies of companies involved in chiral drug development were cast into doubt in October after Eli Lilly (Indianapolis, IL) decided not to pursue the development of R-fluoxetine, Sepracor's (Marlborough, MA) single isomer form of the anti-depressant Prozac. $3.9 billion was wiped off Sepracor's market capitalization as investors called into question the entire utility of single enantiomers as a means of improving drugs and managing product life cycles. However, most analysts say the case is insignificant and cannot be extrapolated to Sepracor's pipeline or those of similar companies.
The business of developing single isomer drugs came about because the chemical production methods used for pharmaceuticals often produced racemic mixtures of two enantiomers. In the case of thalidomide, it was shown that one enantiomer was responsible for efficacy and another for side effects. Companies like Chiroscience (Slough, UK) and Sepracor based businesses on developing single enantiomer versions of old drugs in the hope of improving their pharmakogenetic profile—increasing efficacy and reducing side effects. Because regulatory authorities accept relevant data from clinical trials of racemates, developing chirally pure versions was thought to be a short cut to market—quicker, cheaper, and less risky than other endeavors. Successful examples include Chiroscience's anesthetic levobupivacaine (chirocaine), the single isomer version of Astra's bupivacaine (marcane); it retained all the activity of the racemate but with less cardiotoxicity, thus expanding utility to childbirth, which was contraindicated for Astra's version.
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