Natalie Taylor, Ph.D.
Mylan announced yesterday that the company has launched the first generic version of escitalopram (Forest Laboratories’ Lexapro, Lundbeck’s Cipralex/Seroplex). Under an agreement with Forest, Mylan will exclusively be able to market its product until the pediatric exclusivity of Lexapro’s patent expires in mid-March 2012. The launch of generic escitalopram marks the end of an era for branded selective serotonin reuptake inhibitor (SSRI) antidepressants.
The FDA’s approval of Eli Lilly’s Prozac (fluoxetine), the first SSRI to reach the U.S. market, sparked a complete overhaul of the way that major depressive disorder (MDD) was treated. Up until Prozac became available in early 1988, MDD was managed primarily with tricyclic antidepressants and monoamine oxidase inhibitors—drugs that carried a myriad of significant and life-threatening side effects, not to mention the potential for causing fatal dietary and drug interactions. Due to its superior safety and tolerability over older antidepressants, Prozac rapidly became the preferred first-line antidepressant for MDD, earning an impressive $350 million in the United States within its first year on the market. It was quickly followed by four “me-too” SSRIs: sertraline [Pfizer’s Zoloft/Lustral/Besitran], paroxetine [GlaxoSmithKline’s Paxil/Seroxat], citalopram [Forest Laboratories’ Celexa, Lundbeck’s Cipramil/Seropram], and finally escitalopram--the last SSRI to reach the U.S. market in 2002.
Forest Laboratories and Lundbeck at once were faced with the significant challenge of promoting Lexapro in a market that was nearly saturated with well-established SSRIs. Additionally, escitalopram was the (S)-enantiomer of citalopram, leading to speculation that the product was merely a marketing ploy by the companies and carried no significant clinical benefits over the racemic version of the drug. However, Forest and Lundbeck were able to overcome these sentiments by conducting and publishing a multitude of post-marketing clinical trials of escitalopram in MDD and other psychiatric indications. When marketing the drug to physicians, Forest and Lundbeck highlighted in vivo data, secondary data points, and post-hoc analyses from human and animal studies comparing escitalopram to citalopram, sertraline, venlafaxine, and paroxetine. By doing so, the company effectively communicated to physicians that escitalopram was safer, more tolerable, more selective for the serotonin transporter, and even could offer superior efficacy over its competitors—despite escitalopram’s close similarities to other SSRIs. These fierce promotional efforts, combined with the gradual loss of market exclusivity of the other SSRIs, led escitalopram to become the highest-selling product for the treatment of unipolar depression (i.e., MDD, minor depression, and dysthymia). In 2010, we estimate the product garnered $2.1 billion in the seven major pharmaceutical markets, representing almost 18% of sales alone in the $11.6 billion unipolar depression market.
Generic versions of escitalopram will substantially boost revenue for Mylan, Teva, and other generic drug manufacturers. Teva had previously attempted to launch its generic version of Lexapro in 2006, when it challenged the validity of Forest’s patent for the product in a paragraph IV filing. However, the U.S. District Court of the District of Delaware, and later, the Court of Appeals for the Federal Circuit ruled in favor of Forest, putting a halt to Teva’s ambitions.
It is unlikely that the peak-year sales of more recently launched antidepressants in the United States, such as Pfizer’s Pristiq (desvenlafaxine) and Forest’s Viibryd (vilazodone), will ever approach those of escitalopram. And given the developmental pipeline for unipolar depression disorders, it is even more unlikely that any emerging therapy will dislodge the now-genericized SSRIs as first-line treatment choices for MDD during the next decade. Decision Resources forecasts that by 2015, the sales of Forest and Lundbeck’s branded escitalopram for the treatment of unipolar depression will fall to $329 million. Indeed, the arrival of generic escitalopram marks the end of an important era in psychopharmacology—one which ultimately revolutionized the treatment of MDD.