Decision Resources predicts that the two greatest beneficiaries of this shift will be GlaxoSmithKline and Merck & Co, both of which are currently in the lead amongst companies trying to bring triple reuptake inhibitors to market.
No currently marketed antidepressant inhibits the reuptake of all three neurotransmitters linked to depression: serotonin, norepinephrine, and dopamine. But preclinical studies and clinical trials indicate that a drug inhibiting reuptake of all three of these neurotransmitters could produce more rapid onset of action and greater efficacy than traditional antidepressants.
GSK's lead candidate in this class - NS-2359 - will be the first triple reuptake inhibitor to market, launching in 2009 and growing steadily in the following five years, according to Decision Resources. Meanwhile, it predicts that Merck's triple reuptake inhibitor - DOV- 216303 - will enter the market in 2011. Both compounds will reach approximately $4 billion in sales in 2014.
In addition to their clinical profiles, the triple reuptake inhibitors could also benefit from the safety concerns that have plagued existing antidepressant classes, and particularly the selective serotonin reuptake inhibitors.
The SSRI class of drugs, which includes GSK's Paxil/Seroxat (paroxetine), Eli Lilly's Prozac (fluoxetine) and Pfizer's Zoloft (sertraline), already carries a "black box" warning highlighting an increased risk of suicidal behaviour amongst children and adolescents. Moreover, the class has some serious drawbacks, including a two to six week lag before they start to work, a low rate of response and a low rate of remission. If triple reuptake inhibitors can demonstrate a more rapid onset, higher efficacy and fewer side effects, their commercial success will be assured.
Decision Resources' study, entitled The Antidepressant Market Through 2014: Focus on Emerging Therapies and New Indications, also suggests that cost-saving policies set by third-party payers will constrain the antidepressant market, especially for emerging agents with little to differentiate themselves.
"Only antidepressants with novel mechanisms of action, and presumably those labeled for treatment of a novel indication, will be able to compete within the growing selection of antidepressants," said Anathea Waitekus, analyst at Decision Resources. "These drugs will have the greatest chance of earning favourable pricing and reimbursement status, as well as formulary inclusion."
DOV Pharmaceuticals, which licensed its lead triple reuptake inhibitor to Merck in a deal valued at up to $455m, in March started Phase I trials of another candidate, DOV 102,677. Merck has right of first refusal on these follow-up compounds.