By Kirell Lakhman

Sanofi-Aventis' weight loss drug Acomplia was taken off the market in Europe in 2008 because its developers failed to consider that certain genotypes would cause some patients taking the drug to become depressed and lead five of them to commit suicide.

Here's an unsolicited piece of advice for the French pharma and every clinical lab that dabbles in developing companion diagnostics: Use this failure as a spur to forge collaborations to create a companion diagnostic that could identify patients for whom Acomplia would be a safe bet.

A research team led by Eric Topol of Scripps Translational Science Institute last week wrote a mea culpa of sorts — but not necessarily about themselves — concluding that genetic testing might have been able to identify those people and spare an otherwise safe and efficacious drug.

The failure of Acomplia needn't be a fait accompli.

Topol's paper, which appeared online in The Lancet last week, sought to assess whether the drug, generically known as rimonabant, "would improve major vascular event-free survival."

Acomplia blocks the endocannabinoid receptor — marijuana users will be familiar with it — which reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose.

Five people in the Topol's study of more than 18,000 individuals committed suicide. Four were taking the drug; one was in the placebo arm.

"Finding the gene for severe adverse drug reactions is a lot easier than we ever thought it would be," Topol told Reuters after the study appeared. "We probably could have figured out genomically who was susceptible and that drug could be quite viable."

As the news service rightly notes, there exists still the opportunity to "rescue the once-promising treatment," even though Topol later says "it is likely too late to revive" it.

This is where clinical labs — and their ability to kick-start drug-diagnostic collaborations — can come in. And I'm not only referring to the resource-rich reference labs that operate vast clinical trial arms, among them Quest and LabCorp.

In fact, there's already some evidence that supports the theory that at least one genetic polymorphism could contribute to depression and suicidal thoughts in certain people.

It's certainly worth more than a sophomore try, not least because Acomplia has been shown to help people lose weight, regain normal blood sugar levels, and improve serum triglyceride and HDL levels.

"Genomics could potentially be used to pre-empt use of the drug in individuals with risk of serious adverse events," Topol said in a statement. In The Lancet study itself, the authors note that "[e]ndocannabinoid blockade could have proven viable, if a genome-wide association study had been done to establish what sequence variants are linked with suicides, suicide attempts, or significant neuropsychiatric side-effects."

Describing the study, the authors added that "knowledge about the appropriate clinical criteria for inclusion, with use of genomic data indicating high risk of side-effects at the time of study entry, could have pre-empted or at least reduced the serious psychiatric side-effects."

For example, a study published in the April issue of the Archives of General Psychiatry, referenced in The Lancet paper, "showed that single nucleotide variants in [the] tyrosine kinase receptor gene NTRK2 involved in neurotrophic signaling were associated with more than four-fold increased risk of suicide.

A scan of a dozen clinical labs chosen at random did not turn up a test for this gene or any of its alleles.

But this observation wouldn't have stopped Topol's team, and that is to its benefit. "[T]he clinical benefit of endocannabinoid-1 blockade could have been manifest in patients with a particular gene variant in the endocannabinoid-1 or related pathways," The Lancet paper notes.

As the researchers conclude in their study, "[w]ith such an important cluster of diseases of obesity, metabolic syndrome, and diabetes, innovative approaches are urgently needed." And with them useful clinical diagnostics that could help identify patients who can safely take the drug.

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