West Coast Editor
Vanda Pharmaceuticals Inc. followed up its Phase III success late last year with the schizophrenia tablet iloperidone by submitting a new drug application to the FDA. The company is using a personalized-medicine approach, partly to ensure the compound's efficacy and partly to quell any potential safety concerns - namely, problems with prolonged QT intervals, a common bugaboo in the class.
The company's stock (NASDAQ:VNDA) closed at $13.40, down 22 cents.
Prolonged QT interval (a wider stretch between the heartbeat's "Q" wave and its "T" wave) is "something the FDA thinks about quite seriously," noted Chip Clark, chief business officer for Rockville, Md.-based Vanda.
Iloperidone's QT prolongation, he said, is "within the boundaries of acceptability by the FDA, and we understand from physicians that it's not clinically relevant to them at these levels." Still, Vanda wanted to "add this layer of certainty of efficacy and/or safety," he said.
Rights to iloperidone, an atypical antipsychotic that binds to dopamine and serotonin receptors, came by way of a 2004 deal. Titan Pharmaceuticals Inc. had partnered the drug with Basel, Switzerland-based Novartis AG - where the core team at Vanda, founded in 2003, originated. Vanda's CEO Mihael Polymeropoulos founded and ran the pharmacogenetics group at Novartis for five years. (See BioWorld Today, June 10, 2004.)
"When Novartis had the compound, they made a business decision based on the QT prolongation to discontinue the program," Clark said. Before dropping iloperidone, though, the pharma giant had identified "a couple of genetic markers that pertain to [the drug's] metabolism and response," he said. "We've done additional work on this and prospectively confirmed a couple of these markers in the Phase III study that we ran."
By now, the much-tested compound has undergone 35 trials enrolling more than 3,000 patients. Data on markers are included with the study results in the NDA package.
"We haven't talked about what those genes are yet, only because we had been waiting for the right scientific forums, and we're getting our publications together," Clark said. Officials will be talking more about the discovered markers, and the ongoing search for more, at the American Society of Human Genetics annual meeting late next month in San Diego.
"Obviously, the FDA needs to approve the label and claims that may come around genetic markers," Clark said, adding that Vanda is exploring partnerships for the development of a genetic test that could be used with iloperidone.
"For our Phase III trial, we built, with a national lab, a simple blood test," he said. "That itself, or something very much like that, is what we would expect to commercialize."
Atypical, or second-generation, antipsychotics make up a mixed bag. "There are three or four chemical families that seem to hit those [dopamine and serotonin] receptors, and you have drugs with very different profiles, especially on the safety side," since the compounds bind to "a whole raft of other receptors" as well, Clark said.
Approved drugs in the class include New York-based Pfizer Inc.'s Geodon (ziprasidone) and Indianapolis-based Eli Lilly & Co.'s Zyprexa (olanzapine). Schizophrenia hits about 1 percent of Americans.
The need for a new therapy is strong, as shown by the oft-cited 1,493-patient Clinical Antipsychotic Trials of Intervention Effectiveness study, done by the National Institute of Mental Health and reported in The New England Journal of Medicine. Comparing four atypical antipsychotics head to head, the study found that 74 percent of patients quit their drugs after 18 months, either because the drugs weren't working or the side effects had become intolerable.
"We would by no means claim we have achieved the Holy Grail" of atypical antipsychotics with iloperidone and its biomarkers, Clark said, preferring to characterize Vanda's work so far as a "meaningful scientific contribution" to the field, with more possibly to come.
Also in its pipeline: VEC-162, in Phase III trials for sleep disorders, and VSF-173 for excessive sleepiness, in Phase II trials.