Once again, a tiny open-label study using the potent anesthetic ketamine has kicked up stellar data for combating depression, grabbing headlines in some prominent publications. But this time a small, largely unknown private biotech company has seized on the study to tout its potential for gaining an FDA approval for a unique combination of drugs aimed at achieving a quick yet durable response for bipolar patients.
Ketamine, better known as Special K when it's abused on the party scene, has been a popular drug for academic groups looking for a quick-hit study. A series of small human studies has shown that the drug delivers an almost immediate benefit for large percentages of severely depressed and often suicidal patients. The drug, though, is also associated with severe side effects, including hallucinations, and has an ephemeral effect. As a result, Johnson & Johnson ($JNJ), AstraZeneca ($AZN) and others have tried, and often failed, at coming up with revised versions of this drug or related therapeutics that could be used to safely control depression over a prolonged period.
The latest study involving ketamine comes out of Columbia University. Three investigators at the university ran a study with 8 patients and concluded that a combination of drugs including ketamine triggered a 50% reduction in depression and a 75% reduction in suicidality, or suicidal thinking, among patients who were not responding to standard meds. That's not unusual. What's different about this study, though, is that the investigators added D-cycloserine, a TB drug which also targets the NMDA receptor that has become an alluring target in depression, a pervasive disease that has frustrated many developers and driven many of the largest players--like AstraZeneca--out of the field.
The placebo effect has often run out of control in studies in recent years, swamping any response to the drug being studied.
Four of the patients in the study were also taking Lurasidone, an antipsychotic that is sometimes used to treat bipolar depression. NeuroRx, which did not fund the Columbia study, is developing a combination of Lurasidone and D-cycloserine as Cyclurad, with a plan to match it with ketamine to get the durable response that investigators have been seeking for years.
The company is touting this data as "the first clinical report showing that the ketamine effect can potentially be sustained for two months with additional agents."
The CEO of NeuroRx is Jonathan Javitt, described in his LinkedIn profile as a senior fellow at the Potomac Institute for Policy Studies who's been focused on information tech and health economic. In the press release today, the company also adds that he was "instrumental in developing high-impact drugs for Merck, Pfizer, Pharmacia, and Allergan."
"These first-in-man data are very encouraging. If these findings can be confirmed in a larger scale study, Cyclurad could, if approved by FDA, potentially achieve important benefits for people with bipolar depression and suicidality," said Chaim Hurvitz, a founding investor and director of NeuroRx, in a statement.
Columbia's Joshua Kantrowitz was much more restrained. "This was some pilot data suggesting that D-cycloserine may be a compound that can prolong the ketamine effect," he told USA Today. "I wouldn't argue for people to run out and put everybody on this drug yet. I would argue for doing a future study."
USA Today also notes that some three million Americans suffer from bipolar depression, a notoriously difficult disease to treat. Against that patient population, 8 patients would be considered small even for a pilot study. But anything related to ketamine gets a swift and immediate response in the media, making it possible for a tiny biotech like NeuroRx to find itself in the spotlight without any data of its own to back up its business plan.
Javitt wasn't pleased with FierceBiotech's story and headline. "I'm not sure where the 'big boast' was in the press release," he noted in an e-mail Wednesday night. But he's also not backing away from his belief that the data are significant. "There's no question that 8 patients is a small study and that an open-label study is never definitive. However, there's also no question that a statistically-significant effect size was seen."
The company certainly isn't the only outfit testing an NMDA approach to depression. Naurex, working with an $80 million round, has garnered positive data for its NMDA modulators. J&J is still at work on its own revised version of ketamine, an intranasal drug called esketamine. Cerecor, which attracted some A-list venture backers, has a midstage program underway for its NMDA drug, CERC-301, which failed last spring in a Phase II study with 135 patients. The company plans to further study the drug at a higher dose.
AstraZeneca had a version of ketamine--AZD6765--in Phase II but quickly and quietly killed the project after it failed the second of two midstage studies. At the time, AstraZeneca offered no detailed explanation of the data or what went wrong with the program. The news about the failure also attracted none of the big media coverage associated with success--even with the thinnest of possible data sets.