(Updated, Sunday, December 8)
I highly recommend a terrific article by Ian Parker in this week's New Yorker about Merck's efforts to develop a novel insomnia drug, suvorexant. Normally I don't write about non-cardiology topics but I want here to call attention to one small, almost tangential detail buried in the middle of the story. It's not about the Merck drug but about another orexin antagonist from Actelion, almorexant:
"At the time, Jed Black, the Stanford sleep specialist, was on a two-year leave of absence, working full time on almorexant, the rival drug made by Actelion. Phase III trials of the drug were under way. This work has not been published, and Black cannot discuss it, although he recently described almorexant as having 'an absolutely remarkable profile' that was likely to outperform zolpidem in sleep maintenance. But, in early 2011, Actelion announced that it was halting the drug’s development, because of an undisclosed possible safety issue. Merck’s scientists speculated about the nature of the concerns, and feared for the future of suvorexant. Black said that the problem was 'straightforward,' but that Actelion had decided to pause and take its time. 'I don’t think almorexant needs re-tinkering at the molecular level,' he said, implying a problem of drug delivery. Black, who is back at Stanford, suspects that almorexant will be launched, and is certain that such drugs will eventually become dominant. (GlaxoSmithKline recently published results, from Phase II studies, of its own orexin antagonist.)"
The time frame is not entirely clear, but it appears that Actelion has been actively suppressing phase III data about almorexant for several years at least. The implication in the passage is that the the problem that surfaced with almorexant is not likely to be related to the class of the drug, but of course there's no way to know that for sure. Complete information should be available to other researchers and other companies developing drugs in this class. Most importantly, the company and the researchers who performed the trial are violating their obligation to the patients who volunteered to participate in this trial.
To be clear: confidentiality is essential while a trial is in progress. Once completed the full results should be presented and published as soon as is reasonably possible. There is no valid excuse to delay publication of phase III results based on commercial or marketing concerns. (For more on this important subject visit AllTrials.Net.)
I mentioned earlier that I don't usually write about non-cardiology topics. But there actually is one small aspect of this story that is related to cardiology. Earlier this year the American College of Cardiology announced the appointment of a new CEO, Shalom “Shal” Jacobovitz. In his previous job he was the president of the US division of Actelion.
For more on Actelion, see this blog post by Marilyn Mann.
Update: Following the publication of this blog I received several comments and tweets informing me that the results of the phase III almorexant trial had been published on ClinicalTrials.Gov (Click here for the ClinicalTrial.Gov page. Actelion has also published a trial summary on its website.) It seems likely that this is the phase III trial mentioned in the New Yorker trial, though it is impossible to fully verify this from the bare information in the article. But a cursory look at the ClinicalTrials.Gov page for this trial makes clear that the problems discussed above are still fully relevant.
On the ClinicalTrials.Gov site the study, called RESTORA 1, is described as a "Multi-center, Double-blind, Randomized, Placebo-controlled, Active Reference, Parallel-group Polysomnography Study to Assess the Efficacy and Safety of a 16-day Oral Administration of ACT-078573 in Adult Subjects With Chronic Primary Insomnia." There is no indication on the page why Actelion halted development of almorexant. We don't know what the problem is with this drug, and neither, presumably, do Merck, GSK, or other companies and researchers now testing other drugs in this class in people. It is entirely possible that people are now being harmed by a problem with this drug. We have no way of knowing at this point.
There are at least two additional major problems with this trial revealed on the ClinicalTrials.Gov site. Here is the tracking information as posted on ClinicalTrials.Gov:
So the trial started in March 2008 and was completed in September 2009, yet the final results were not submitted to ClinicalTrials.Gov until February 2013.
I am equally concerned by the "cone of silence" imposed on the trial investigators. There's an important disclosure about this on the ClinicalTrials.Gov page (click image to enlarge):
It's hard to know where to begin to respond to this. I guess the simplest approach is just to say that this sort of thing is completely unacceptable.
