Thursday, January 15, 2009

Schering's Asenapine -- Even If Approved -- Faces A "Cloudy Commercial Prognosis"

With all the news generated recently about the obesity risks (which may lead to elevated cardio-vascular risks) from Risperdal, Abilify and Zyprexa, et al. -- given the very common long-term use of these sorts of anti-psychotic drugs -- I thought it worthwhile to highlight the view of many analysts, on Asenapine (to be tradenamed "Saphris"), per a Forbes article, out this morning.

Note that this does not bode well for moving the drug over to treating Alzheimers-related dementia:

. . . ."Even if approval occurs, the commercial outlook for Saphris seems challenging," wrote Sanford Berstein analyst Tim Anderson in a note to investors. "The drug would be entering a crowded atypical antipsychotic category where a benchmark product -- Johnson & Johnson's Risperal -- recently went generic, and Schering has no commercial presence in this area, meaning it would need to build infrastructure to market Saphris." Anderson added that his expectations for the drug's approval had been low until this point. . . .

Good luck with that, Dr. Koestler.

1 comment:

Anonymous said...


I took a look at the NEJM article and editorial on cardiovascular toxicity. It only deals with sudden death and claims it's roughly correlated with QT prolongation. This is very different from long term cardiovascular toxicity and doesn't include cardiopulmonary toxicity, which the editorial clearly points out e.g. CHF. Nor does it address total cause mortality, e.g. stroke and so on. So it clearly implies that there may be other types of cardiovascular and cardiopulmonary toxicities with antipsychotics (which may not be secondary to metabolic effects such as weight gain and diabetes as occur with Zyprexa).

The editorial also makes the point that the risk from these other chronic toxicities may be different and thus use in children and the elderly should be avoided.

For Zyprexa it's clear from the summary basis of approval that it was not approved for use in psychosis in the elderly in 1996 due to a higher risk of these other cardiovascular toxicities in this population. Yet Lilly went ahead and promoted it off-label anyway and just a few days ago plead guilty to doing so. Now this past week FDA just gave the green light for off-label promotion.

For a scientist if you want to know what to look for in a drug a priori you need to look at what is already known about similar compounds and especially structurally similar ones. I believe I have previously discussed Zyprexa on Pharmalot and that it appears to cause a phen-fen like toxicity.

Even if these other toxicities are qualitatively similar the question then becomes are they quantitatively similar to similar products. One way you can evaluate this is by comparing the incidence of cardiopulmonary toxicities with the control drug in the controlled studies, especially if it is a structurally similar. This is especially useful as it can be done prior to marketing rather than waiting for postmarketing surveillance and as you can compare similar populations using equivalent doses for similar timeframes and have good reporting. Thus if you had a much, much higher incidence of cardiopulmonary toxicities in the regular adult population then it would give you an indication of what you might expect under conditions of actual use. You could then even compare the incidence of events to the rates from historical data for the control drug in special populations such as the elderly. Doing this is wouldn’t even necessarily be that difficult, for if the rates were significantly higher you could get a quick read in a few minutes by just looking at summary data.