Allergan’s sizable Phase II study testing Botox as a treatment for major depression among women missed hitting statistical significance for the primary endpoint at six weeks of therapy. But it didn’t miss by much, and the low dose did score at a couple of other time points in the study, giving Allergan $AGN execs enough confidence to move the therapy into a major Phase III program.
Researchers put two doses of Botox — 30 units and 50 units — into the study, which recruited 258 patients. The 50-unit dose was a bust. But:
The treatment (LS mean for MADRS total score compared to placebo) difference for 30 U was -4.2 at 3 weeks (p- value 0.005); -3.7 at week 6 (p-value 0.053) and -3.6 at week 9 (p-value 0.049).
“I think the important thing in a Phase III environment is to increase the number of patients,” says Mitchell Brin, the CSO for Botox. You bring to bear a higher statistical power with less variability. And, he adds, “the data are still very fresh.” They can learn more things about this treatment as they continue to explore the results.
One other big difference between Phase II and Phase III, he adds, is that they will do away with the two different site networks used to test the 30 and 50 unit doses, which was required to keep the study blinded. And Chief Commercial Officer Bill Meury notes that if you consider the totality of all the mid-stage data now available, it’s reasonable to believe that Phase III — with more than one study needed for an approval — can achieve statistical significance.
EvercoreISI’s Umer Raffat wasn’t buying it, though. His comment:
So wait: is that a real signal or just noise for 30U?
– We know there is no dose response
– We know other endpoints like HAM-D are “numerically superior” – i.e., not statistically better
– We know trial sites did not overlap between 30U and 50U dose … perhaps 30U just got better sites?
So why would AGN announce that they are going into Ph 3 on the heels of this data?
My sense: Botox has some off-label sales in depression anyways … perhaps they don’t wanna jinx that near-term … and let a ph 3 go on for years to come
Maybe I am being too pessimistic here … but the data don’t read good on this one.
The data underscore that the treatment is active against the disease, insists Meury, “and if we can manage for placebo we have a good chance of having a successful trial.”
SSRI drugs are plentiful and will probably remain frontline therapies during our lifetimes, says Meury.
“This will be an alternative for people who can’t tolerate weight gain, sexual dysfunction or other adverse events,” he adds. But the benefit/risk ratio for Botox is very, very high, he adds. And the unmet medical need for this group of people remains high as well, making this the kind of product that can earn hundreds of millions of dollars each year, “at baseline.”
Allergan CEO Brent Saunders has been one of the most prolific dealmakers in biopharma over the past year, after its merger with Pfizer fell through. In this case, researchers were looking to see if they could nail down solid evidence of expanding the use of its wrinkle therapy for depression — which has proven to be one of the toughest targets in R&D.
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