Data Worsens For Arena’s Obesity Drug
study testing Arena Pharmaceuticals’ weight loss drug lorcaserin in
diabetic patients raises new safety concerns about the medicine, lowering
the odds that the Food and Drug Administration will ever approve it.
weight loss results were not impressive, but were statistically significant
and strengthen the case for the drug, which the FDA rejected last month.
The result in HbA1C, a measure of blood sugar, was better, showing a 0.5%
absolute reduction. That’s as much as Kombiglyze, the recently approved
diabetes pill from Bristol-Myers Squibb and AstraZeneca, lowered blood sugar
compared to an older drug, metformin.
those results are outweighed by the safety result, which shows more patients
on lorcaserin had heart valve problems, or valvulopathy, than those on placebo.
Valvulopathy has been the main safety worry for lorcaserin from the start,
because the drug was designed to hit the same receptor as the diet drug
fenfluramine, which was withdrawn because it caused heart valve damage.
From the release:
were performed at baseline and at Weeks 24 and 52. At Week 24, 2.5% of
lorcaserin 10 mg BID patients and 1.9% of placebo patients had new valvulopathy
(based on FDA criteria), and at Week 52, 2.9% of lorcaserin 10 mg BID
patients and 0.5% of placebo patients had new valvulopathy. BLOOM-DM was
not powered to detect meaningful differences in the incidence of valvulopathy.
what this means is hard to figure out, because Arena chose to present the
data in an opaque manner. Those percentages don’t seem to be taken
out of the total number of patients enrolled in the diabetes study (256
on lorcaserin twice a day and 300 on placebo) but instead the number of
patients who were still enrolled at 24 and 52 weeks. That means that we
can’t just figure out how many cases of valvulopathy and add them
to the existing database. I’ve asked Arena for more clarity.
really striking difference, between 2.9% and 0.5%, is probably due to the
play of chance in the small numbers of patients who were still enrolled
at the end of the study. But the problem is that, by a rigid statistical
test, Arena’s much bigger trials did not completely exclude the possibility
that lorcaserin carries a heart valve risk, as was discussed by a panel
of FDA experts before the drug was rejected. In its two big trials, based
on a note from analysts at Jefferies earlier this year, there were 58 cases
of valvulopathy in 1553 patients on lorcaserin and 51 cases among 2398 patients
if I make some favorable assumptions for Arena – mainly that a lot
of patients dropped out – it looks to me as if the gap between lorcaserin
and placebo increases. Messy, back of the envelope calculation: Assume that
there were 200 patients in the active group at 24 weeks and 150 patients
at 52, and 250 patients were on placebo at 24 weeks and 200 at 52, and you
get something like 9 cases of valvulopathy on lorcaserin and 6 on placebo.
If more patients stayed in the study, those numbers go up.
probably means that valvulopathy risk will get harder to rule out. Given
the relatively low efficacy of lorcaserin, this makes approval more challenging,
even if Arena can allay all of the FDA’s other worries. Without more
information, it’s hard to know exactly how big an issue this is, but
it is bad news.
is walking a tightrope. Without really strong efficacy, any safety worry
can tip the scales against it.