Zitat von Magnetfeldfredyhttp://www.thestreet.com/story/11526558/1/fdas-review-of-are…
ADAM "FUCKSTEIN" fängt an , andere Töne anzuschlagen....
FDA's Review of Arena Pharma's Obesity Drug Sunnier Than
The FDA's review of Arena Pharmaceuticals'(ARNA_) weight-loss drug
lorcaserin is... and it's more positive than I expected
The outcome of Thursday's FDA advisory panel is still unknown, of
course, but Arena bulls (the "Areniacs") should feel more
confident in a positive vote recommending lorcaserin's
Arena shares are up 41 cents, or 15%, to $3.14 in recent
Arena's lorcaserin still doesn't help people lose much weight. A
300-pound person is going to lose about 9 pounds after a year of
treatment. But the efficacy hurdle for approval of an obesity drug
in the U.S. is low, so lorcaserin gets a pass. More important to
the outcome of Thursday's FDA advisory panel, the agency appears
to be relatively satisfied with lorcaserin's safety.
the issues that dogged the drug and caused it to be rejected in
2010 have been addressed, according to my interpretation of FDA's
briefing documents released today.
FDA seems less concerned about lorcaserin-fueled rat tumors and the
potential risk for breast cancers and other tumors in humans.
On the subject of mammry adenocarcinomas in rats, FDA reviewers
"Readjudication by the PWG allowed identification of a 24-fold
safety margin for mammary adenocarcinoma relative to the clinical
dose of 10mg bid lorcaserin. In general, the Agency interprets a
24-fold safety margin to a non-genotoxic carcinogen in rodents as
indicative of negligible risk to human subjects."
FDA did conclude that lorcaserin causes significant increases in
benign fibroadenomas in rats with no acceptable safety margin
relative to human doses, but the agency also downplays the
"Lorcaserin minimally effected plasma and tissue prolactin and
differentiation of mammary lobular structures in female rats in
mechanistic studies up to three months duration, but the changes
that were observed are consistent with hormonal action on mammary
tissue. No pattern of change was observed for estrogen,
progesterone, or luteinizing hormone, and the Agency is not aware
of a threshold of prolactin beyond which mammary tumors emerge.
Given the high sensitivity of SD rats to prolactin and the absence
of changes in other hormones, it is plausible that minimal
increases in prolactin induced by lorcaserin contributed to the
emergence of fibroadenoma in female rats."
On the question of whether lorcaserin's mechanism is "dirty" and
therefore may activate receptors known to cause heart valve damage,
FDA says this:
"The 2011 receptor potency data provides supportive evidence that
off-target activation of the 5HT2A or 2B receptors is unlikely at
the proposed clinical dose of lorcaserin (10mg bid). This is
consistent with neurological and cardiac assessments in animals
which did not identify major toxicities that would be anticipated
if 5HT2A and 2B were activated by lorcaserin. However, limitations
in neurological assessments and the lack of validated models for
drug-induced valvulopathy in animals preclude a definitive
prediction that lorcaserin will be devoid of such toxicities should
it be approved for marketing."
Still, concerns about lorcaserin's negative effect on heart valves
-- so-called valvulopathy -- remains. This is probably the most
significant risk going into Thursday's FDA panel because heart
safety data pooled from the three phase III studies trips a
statistical red flag for FDA.
"Nevertheless, in the pooled analysis of the Phase 3
echocardiographic data, the relative risk for FDA-defined valvular
heart disease (VHD), defined as mitral regurgitation greater than
mild or aortic regurgitation greater than trace was 1.16, with a
95% confidence interval (CI) of 0.81 to 1.67. This upper bound
exceeds the 1.5 upper bound requested by FDA to rule out an excess
risk of VHD. The point estimate and upper bound were similar in a
number of sensitivity analyses conducted by the sponsor and FDA
statistician. Furthermore, individual valve regurgitation was
fairly consistently increased in the lorcaserin treatment group.
Whether these findings can be explained by ascertainment or other
bias (due to greater weight loss in the lorcaserin group) is
And with all that, the odds of a positive vote at
Thursday's panel must go up.
I was at 30-40% last week
predicting a negative panel.
This morning, I'm at 60% odds
favoring a "yes" vote.
Lorcaserin appears to be a drug that will help enough people lose a
little bit of weight without causing too much harm. We can debate
whether such a drug is worthy of widespread use (I say no) but
in today's regulatory environment, this seems to be an
"approvable profile" for an obesity drug
The experts on FDA's advisory panel get to have their say on
Thursday. I will be live-blogging the proceedings all day, so
please tune in for the fun.