Biotech Values

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From BioWorld Today. I can't believe what he said at the end:

In regard to the fi rst issue, diagnostic uncertainty in the
classifi cation of mammary masses in female rats, “some of the
preliminary tissue diagnoses for mammary tumors differed
from the fi nal diagnoses in the study report,” noted Christy
Anderson, vice president of lorcaserin development. “In
particular, some mammary tumor types were recharacterized
from benign to malignant, and vice versa.”

The company has convened a group of fi ve independent
pathologists to review the relevant tissues from the rat
carcinogenicity study and to readjudicate the diagnoses
of female rat mammary tumors in a blinded fashion, as
requested by the agency, which has reviewed and approved
the protocol, Anderson said.

The second nonclinical issue was an unresolved
exposure-response relationship for lorcaserin-emergent
mammary adenocarcinoma. The FDA has asked Arena to
demonstrate the mechanism by which lorcaserin causes
mammary tumors in rats and to demonstrate that this
mechanism is “reasonably irrelevant” to human risk,
Anderson said. The company maintains that lorcaserinmediated
increases in serum prolactin explain the risk
for malignant breast tumors – a fi nding that would be
“reasonably irrelevant to human risk,” Anderson said, adding
that the FDA has previously accepted this mechanism
for other drugs. Arena has initiated nonclinical studies
to provide evidence that demonstrates clear, persistent
increases in prolactin in intact female rats at doses of
lorcaserin associated with mammary tumors in rats.

“The FDA hasn’t asked us to demonstrate tumors in
rats,” Anderson added. “They’ve only asked us to show a
convincing increase in prolactin in response to lorcaserin.”

The third nonclinical issue was an unidentifi ed mode of
action and unclear safety margin for lorcaserin-emergent
brain astrocytoma – cancer that occurred in male rats who
received the highest dose of lorcaserin. In the absence of
information about the mechanism in which these tumors
form, the FDA has asked Arena to clarify the safety margin
in rats, relative to humans. The company has initiated
several nonclinical experiments and plans to initiate a small
clinical study to enroll approximately 10 volunteers who will
be dosed with lorcaserin for about one week, followed by
parallel cerebrospinal fl uid and blood collection.
“Although lorcaserin cannot be readily measured in
the human brain, the concentration in cerebrospinal fl uid,
which can be measured, will provide an additional estimate of brain levels,” Anderson said.

In short, the FDA has accepted Arena’s explanation of
the controversial rat data, Lief maintained. “We just have to
show them the data,” he told BioWorld Today.