UPDATE: Genzyme, Isis Cholesterol Drug Data Raise Questions
May 20 2009 - 12:45PM
Dow Jones News
Genzyme Corp. (GENZ) and Isis Pharmaceuticals Inc. (ISIS)
reported the success of a late-stage trial of cholesterol treatment
mipomersen, but Wall Street is worried that side effects could
reduce its potential in broader populations, cutting sales by
hundreds of millions of dollars.
The companies said mipomersen cut so-called bad cholesterol
levels by 25% in patients with homozygous familial
hypercholesterolemia, a rare genetic disorder of severely elevated
cholesterol that affects only a few hundred people in the U.S. The
results should help secure regulatory approval, but the study's 18%
dropout rate among the severely ill patients suggest less-severe
patients aren't as likely to use the drug.
"That calls into the question the ability to develop the drug in
the larger market opportunities," said Leerink Swann analyst Joseph
Schwartz.
The worries comes from elevated liver transaminases, a signal of
liver damage, being one of the most common side effects that caused
one patient to drop out and could raise questions from regulators.
Other patients left the study because of injection-site reactions,
rashes, non-compliance and personal reasons.
The dropout rate was surprising because patients in the study
have extremely high cholesterol that doesn't respond to typical
therapies. They often have had cardiovascular events and face
significantly shortened lives, which makes their decision to stop
using the drug alarming.
Isis shares, up 33% before today from their March 5 low, fell 6%
Wednesday to $14.54 on more than twice its average daily
volume.
Schwartz said the drop in the stock is "not very much
considering the severity of the dropouts" and the implications for
the future use of the drug.
Genzyme has touted the potentially huge target number of
patients that could use mipomersen, alluding to annual sales
eventually reaching $2 billion.
It would be a long road to get to that population. JPMorgan
analyst Geoffrey Meacham projects a relatively modest market for
homozygous familial hypercholesterolemia with 550 to 600 patients
in U.S. and Europe paying about $200,000 a year.
"We have a difficult time modeling much more than $100 million
in [annual] sales," he said.
Genzyme partnered with Isis in early 2008 with an upfront
payment of $325 million, an unusually large payment for a drug that
had no late-stage data at the time. The deal also includes more
than $1.5 billion in potential milestone payments to Isis that are
backweighted to its later success.
Any problems in getting the drug to wider populations could
significantly alter those payments, thus impacting the market
valuation of Isis.
Mipomersen cuts production of a protein critical to the
production and transport of low-density lipoproteins, or LDL, often
called bad cholesterol. It is intended for patients who are unable
to achieve target cholesterol levels with drugs known as statins
alone or who are intolerant of statins.
In the study, patients had a baseline LDL of more than 400
milligrams per deciliter of blood despite being on the maximum
amount of lipid-lowering therapies. The American Heart Association
describes LDL under 100mg/dl as "optimal" and above 160mg/dl as
"high."
Regardless of any impact on wider sales, Wall Street is
generally expecting mipomersen to be approved for these niche
patients that have few alternative options.
The companies reiterated their expectations to file for
marketing approval in the second half of 2010, based on these
data.
-By Thomas Gryta; Dow Jones Newswires; 201-938-2053;
thomas.gryta@dowjones.com