Isis: Liver enzymes up in 7 pct of mipomersen group

* 6 patients, 7 pct of total, had increased liver enzymes

* No signs of liver dysfunction

* Injection reactions, flu symptoms common side effects

LOS ANGELES, Sept 1 (BestGrowthStock) – Seven percent of clinical
trial patients treated with Isis Pharmaceuticals Inc’s (ISIS.O: )
experimental cholesterol drug mipomersen developed elevated
liver enzymes, causing three of them to drop out of a pivotal
study, researchers said on Wednesday.

Isis, which is developing the drug with Genzyme Corp
(GENZ.O: ), said that of the 83 patients treated with mipomersen,
73 completed the trial.

In addition to the three drop outs related to elevations in
liver enzymes, a further six were related to adverse events —
injection site reactions (2), non-cardiac chest pain (2),
injection site reactions and flu-like symptoms (1), and
constipation (1).

All 41 patients treated with a placebo completed treatment.

The most common side effects were injection-site reactions
— seen in 93 percent of mipomersen patients, compared with 42
percent of the placebo group — and flu symptoms, which were
seen in 49 percent of the mipomersen group and 32 percent of
placebo patients.

The companies had announced in February that the trial,
which involved patients with severe, inherited high
cholesterol, known as heterozygous familial
hypercholesterolemia, met its goals.

It found that patients taking mipomersen experienced an
average reduction in “bad” LDL cholesterol of 28 percent after
26 weeks of treatment, compared with an average increase of 5
percent for placebo patients.

The full results were presented at the European Society of
Cardiology’s Congress in Stockholm, Sweden.

Similarly robust results have been seen in other mipomersen
trials, but some analysts are concerned that the incidence of
elevated liver enzymes, which can be a sign of liver damage,
might restrict eventual sales of the drug.

Isis said six mipomersen-treated patients had persistent
increases in liver enzymes. As measured by MRI, mipomersen
patients had a median increase of 4.9 percent in liver fat,
compared with an increase of 0.4 percent for placebo-treated
patients.

None of the patients, including those who discontinued the
study, had changes in other laboratory tests to indicate liver
dysfunction.

The trial also found that patients treated with mipomersen
had a 26 percent reduction in apolipoprotein B compared with a
7 percent increase for placebo; a 19 percent reduction in total
cholesterol compared with a 4 percent increase for placebo; and
a 25 percent reduction in non-HDL cholesterol compared with a 4
percent increase for placebo.

“In all four of the phase 3 studies we have completed, we
have seen consistent and robust reductions in LDL cholesterol
and other atherogenic lipids that support our plan to initially
target homozygous and severe heterozygous familial
hypercholesterolemia patients,” Isis Pharmaceuticals Chairman
and CEO Stanley Crooke, said in a statement.
(Reporting by Deena Beasley; Editing by Dhara Ranasinghe)

Isis: Liver enzymes up in 7 pct of mipomersen group