Biotech Values

[DewDiligence]

Re: ISIS ALT elevations

>I am surprised you didn't comment about this. I don't believe the drug could get approved or a partnership deal signed with the alt elevations observed.<

The only reason I didn’t comment on the ALT elevations is that it’s old news. See, for instance, message #37415 from November (#msg-14794270):

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In Isis' press release, it stated the drug demonstrated a strong safety profile and was well tolerated. But one area investors should keep a close eye on is liver toxicity. The threshold of liver function that is usually cited during the testing of drugs is three times the upper limit of normal (ULN) of the enzyme ALT. Drug companies don't want to see their test subjects go above three times ULN. Of the 40 patients who received the drug, two experienced greater than three times ULN, while eight fell into the two-to-three-times ULN category.

Isis CEO Dr. Stanley Crooke stresses that readings were taken on a weekly basis (vs. monthly in other studies) and that it's more important to look at the figures compared with the numbers of readings (roughly 1,100) vs. the number of patients. He adds, "If you take the average person off the street and run liver enzymes on them weekly, over a period of three months, you will find multiple times when their liver enzymes might be up."

The Street seems to buy into this line of reasoning. However, not everyone is taking the numbers at face value. One hedge fund manager who is short Isis and requested anonymity counters the CEO's argument, stating, "The incidence of ULN readings increases significantly at higher doses, which is evidence that suggests a drug effect."

He says it's important to note that liver toxicity is a cumulative effect, and that is why he's particularly interested in the two-to-three-times ULN numbers, considering that the trials were short -- five weeks and three months of dosing.

Comparatively, phase III trials for cholesterol fighters such as Bristol-Myers Squibb's (BMY) Pravachol, Merck's (MRK) Zocor and Pfizer's (PFE) Lipitor involved thousands of patients over a longer time period. Since high cholesterol is a chronic condition, the money manager is concerned that with readings already in the two-to-three-times ULN category after such a short time, more patients may cross the threshold with continuous use of ISIS 301012.
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I don’t have a strong opinion about whether this is enough to stop a partnership deal from being consummated. What we do know is that ISIS is anxious to get one signed before starting phase-3.

The CC Tuesday morning may provide a better feel for how this will shake out.