Feuerstein's Biotech-Stock Mailbag

Here's my rub: I don't think Isis has the safety data yet from mipomersen clinical trials to clear up all the concerns linking mipomersen to dangerous liver toxicity. Yes, I know, there was more data shown at Tuesday's analyst meeting downplaying such a risk, but it's not really enough. Not yet.

The FDA takes liver toxicity very seriously. It's one of the few safety risks that can basically stop a drug's development dead in its tracks. If you've never seen this, download and read the FDA's guidance on drug-induced liver toxicity. It's good information to have.

I'd be more favorably inclined toward Isis if it was developing mipomersen solely as a life-saving drug for the small number of people who have a genetic defect causing astronomically high cholesterol levels. In this orphan population, many of whom die prematurely, the risk-benefit of mipomersen is compelling, even with the risk of liver toxicity.

Isis could be another Genzyme(GENZ Quote), pricing mipomersen extremely high to treat relatively few patients, but still generating hundreds of millions of dollars in revenue annually.

But Isis has decided that mipomersen is destined for ordinary folks with uncontrolled cholesterol and a high risk for heart attack. For these people, Pfizer's Lipitor isn't working and they need something else. According to Isis, there are 15 million to 16 million patients in this category, which has the potential to generate $2 billion to $4 billion in mipomersen sales.

I understand why Isis would want to attack such a big market opportunity, but the risk-benefit equation is much different with this group of patients. The FDA is going to be way more conservative when it comes to safety.

Likewise, I suspect that any potential Big Pharma partners will also be wary of stepping into a drug that has the potential to cause serious liver injury. We all know that Big Pharma has a history of being seduced by biotech drugs with questionable efficacy, but how many times does Big Pharma pay up to license a drug that has questionable safety?

Not often, in my opinion. Not, at least, until the risks are better identified.

The recent boasts of Isis CEO Crooke may come to pass. He may just have a Big Pharma partner in his pocket, waiting to pay serious coin for mipomersen. I totally understand investors taking a flyer on Isis for that opportunity.

But do it with eyes wide open, and with the full understanding that: 1) expectations for a partnership are priced into the stock already, to some extent; 2) mipomersen is not out of the woods when it comes to liver toxicity; and 3) Crooke's long track record of antisense drug failure and disappointment doesn't entitle him to a free pass just yet.