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Jim Letourneau's Blog

Investing, Technology, Travel, Geology, Music, Golf. I think that covers it.

American Heart Association Meeting - 2010

This post is part 4 of a 16 part series of posts taken from the transcript of an interview I (JL) conducted with Resverlogix (RVX.TO) co-founders Dr. Norman Wong (NW) and Donald McCaffrey (DM).

What follows is a lengthy and candid interview about the history of Resverlogix, recent events at the American Heart Association meetings, and future plans for the company.

I'll be publishing two interview segments a day so not all of the links may be active if you are viewing this near the end of March 28-April 5, 2011.

  1. Background of Dr. Norman Wong

  2. Early History of Resverlogix

  3. HDL Biology

  4. American Heart Association Meeting - 2010

  5. CETP History

  6. Importance of HDL Type

  7. AHA ASSERT Trial Response

  8. ALTs

  9. Investor Reaction

  10. The Next 2 Years

  11. David vs. Goliath

  12. Alzheimer's Therapy Potential

  13. Upcoming Assure Trial

  14. Volatility of Resverlogix

  15. Resverlogix is Expanding

  16. More on the sell-off


Part 4

I (JL) interviewed Resverlogix (RVX.TO) co-founders Dr. Norman Wong (NW) and Donald McCaffrey (DM) in early December. What follows is a lengthy and candid interview about the history of Resverlogix, recent events at the American Heart Association meetings, and future plans for the company.

The transcript is quite lengthy so I'll be dribbling the content into a couple of posts/day over the next 8 days.

  1. Background of Dr. Norman Wong

  2. Early History of Resverlogix

  3. HDL Biology

  4. American Heart Association Meeting - 2010


So at the American Heart Association, where Merck was bragging about their 138% increase
in HDL, the media just gobbled it up. Great numbers. That 138% increase of filled HDL is
equivalent to collecting your garbage bags and leaving them in the house. You want new
garbage bags to take this garbage out. We have a 21% increase in production of new HDL
versus their 138% in previously filled HDL that is now forced by CETP inhibition to remain in
the system. That's not good for them.

JL: Do they measure that by mass, or by number of particles?

NW: You just measure by ELISA assays. The HDLs are pretty simple.

DM: It's pretty standard. HDLs . . . ApoA-1, which was our main endpoint, is way harder
to measure. And even in a key endpoint, we were P=.06. That means 94 times out of 100,
you're going to prove the same thing. Which we did prove successfully. 95 times out of 100
is considered very successful in science. That's the difference we faced last week.

JL: I'm not a statistician, but I know it's like, come on.

DM: Exactly. And the other thing is without those increases . . .

JL: How many decimal places . . .

DM: 0.01. Without the confirmed increase of ApoA-1, the domino effect could not have
happened. We couldn't have had a 21% increase in the alpha-1 particle if we didn't have
successful ApoA-1. So we knew our data was very good. It surpassed everything we told the
market it was going to do. Then Merck came out with this 138% HDL number, which HDL
wasn't even their endpoint. LDL was. And they just blew the market away. It was ridiculous.
The Merck 138% number was old information, three years old.

JL: When you saw the press come out so quickly and a lot of them were saying that RVX was
trying to lower numbers instead of raise numbers. They were really . . .

DM: They were awful.

NW: If you looked at the timing of the press release, they did not have the information when
it was written. They released at 9:01 in the morning. Our presentation wasn't until 11:14. So
they never looked at the data. All they saw was a press release of the American Heart
summary..

DM: Here's the one you're referring to. Cardiology Today. It's titled "Novel Drug Did Not
Significantly Reduce ApoA-1 Levels." That's the title of it.

NW: Yeah. So they had mistakes all over the place.

DM: Significantly reduced. (Wrong direction)

JL: Yeah. That's how they started in the morning, and then a couple hours
later . . .

DM: This is the news release from the top cardio clinic in the United States, 16 straight
years, verses this second title which was the title of the first media new release. “Cleveland
Clinicresearchers find that new drug may clear plaque from arteries. The drug enhances
ApoA-1, a protein found in good cholesterol.” Here's what Bloomberg wrote before our data
was even presented …

“Resverlogix Cholesterol Pill Fails to Boost De-Clogging Protein in Trial”

JL: Unreal.

DM: And so, asked to retract it, Bloomberg retracts by going,

"Resverlogix stock falls on news."

JL: There's no winning.

NW: It was media driven. . .

DM: So then the AHA panel presented the late breaking clinical trials. Dr Nicholls presents
our data and the American Heart Association designated a respondent. The AHA designated
respondent was the author of the Merck paper. That's like having me as the respondent for
the Merck paper. Then a Merck representative on the panel, the guy who presented Merck’ s
data, started in on this safety stuff, which by the way does not exist. We have a very safe
drug. Then he publicly states , "Oh, I wouldn't take that drug."

JL: Yeah, I remember that quote. It was nasty.

DM: And we're sitting there going, wow. I mean, unbelievable. And they're quoting that their
drug was extremely safe, and how should I word it here. Here it is. In their paper, New
England Journal, "There was no appreciable difference between the Anacetrapib group and
the placebo group in the percentage of patients with adverse events that were thought to be
related to study drug."

That's how they presented it. The previous page read, "Cholesterol levels of . . ." Let's
see. "As specified by the protocol, the study drug was discontinued in patients who had
an LDL cholesterol level of less than 25 milligrams per deciliter." So that's pretty low. Your
brain uses the most cholesterol of your body, about 20%. You get too low of LDL, the
bad cholesterol, and you're dead. So, it's brain food, it's cell food. Too much of it is not
good. Too little of it is fatal. So of less than 25% milligram per deciliter at two consecutive
measurements. This occurred in 142 patients in the Anacetrapib group, 17.6% of the trial
patients had to discontinue drug use. No adverse events?

NW: They never told the audience about that at AHA.

DM: No adverse events? And in placebo, one patient.

JL: That's just by designing the trial so that these people . . .

DM: Sure.

JL: Crafty. Very crafty.

NW: They actually put them in, but when they dropped below that, they kicked them all out.
So that's a very biased view of the data.

JL: Was that in the initial trial design, or did they change that?

DM: It was in the initial trial design.

NW: It was the initial trial design.

JL: It's just crafty . . .

DM: And it may be headed in a fatal direction? Okay. They listed any differences in deaths as
insignificant. The difference in death with Torcetrapib vs placebo was a significant 25% and
it was pulled from trials. Anacetrapib was insignificant but was 27.5% higher than placebo.

JL: Really?

DM: But the numbers did not show statistical significance, so they ignored it at AHA.
Of direct cardiovascular deaths, four on Anacetrapib, one on placebo. And they were
equal numbers treated. Not statistically significant. So will their drug go anywhere? It was
portrayed in the media that this is the next big drug, and actually I think it's now the next
big drug failure.

JL: Why would they go and push it that far?

DM: Pharma’s have done this before, they've been doing it for decades, and some of the older
dinosaur ones still believe they can push drugs through. The FDA's not going to be fooled.
Their announcement of their next trial was based on a four-year long trial with an endpoint
being revascularization, which is not an endpoint of the FDA's.

NW: That's not going to fly.

DM: Will they go in and do an intravascular ultrasound program to show plaque regression?
No. They refuse to. Why? Because it doesn't work for plaque regression. So why are we
compared to them?? They're going to be out there for a few years spending money and trying
to run trials, but I feel the bottom line is it's not going to go anywhere. In 18 to 24 months,
we'll be done. We will have our data that shows plaque regression. This article here in the
New England Journal shows that you can play these statistical games, and if you're a big
pharma, you can play the media. You cannot get that drug approved the way they're trying
to do it. And if it's not removing the plaque, so what if they did? But nonetheless, we are
going the clean, straight way. Do we get beat up on the way because we're the little guy?
Hell yes. But bottom line, we have the drug that removes the plaque.