You could hear a pin drop. Shareholders of Resverlogix waited with baited breath for November 17th. That was the day that Resverlogix President and CEO Donald McCaffrey was to present data from the company’s ASSURE trial. In that study, which was completed earlier this year, just under three hundred patients with coronary artery disease took Resverlogix’s treatment, RVX-208, designed to promote the production of HDL, or good cholesterol. RVX-208 is oral small molecule drug that works by increasing serum levels of ApoA-l, a key cardioprotective protein that makes up 70 percent of HDL cholesterol.
Shares of Resverlogix had rallied to a high of $6.39 on November 15th, more than three dollars higher than they had been in August. But shareholders felt the AMA meetings delivered the worst possible news: Resverlogix shares tumbled when it was reported that the company delivered less than stellar results. The “drug had modest efficacy, but it came with safety concerns,” said Simos Simeonidis, an analyst with Rodman & Renshaw. What was worse was that Merck reported results with a competitive drug that showed what some referred to as “jaw dropping” results. Merck’s anacetrapib increased good HDL levels by 138 percent after 24 weeks of treatment, and lowered levels of bad LDL cholesterol by 40 percent in patients already taking LDL-lowering statins. But were the results of the AHA meeting that black and white? Donald McCaffrey, President and CEO of Resverlogix thinks investors overreacted in the days since, which have seen shares of Resverlogix tumble to a low of $1.89 on November 24th. Donald talked to Cantech Letter about his take on the AHA conference and the subsequent reaction.
Donald, Shares of Resverlogix tumbled after the AHA meeting. Do you feel this was an overreaction?
Most certainly! Big numbers by big pharma completely confused the media covering the event, media completely ignored the fact that Resverlogix science results surpassed expectations. This was also the view the researchers at the Cleveland Clinic, the top cardiovascular facility in the USA for the past 16 straight years. The title of the Cleveland Clinic news release (the trial investigators) regarding the Resverlogix results read as follows; “CLEVELAND CLINIC RESEARCHERS FIND THAT NEW DRUG MAY CLEAR PLAQUE FROM ARTERIES- The Drug Enhances ApoA-I, a Protein Found in “Good” Cholesterol”, while the lead major US media article was titled as follows: “Resverlogix Cholesterol Pill Fails to Boost De-Clogging Protein in Trial. Clearly the Cleveland Clinic investigators know what their results where and the media coverage completely missed the point.
A report issued by Dundee Securities on November 22nd noted that Merck’s new drug anacetrapib “comes from a drug class (CETP inhibitors) that has failed in the clinic”, and that, in 2006, Pfizer terminated development of a similar drug It seems there is still a long way to go for both RVX-208 and for Merck’s Anacetrapib. Do you feel, recently, investors are treating this as a sprint when it is really a marathon?
Drug development of any kind is always a marathon and never a sprint as it is the most highly regulated business on the planet. The CETP class of drugs approaches development from a completely different point of development as does Resverlogix. The only program in development that is designed to show plaque regression in the arteries is the ASSURE trial being planned by Resverlogix. The Merck CETP program has chosen to avoid needing to show plaque regression. The Resverlogix plaque regression program should have conclusive data in place within 18 to 24 months whereas the recently announced Merck program will take at least four years and will not show any form of plaque regression.
Is it useful to compare the trials and progress of RVX-208 that anacetrapib or is this a dangerous practice?
It would be extremely useful to see a fair comparison of the two approaches. Currently too many groups simply look at the large HDL Merck number vs the seemingly lower Resverlogix HDL number. The difference in how they are attained makes all the difference and this fact is offen ignored. In the CETP case the HDL increases are due to the CETP drug stopping a filled HDL molecule from leaving the body. In Resverlogix case the HDL is functional new HDL that is empty and yet to fill up with unwanted plaque residing in the patients arteries. 21% increase in new, unfilled HDL, far exceeds a 100% increase in HDL that represents already filled filled HDL molecules. Our approach should be able to prove that it can remove plaque from the arteries and the other program has chosen not to even try to determine if it does. This is a case where quality far out strips quantity.
Can you comment on how RVX-208 affects liver enzymes? Was the raise in the level a surprise to you or did you expect this because the drug functions in the liver? Are there any toxicity risks to RVX-208?
The liver enzymes that you are referring to are often misunderstood. What we saw in the ASSERT trial was not only expected but if we are right regarding our approach it is very much wanted. What we saw in the trial was an increase in an enzyme referred to as an ALT. The false assumption that has been made is that all ALT markers are negative, not so. A signal of liver injury would be only if bilirubin was also increased. We have never had a case of bilirubin or other true liver injury markers. ALT’s are merely a signaling mechanism that highlight a change is happening. The change can be liver injury, only if bilirubin increases, however the change can also be a strong signal that more plaque is being flushed from the arteries through the liver. Our increases are at the same point in time that the drug is functional and the highest of those few that we see also correlate with the highest increases in large particle HDL increases. The large particle HDL increase is also the final signal that plaque is being removed from the arteries. This is our, and always has been our, overall goal.
Do the results you talked about at the AHA meeting change the capital requirements of Resverlogix?
We will proceed with our next trial – our Phase 2b IVUS (intravascular ultrasound) study – with recruitment starting in Q1 2011. Capital requirements remain the same and when it is appropriate we will eventually seek another financing either through the markets, a draw down on the SEDA or with a pharma partner.
Can CETP remove plaque in humans?
If it can then I would think that a pharmaceutical company would run a simple 6 to 12 month clinical trial, costing less than $20MM. However as it is the case with Merck, they just announced a 4 year clinical trial at a cost of hundreds of millions and they stated they are not looking at plaque regression.